ORGANIC CHEMISTRY

FRONTIERS

View Article Online

REVIEW View Journal | View Issue
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

Recent advances in the photocatalytic cleavage of

Cite this: Org. Chem. Front., 2025,
C–C and C–N bonds associated with amines and
12, 975 their derivatives
Qibo Ni, Yan Zhou, Lang Chen and Yunkui Liu *

The cleavage of C–C and C–N bonds in ubiquitous amines and their derivatives serves as an important
and useful protocol for the construction of valuable organic molecules. Recently, the visible-light-driven
photocatalytic strategy for C–C and C–N bond scissions has received much attention because such a
strategy has characteristic advantages of mild reaction conditions, unique selectivity and environmentally
Received 31st October 2024, benign operation in comparison with the traditional thermal reaction protocols. In this review, the recent
Accepted 20th November 2024
advances in the visible-light-mediated photocatalytic cleavage of C–C and C–N bonds associated with
DOI: 10.1039/d4qo02038c amines and their derivatives are summarized. At the end of this review, the limitations and challenges in
rsc.li/frontiers-organic this field are pointed out, and the future research direction of this field is also discussed.

1. Introduction their derivatives play an extraordinarily significant role in aca-

demia and industry.
Amines ( primary, secondary, and tertiary) are widely found in The cleavage and formation of chemical bonds has been
natural products, pharmaceuticals, biomolecules, and func- the core of discussion since the beginning of organic chem-
tional materials.1 They are easily available from natural istry. Compared with the cleavage of chemical bonds with low
sources as well as artificial synthesis.1,2 Thanks to the versatile dissociation energies (such as the C–Br/I bond),3 the cleavage
synthetic platform based on amines, they can be easily con- of C–C4 and C–N5 bonds, which have shorter bond lengths
verted to a wide range of functionally and/or synthetically valu- (also have higher dissociation energies) and are not easily
able N-containing compounds, such as imines, amides, qua- polarized, is a more challenging task. Therefore, chemists are
ternary ammonium compounds, Katritzky salts, azo- and diazo committed to achieving the cleavage of C–C and C–N bonds
compounds, isonitriles, N-heterocycles, etc. Both amines and through various means. To date, the cleavage of C–C bonds
has been mainly achieved by three traditional thermochemical
strategies: (a) activation of C–C bonds through transition
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology,
metal-catalyzed oxidative addition processes,4b,6 (b) β-carbon
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou
310014, China. E-mail: [email protected]
elimination,7 and (c) the metal-mediated retro-allylation

Qibo Ni was born in Zhejiang Yan Zhou was born in Zhejiang

Province (China) in 1999. He Province (China) in 2000. In
received his bachelor’s degree 2022, she received her bachelor’s
from Huzhou University in 2021. degree from Hangzhou Normal
Then, he started his graduate University. She continued to
research at the Zhejiang pursue her master’s degree at
University of Technology under Zhejiang Technology University
the supervision of Prof. Yunkui under the supervision of Prof.
Liu. His research interests focus Yunkui Liu. Her main research
on P/N-heteroleptic Cu(I)-photo- interest focuses on P/N-heteroleptic
sensitizer-catalyzed radical reac- Cu( I )-photosensitizer-catalyzed
tions. radical reactions.
Qibo Ni Yan Zhou

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 975
 View Article Online

Review Organic Chemistry Frontiers

process.8 As for the cleavage of C–N bonds, it is often necess-

ary to pre-activate the bonds, such as by conversion into
iminium,9 diazonium,10 quaternary ammonium11 and pyridi-
nium salts (Katritzky salts).12 Despite significant progress
being made in the field of C–C and C–N bond scissions, it can
be seen that the cleavage of C–C4,6–8 and C–N5,9–12 bonds
under thermal reaction conditions often requires relatively
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

harsh reaction conditions, complicated pre-treatments, and/or

expensive and toxic transition metal catalysts. With a growing
emphasis on resource and energy conservation and environ-
mental concerns,13 the development of novel and efficient
methods that allow for the cleavage of C–C and C–N bonds
under mild and environmentally friendly reaction conditions
has become a desirable synthetic target to achieve in synthetic
chemistry.
In the past two decades, with the renaissance of radical
chemistry, visible-light-mediated photocatalysis has emerged
as an efficient and powerful tool for the construction of mole-
cular complexity because of its unique activation mode via the
combination of photosensitizers and visible light.14 Such an Scheme 1 Various reactivities of amines under visible-light-driven
activation mode facilitates various sustainable free-radical- photocatalysis conditions.

mediated processes wherein the cleavage and formation of

chemical bonds can be achieved under relatively mild reaction
conditions, with unique selectivity and broad functional group quenching mechanism.14e,16 In these cases, amine additives
tolerance. As a result, recently, more and more elegant photo- are merely used as quenching agents for the completion of a
catalytic reactions involving the cleavage of inert chemical photocatalytic cycle wherein they themselves are not incorpor-
bonds,11d,12d,e,15 certainly including the cleavage of C–C15a–d,k,l ated into the final products (Scheme 1a). In addition, some ter-
and C–N11d,12d,e bonds associated with amines and their tiary amines can be utilized as useful HAT (hydrogen atom
derivatives, have been documented in the literature. transfer)17 or XAT (halogen atom transfer)18 agents upon con-
Actually, the reactivity of amines has long been a hot version into radical species under visible-light-driven photo-
research topic in visible-light-mediated photocatalysis. Amines redox reaction conditions. In these cases, amines also do not
can play different roles in photocatalytic reactions according to engage in the reassembly process with substrates (Scheme 1b).
their different reactivities. For example, tertiary amines (mostly Moreover, amines can be utilized as reductants for quenching
Et3N and iPr2NEt) have been proved to be faithful partners of photocatalysts as well as precursors for the generation of
excited photocatalysts for serving as electron sacrificial agents, nucleophilic α-aminoalkyl radicals that are capable of reacting
especially in those photocatalytic reactions via the reductive with various electrophilic reagents.19 Alternatively, they can be

Lang Chen received her bache- Yunkui Liu is a professor

lor’s degree from the Hunan at the Zhejiang University of
University of Arts and Science in Technology. He received his PhD
2022. She is currently pursuing degree (2002) in organic chem-
her master’s degree at the istry from Zhejiang University
Zhejiang University of Technology (China). He then studied at
under the supervision of Prof. Hokkaido University (Japan) as a
Yunkui Liu. Her main research JSPS/JST postdoctoral fellow
interest focuses on late-transition- (2002–2005) supervised by pro-
metal-catalyzed reactions includ- fessor Yasushi Tsuji. He was a
ing P/N-heteroleptic Cu(I)-photo- visiting scholar at the University
sensitizer-catalyzed reactions. of California at Santa Barbara
Lang Chen Yunkui Liu (USA) (2017–2018). His current
research interests focus on late-
transition-metal-catalyzed highly selective reactions, including
P/N-heteroleptic Cu(I)-photosensitizer-, homogeneous Au(I)-, and
other late-transition-metal-catalyzed reactions.

976 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

used as two-electron donors to reduce photocatalysts as well as

precursors for the generation of electrophilic iminium cations
that are capable of reacting with various nucleophilic
reagents.20 Under these two reactivity scenarios, amines par-
ticipate in the reassembly process with substrates, but no
occurrence of C–C and/or C–N bond scission events associated
with them is involved (Scheme 1c). Finally, upon treatment
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

under visible-light photoredox reaction conditions, amines

can also undergo C–C and/or C–N bond scission reactions,
thereby enabling the generation of various reactive species
(Scheme 1d).11d,12d,e,15a–d Compared with the traditional
thermal reactions of C–C4 or C–N5 bond scission, such photo-
catalytic variants via free-radical-induced fragmentation can
generally proceed under mild conditions and have therefore Scheme 3 Different types of C–N bond scissions associated with
become a promising and attractive alternative strategy for the amines and their derivatives under photoredox conditions.
cleavage of C–C or C–N bonds. In recent years, great progress
has been made in this field. Under this context, we would like
to contribute a review on the recent advances in the visible- under each subcategory, the detailed progress associated with
light-mediated photocatalytic cleavage of C–C or C–N bonds different classes of amines and their derivatives will be
associated with amines and their derivatives. Since the photo- discussed.
catalytic cleavage of C–C bonds associated with cycloalkyla-
mines (cyclopropylamines and cyclobutylamines)15a,d and
Hantzsch esters21 has been previously summarized in several 2. Photocatalytic cleavage of C–C
reviews, only the representative and very recent examples bonds
associated with these two types of compounds will be dis-
cussed in the present review. Besides, since several reviews 2.1. Amino radical cation species-induced cleavage of Cα–Cβ
have previously highlighted the photocatalytic cleavage of C–N bonds
bonds associated with Katritzky salts12d,e and quaternary Under photoredox catalytic conditions, the lone-pair electrons
ammonium compounds,11d the photocatalytic reactions con- of N-atoms in amines and their derivatives may easily undergo
cerning these two types of amine derivatives are not covered in a single electron transfer (SET) process with excited photocata-
this review. We hope that this review could provide a quick lysts, leading to the formation of amino radical cation species.
overview of the state-of-the-art advances in this flourishing Such an amino radical cation species is prone to inducing the
field to related researchers, help them better understand the cleavage of the Cα–Cβ bond, especially if there is a highly
future development trend, and facilitate the design of innova- strained alicyclic ring or a leaving group at the β-position to
tive photocatalytic reactions. the N-atom, resulting in the formation of a cationic species
To compile this review more concisely, the content is first along with a radical species (or a distonic radical cation in the
introduced according to two different main categories of case of cycloalkylamines) (Scheme 2a, vide supra). Both the
chemical bond scission: C–C bond cleavage and C–N bond resulting cationic species and the radical intermediate may
cleavage. Then each category is further divided into several serve as reactive intermediates for various chemical transform-
subcategories according to different bond-scission types which ations. In this section, we will introduce some representative
are illustrated in Schemes 2 and 3, respectively. Furthermore, examples associated with different types of amine derivatives,
including cycloalkylamines (cyclopropylamines and cyclobutyl-
amines), tertiary amines, and N-heterocycles.
2.1.1 Amino radical cation species-induced cleavage of Cα–
Cβ bonds in cycloalkylamines. Cyclopropylamines and cyclo-
butylamines belong to small ring compounds, and they are
prone to undergoing irreversible opening of their ring via clea-
vage of the Cα–Cβ bonds upon SET oxidation to the nitrogen-
centered radical cation species under visible-light photoredox
conditions, leading to the formation of active β-carbon radical
iminium ions and γ-carbon radical iminium ions,
respectively.15a,d The resulting distonic radical cations are ver-
satile building blocks for a variety of dipolar cycloaddition
reactions.22 For instance, in 2012, the Zheng group for the first
Scheme 2 Different types of C–C bond scissions associated with time reported a Ru(bpz)3(PF6)2-catalyzed intermolecular [3 + 2]
amines and their derivatives under photoredox conditions. cycloaddition of cyclopropylamines 1 and olefins 2 to access

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 977
 View Article Online

Review Organic Chemistry Frontiers

aminocyclopentane derivatives 3 with high regioselectivity

under visible-light-driven photocatalysis conditions
(Scheme 4).23 Regarding the mechanism, first, the reaction
starts with the generation of amine radical cation 4 through
the SET oxidation of cyclopropylamines 1 by the excited Ru(II)-
photocatalyst. A key radical-induced β-fragmentation leads to
the three-membered ring opening and the formation of
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

β-carbon radical iminium ion 5. Then the [3 + 2] cycloaddition

of 5 with styrene 2 delivers an N-centered radical cation 6.
Finally, an SET reduction of 6 by the reductive Ru(I) species
affords the target product 3 and regenerates the Ru(II)-photo-
catalyst. The reaction exhibits excellent regioselectivity and
broad functional group tolerance under mild reaction con- Scheme 5 Visible-light-driven cleavage of the Cα–Cβ bond in cyclo-
butylamines and a related [4 + 2] cycloaddition reaction with olefins.
ditions. In addition, Zheng et al. found that the intermolecular
[3 + 2] cycloaddition of bicyclic tertiary cyclopropylamines 7
and olefins 8 could also proceed smoothly to give 5,5-fused
bicyclic heterocycles 9 with high diastereoselectivity and good pentene derivatives including methylsulfonyl-, arylsulfonyl-,
substrate compatibility. chloro-, ester- and trifluoromethyl-functionalized ones
Similarly, cyclobutylamines can also undergo the cleavage (Scheme 6).25 The authors disclosed that this cycloaddition reac-
of the Cα–Cβ bonds upon conversion to the nitrogen-centered tion proceeds through the reductive quenching catalytic cycle
radical cation species, although in this case, Ir( ppy)2(dtbbpy) rather than the oxidative quenching catalytic cycle based on pre-
PF6 is a more effective photocatalyst than Ru(bpz)3(PF6)2 and liminary mechanistic experiments and DFT calculations.
more strong irradiation conditions are required.24 The result- Since Zheng’s pioneering research work on the photo-
ing γ-carbon radical iminium ions serve as versatile 1,4-dipolar catalytic intermolecular [3 + 2] cycloaddition of cyclopropyl-
synthons to react with various π-unsaturated molecules for the amines with olefins to access pharmaceutically valuable cyclo-
convenient construction of synthetically valuable six-mem- pentylamine derivatives,23 recently, several asymmetric var-
bered ring compounds (Scheme 5). iants for the synthesis of chiral cyclopentylamine derivatives
Despite having regioselectivity problems in the annulation have also been successfully achieved by using different plat-
of cyclopropylamines with internal π-unsaturated systems,15d forms of photocatalysts and chiral catalysts (Scheme 7).26 For
in 2022, the Liu group reported a P/N-heteroleptic Cu(I)-photo- instance, in 2020, Ooi and co-workers for the first time
sensitizer-catalyzed regiospecific [3 + 2] annulation of cyclo- reported a highly diastereo- and enantioselective [3 + 2] cyclo-
propylamines with various functionalized alkynes, leading to addition of N-cyclopropylureas with electron-neutral olefins
the divergent construction of useful functionalized 3-aminocyclo- enabled by a chiral ion-pair photocatalyst which comprises a
polypyridyl Ir(III) cation and a weakly coordinating chiral
borate anion (Scheme 7a).26a The key to inducing chirality
relies on the use of urea as a redox-active anion-recognizable
directing group and the iridium-chiral borate ion-pair
[Ir(III)][B] as a photocatalyst. Later, the Ooi group further

Scheme 6 Visible-light-driven P/N-heteroleptic-Cu(I)-photosensitizer-

Scheme 4 Visible-light-driven cleavage of the Cα–Cβ bond in cyclo- catalyzed regiospecific [3 + 2] cycloaddition of cyclopropylamines with
propylamines and a related [3 + 2] cycloaddition reaction with olefins. functionalized aryl alkynes.

978 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

Despite much progress being made in the intermolecular [3 + 2]

cycloadditions of cyclopropylamines with olefins,15a,d,23b,c,26
in sharp contrast, the intramolecular [3 + 2] cycloaddition
variants have been underexplored. In 2019, Stephenson
and co-workers reported a rare example of [Ir(dF(CF3)
ppy)2(dtbbpy)]PF6-catalyzed intramolecular [3 + 2] photocy-
cloaddition involving alkene-tethered aminocyclopropanes for
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

the efficient and convenient synthesis of 1-aminonorbornanes,

which can serve as useful aniline bioisosteres (Scheme 8).27
Mechanistically, the homolytic C–C bond cleavage in the
amine radical cation intermediate triggers the consecutive 6-
exo-trig and 5-exo-trig radical cyclizations to obtain the norbor-
nane core structure. This strategy is one of the most effective
and flexible methods for the preparation of 1-aminonorbor-
nanes, which has advantages of excellent functional group tol-
erance and gram-scalable continuous-flow synthesis.
In 2022, Stephenson’s group further explored an intra-
molecular [3 + 2] photocycloaddition involving alkene-tethered
cyclopropylsulfonamide derivatives for the convenient con-
struction of a 2-azanorbornane scaffold enabled by an acridi-
nium organophotocatalyst (Scheme 9).28 Similar to the above-
Scheme 7 Several visible-light-mediated asymmetric variants of [3 + 2] mentioned protocol for the synthesis of 1-aminonorbornanes,
cycloaddition of cyclopropylamine derivatives with olefins. this cycloaddition also initiates from the homolytic Cα–Cβ
bond cleavage in the cyclopropylamine radical cation inter-
mediate followed by an intramolecular 6-exo-trig radical cycli-
expanded this strategy for the asymmetric synthesis of five- zation to give the target products. Notably, the added Lewis
membered alicyclic α-quaternary β-amino acids via the chiral acid plays an important role in facilitating the ring-opening of
[3 + 2] cycloaddition between cyclopropylureas and electron- the cyclopropylamines.
deficient α-substituted acrylates (Scheme 7a).26b In 2020, the Besides being susceptible to [3 + 2] cycloaddition with
Huang and Jiang group realized an asymmetric [3 + 2] cyclo- π-type dipole systems, cyclopropylamines also allow for cyclo-
addition of cyclopropylamines with α-branched 2-vinylazaar- addition with σ-type dipole partners. In 2022, Molander et al.
enes to furnish chiral azaarene-substituted cyclopentanes reported a photoinduced [3σ + 2σ] cycloaddition of cyclo-
enabled by cooperative DPZ photoredox catalysis and chiral propylamines with bicyclo[1.1.0]butanes to efficiently access
Brϕnsted acid catalysis (Scheme 7b).26c The use of rigid and trisubstituted bicyclo[2.1.1]heptanes, which may serve as
confined C2-symmetric imidodiphosphoric acid catalysts plays useful meta-substituted arene bioisosteres, in a sustainable
a key role in the achievement of high enantio- and diastereo- and straightforward manner (Scheme 10).29 In the radical
selectivities in the transformations. Using similar cooperative cyclization process, the selective homolytic cleavage of the
photoredox and asymmetric H-bonding catalytic systems, in C1–C3 σ-bond in bicyclo[1.1.0]butanes is the key factor to guar-
2022, Jiang et al. disclosed a highly enantioselective [3 + 2] antee the chemoselective formation of bicyclo[2.1.1]heptanes.
cycloaddition of N-arylcyclopropylamines with electron-rich or
electron-neutral olefins to access several kinds of biologically
important cyclopentylamine derivatives in high yields, ees and
drs (Scheme 7c).26d Very recently, Zhao and Jiang et al. have also
applied such cooperative photoredox and chiral H-bonding cata-
lysis in the asymmetric [3 + 2] photocycloaddition of cyclopropyl-
amines with electron-deficient olefins including 2-aryl acrylates/
ketones and cyclic ketone-derived terminal olefins, leading to the
synthesis of a range of pharmaceutically and biologically valuable
chiral cyclopentylamine derivatives (Scheme 7d).26e In 2022,
Fraile and Aleman et al. described an asymmetric synthesis of
cyclic β-amino carbonyl derivatives by a formal [3 + 2] photocy-
cloaddition between cyclopropylamine derivatives and co-
ordinated α,β-unsaturated acyl imidazoles enabled by Meggers’
chiral Rh(III)-photocatalyst (Scheme 7e).26f The in situ formation
of the substrate–catalyst complex accounts for both the photo- Scheme 8 Synthesis of 1-aminonorborneol via photocatalytic intra-
redox process and the enantiocontrol task. molecular [3 + 2] annulation of alkene-tethered aminocyclopropanes.

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 979
 View Article Online

Review Organic Chemistry Frontiers

Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

Scheme 9 Synthesis of 2-azanorbornanes via photocatalytic intra-

molecular [3 + 2] annulation of alkene-tethered
cyclopropylsulfonamides.

Scheme 10 The construction of aminobicyclo[3.1.1]heptanes via

photocatalytic intermolecular [3σ + 2σ] cycloaddition of cyclopropyl- Scheme 11 Photocatalytic intermolecular [3 + 3] annulations involving
amines with bicyclo[1.1.0]butanes. cyclopropylamines.

While extensive studies on the [3 + 2] photocycloaddition of ions and as a catalyst in organic polymerizations.31 Upon SET
cyclopropylamines with various 1,2-dipole partners to deliver oxidation by excited photocatalysts, TMEDA can also be easily
five-membered cycles have been well documented, other mani- converted into an amine radical cation. But unlike cyclopropyl-
folds of photocycloaddition to access six-membered cycles amines’ generation of distonic radical cations, the TMEDA
have been less achieved.30 In 2023, Yao and co-workers radical cation is susceptible to splitting itself into a separated
reported an Ir(III)-photocatalyst-induced cycloaddition of cyclo- α-aminoalkyl radical and an iminium ion (Scheme 12). Both
propylanilines with 2-alkenylarylisocyanides to access 3-amino- species are reactive intermediates and may undergo C–C or C–
tetrahydro-1H-carbazoles with high atom and step economy X (X = heteroatom) bond formation reactions. For instance, in
(Scheme 11a).30a In the transformation, 2-alkenylarylisocya- 2012, the Li and Wang group designed a concept for the frag-
nides serve as efficient radical acceptor platforms for the con- mentation of TMEDA 50 into iminium ion 52 and
comitant construction of both five- and six-membered rings. α-aminoalkyl radical 53 through a visible-light-driven C–C
In the same year, Li and co-workers for the first time explored
a radical-based [3 + 3] photocycloaddition of cyclopropyl-
amines with N,N′-cyclic azomethine imines to access dinitro-
gen-fused six-membered cyclic compounds with high cis-
diastereoselectivity by using Ir(dF(CF3)ppy)2(dtppy)PF6 as a
photocatalyst (Scheme 11b).30b Mechanistically, the transform-
ation undergoes a tandem process comprising the addition of
β-carbon radical iminium ions to azomethine imines and
sequential intramolecular 6-exo-trig cyclization. Very recently,
Zhou and Li reported a 4CzIPN-catalyzed [3 + 3] annulation of
cyclopropylamines and vinyldiazo compounds to deliver a
diverse array of cyclohexenes bearing adjacent amino and car-
bonyl groups with broad functional group tolerance
(Scheme 11c).30c In the process of cycloaddition, vinyldiazo
compounds act as active 1,3-dipole partners.
2.1.2 Amino radical cation species-induced cleavage of the
Cα–Cβ bond in tertiary amines. N,N,N′,N′-Tetramethylethylene-
diamine (TMEDA) is a representative bidentate tertiary amine,
which is widely used both as a ligand to coordinate with metal Scheme 12 Visible light-mediated C–C bond cleavage in TMEDA.

980 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

bond cleavage strategy.32 The resultant iminium ion and

α-aminoalkyl radical could engage in aza-Henry condensations
with nitroalkanes and radical photopolymerizations, respect-
ively (Scheme 12a & b).
In 2017, Opatz et al. reported a rare example of visible light-
induced C–C-σ-bond metathesis reaction (Scheme 13).33 The
transformation involves a complicated tandem process com-
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

prising the SET oxidation of tetrahydroisoquinoline derivatives

58 to yield amine radical cation intermediates 62, the gene-
ration of radical anions 65 from cyanopyridines 59 via the
light-induced SET processes, and the final C–C-σ-bond meta-
thesis between intermediates 62 and 65 to deliver
α-aminonitriles 60 and pyridine derivatives 61. In the reaction,
both the reactive intermediates arising from the amine radical Scheme 14 Photocatalytic synthesis of gem-difluoroalkenes from aryl
cation 62, namely benzyl radical 64 and iminium ion 63, par- sulfonium salts and α-(trifluoromethyl)styrenes under the catalysis of a
[Ru(bpy)3](PF6)2/TMEDA system.
ticipate in the C–C-σ-bond metathesis processes.
In 2022, Koenigs, Patureau and co-workers reported a
photocatalytic synthesis of gem-difluoroalkenes from aryl sulfo-
nium salts 67 and α-(trifluoromethyl)styrenes 68 enabled by a induced C–C bond cleavage may have great potential for the
[Ru(bpy)3](PF6)2/TMEDA catalytic system (Scheme 14).34 construction of complex molecules. In 2014, Stephenson et al.
Mechanistically, TMEDA plays an important role in the whole showcased an example of the synthesis of valuable natural pro-
reductive quenching catalytic cycle: first, TMEDA serves as an ducts including (–)-pseudotabersonine 78, (–)-pseudovinca-
electron donor to quench the excited [Ru(bpy)3](PF6)2, result- difformine 79, and (+)-coronaridine 80 from commercially
ing in the formation of a reductive Ru(I) species and an amine available catharanthine 74 through the visible-light photo-
radical cation. Second, the α-aminoalkyl radical arising from redox-promoted C–C bond fragmentation of catharanthine
the TMEDA radical cation is a key reductive agent for the con- radical cation 76 (Scheme 15).35 Compared with traditional
version of radical intermediate 71 into anion intermediate 72. thermal reactions for the C–C bond fragmentation of cathar-
Finally, the iminium ion arising from the TMEDA radical anthine, the photocatalysis approach has advantages of high
cation acts as a fluorine acceptor to assist the conversion of 72 yields, high chemoselectivity and mild reaction conditions.
into the target products 69 via the release of the fluorine In 2021, Wang’s group reported an interesting method for
anion. the diastereoselective construction of tetracyclic eight-mem-
Since tertiary amine motifs are frequently encountered in bered lactams through a dearomative Heck reaction and a
N-containing compounds including natural products, it is
reasonable to expect that the strategy of amine radical cation-

Scheme 13 Visible light-mediated C–C-σ-bond metathesis reaction Scheme 15 Photoredox catalysis enabling the synthesis of intermediate
between tetrahydroisoquinolines and cyanopyridines. 75 from (+)-catharanthine and further conversion to alkaloids 78–80.

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 981
 View Article Online

Review Organic Chemistry Frontiers

light-driven alkylative ring-opening of stable spiroindolines via

C–C bond cleavage (Scheme 16).36 Mechanistic experiments
showed that the spiroindolines can act as autocatalysts in the
transformations under light irradiation. Mechanistically, the
photoexcited spiroindoline 84 reduces perfluorobutyl iodide
via a SET process to deliver perfluorobutyl radical 86 and spir-
oindoline radical cation 85. Subsequently, the addition of
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

radical 86 to spiroindoline 81 may give radical intermediate

87. An SET oxidation of 87 by the previously generated spiroin-
doline radical cation 85 leads to the formation of cation inter-
mediate 88 along with the regeneration of spiroindoline 81. 88
undergoes C–C bond cleavage via β-scission to give iminium
ion 89, which is subsequently hydrolyzed by water to afford
the desired products 83 ( path a). Alternatively, although the
authors did not mention it in their article, we speculate that
the formation of a distonic radical iminium ion 91 (or 90) Scheme 17 Photocatalytic [3 + 2] cycloaddition of aziridines and dipo-
from spiroindoline radical cation 85 via a radical-induced larophiles involving C–C bond cleavage.
β-fragmentation is also possible. The direct radical coupling
between 91 and 86 may also deliver intermediate 89 ( path b).
Very recently, Dell’Amico and co-workers realized a novel
photocatalytic [3 + 2] dipolar cycloaddition reaction of aziri-
dines with various types of dipolarophiles to access pyrroli-
dines and dihydropyrroles with high chemo-, regio- and
diastereoselectivities (Scheme 17).37 In this transformation,
aziridine radical cation-induced Cα–Cβ bond cleavage and the
subsequential photoreduction of the resultant distonic radical
cation 98 play essential roles in the formation of the key azo-
methine ylide 99.
2.1.3 Amino radical cation species-induced cleavage of the
Cα–Cβ bond in N-containing heterocycles. In 2022, the Protti
and Fagnoni group reported a convenient method for the gene-
ration of alkyl radicals from 2-substituted oxazolidines via C–C
bond cleavage under mild photocatalytic conditions
(Scheme 18).38 A series of alkyl radicals including tertiary,
α-oxy and α-amido radicals can be readily generated upon SET
oxidation of 2-substituted oxazolidines to the amine radical

Scheme 18 Visible light-mediated C–C bond cleavage in 2-substituted

oxazolidines and subsequent application in alkylation reactions.

cations by the excited [Acr-Mes]+[BF4]− photocatalyst. The

resulting alkyl radicals can be easily trapped by electron-poor
olefins or vinyl (hetero)aromatics.
In the same year, Martin and co-workers described an
elegant protocol for the generation of open-shell alkyl radical
intermediates from dihydroquinazolinones through C–C bond
cleavage initiated from the β-fragmentation of the amine
radical cations enabled by 4CzIPN under photoredox catalysis
conditions (Scheme 19).39 The resulting alkyl radicals can
engage in cross-coupling reactions with aryl or alkyl bromides
to efficiently forge (sp2)C–(sp3)C or (sp3)C–(sp3)C bonds
Scheme 16 Photocatalytically diastereoselective synthesis of tetra- enabled by a photoredox/nickel dual catalysis under mild and
cyclic eight-membered lactams involving C–C bond cleavage. environmentally-friendly reaction conditions.

982 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

respectively. After the publication of these reviews, the

research studies on this domain were even more frequently
documented in the literature.43c,44 Regarding the Hantzsch
ester-involved photocatalytic alkylation reactions, the pro-
duction of a stable aromatic pyridine ring acts as the driving
force for facilitating the cleavage of the Cγ–Cδ bonds in
Hantzsch ester radical cations in the presence of photocata-
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

lysts (Scheme 20b-I).21 It should be noted that in some reac-

tions, Hantzsch esters can also directly absorb the energy of
Scheme 19 Photocatalytic synthesis of (sp2)C–(sp3)C or (sp3)C–(sp3)C
light and convert themselves into the excited state. The excited
bonds enabled by photoredox/nickel dual catalysis using dihydroquina- Hantzsch esters then undergo the homolytic cleavage of the
zolinones as alkyl radical precursors. Cγ–Cδ bonds and can also release alkyl free radicals even in
the absence of a photocatalyst (Scheme 20b-II).45
Despite much advance in the utilization of alkyl-substituted
2.2. Amino radical cation species-induced cleavage of Cγ–Cδ Hantzsch esters in photocatalytic reactions, the asymmetric
bonds photocatalytic reactions involving Hantzsch esters as alkyl
As well-designed alkyl radical precursors, alkyl-substituted radical precursors have been underdeveloped.41c,44a–d In 2022,
Hantzsch esters are easy to undergo N-γ-fission under photo- the Xiao group achieved a dynamic kinetic asymmetric trans-
catalytic conditions to release alkyl radicals and stable pyridine formation of racemic heterobiaryls to the corresponding axial
derivatives.21 Since Tang’s group first employed alkyl-substi- chirality frameworks through an asymmetric radical trapping/
tuted Hantzsch esters in the formation of C–C bonds that are cross-coupling reaction enabled by an asymmetric Ir/Ni metal-
difficult to achieve by other conventional methods laphotoredox dual catalysis system under visible light con-
(Scheme 20a),40 these amine derivatives have been widely ditions (Scheme 21a).44a In the transformation, alkyl-substi-
applied in photocatalytic free-radical functionalization reac- tuted Hantzsch esters were used as the alkyl radical precur-
tions. To date, a variety of C–C or C–X (X = heteroatom) for- sors. In 2023, Jiang and co-workers reported a novel and
mation reactions have been explored using alkyl-substituted efficient method for the asymmetric synthesis of azarene-func-
Hantzsch esters as alkyl radical precursors under photo- tionalized tertiary amines and α-amino acid derivatives via the
catalytic reaction conditions, including free radical substi- enantioselective reductive coupling of azarene-substituted E/
tution reactions,41 free radical addition reactions,42 photo- Z-ketimine mixtures with 1,4-hydropyridines enabled by the
redox/nickel dual catalyzed cross-coupling reactions,43 etc. cooperative photoredox and chiral Brϕnsted acid catalysis
(Scheme 20b). In 2017 and 2019, Cheng21a and Xiao21b well (Scheme 21b).44b Very recently, Lu’s group realized an enantio-
summarized the progress in the utilization of Hantzsch esters convergent cross-coupling reaction of 1,4-dihydropyridine
as radical alkylating reagents in photocatalytic reactions,

Scheme 20 Pioneering and selected photocatalytic C–C bond for-

mation reactions involving N-γ-fission of Hantzsch esters and two Scheme 21 Photocatalytic asymmetric transformations involving alkyl-
related mechanisms for the N-γ-fission. substituted Hantzsch esters as alkyl radical precursors.

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 983
 View Article Online

Review Organic Chemistry Frontiers

derivatives with aryl/alkenyl halides via a photoredox/nickel vide infra) or undergo radical-induced Cβ–Cγ bond cleavage to
dual catalysis (Scheme 21c).44c The reaction has advantages of generate an alkyl radical and an enamine species (Scheme 2c,
good efficiency, high enantioselectivity and mild reaction con- vide supra). While the former scenario of β-fragmentation
ditions. This strategy can not only be used for the synthesis leading to the Cα–N bond scission has been reported for many
and modifications of drug molecules and natural products, years,47,60–62 the latter scenario of β-fragmentation resulting in
but also for the one-pot construction of molecules with mul- the Cβ–Cγ bond cleavage has not been discovered until
tiple stereocenters. In the same year, the You group realized a recently.48 In 2024, almost at the same time, Meng’s group48a
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

dual photoredox/Rh-catalyzed asymmetric allylic substitution and Yu’s group48b for the first time independently discovered
reaction between 4-alkyl-1,4-dihydropyridines and allyl acetates such a reactivity associated with an in situ generated
under visible light conditions, resulting in the formation of α-aminoalkyl radical intermediate which is the key factor for
alkylation products in moderate to good yields with good to the tertiary amine-assisted deconstructive carboxylation of
excellent enantioselectivity (Scheme 21d).44d alkenes with carbon dioxide under visible light photoredox
Similarly, carbonyl-substituted Hantzsch esters,46 as ana- conditions (Scheme 23). In this transformation, the tertiary
logues of alkyl-substituted Hantzsch esters, have been explored amine N,N-dicyclohexylmethylamine is first oxidized into an
and serve as promising carbonyl radical precursors upon their α-aminoalkyl radical by the excited photocatalyst 4DPAIPN
Cγ–Cδ bond cleavage under photoredox catalytic conditions (1,3-dicyano-2,4,5,6-tetrakis(diphenylamino)-benzene) (or
(Scheme 22). Thus, a variety of carbonyl-functionalization- 3DPA2FBN (2,4,6-tris(diphenylamino)-3,5-difluorobenzonitrile)
related photocatalytic reactions have been achieved by harnes- using Yu’s procedure) via an SET oxidation process followed by
sing carbonyl-substituted Hantzsch esters as carbonyl radical the release of a proton. The addition of the α-aminoalkyl
equivalents in recent years. radical 162 across alkenes generates radical intermediate 163.
An SET reduction of 163 by the reductive species PS•− followed
2.3. α-Aminoalkyl radical species-induced cleavage of Cβ–Cγ by carbonylation with CO2 and protonation affords γ-amino
bonds acid 165. Upon SET oxidation, tertiary amine 165 may generate
Upon SET oxidation by excited photocatalysts, tertiary amines another type of α-aminoalkyl radical 166. The radical-induced
are susceptible to conversion into α-aminoalkyl radicals via β-scission of the Cβ–Cγ bond in 166 results in the formation of
elimination of a proton from amine radical cations.19 The radical intermediate 168 and enamine species 167. The SET
resultant α-aminoalkyl radicals can either undergo radical- reduction of 168 by the reductive species PS•− followed by pro-
induced Cα–N bond cleavage to form an alkyl radical and an tonation gives the final carboxylic acid 160. It is worth noting
imine species (Scheme 3d, vide supra; also see section 3.3, that the present destructive carboxylation of carbon–carbon
double bonds provides a unique approach for accessing car-
boxylic acids, which has advantages of easily available starting
materials, a broad substrate scope, convenient application in

Scheme 22 Photocatalytic transformations involving carbonyl-substi- Scheme 23 Photocatalytic deconstructive carboxylation of activated
tuted Hantzsch esters as carbonyl radical precursors. olefins involving α-amino radical-induced CvC bond cleavage.

984 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

the late-stage carboxylation of bioactive molecule derivatives, α-aminoalkyl radical metathesis process is successfully
and mild reaction conditions. achieved. Notably, the produced enamine species could be suc-
In the same year, by adopting a similar “α-aminoalkyl cessfully detected and confirmed by high-resolution mass
radical-induced site-selective cleavage of the Cβ–Cγ bond” strat- spectrometry (HRMS), supporting the above-mentioned olefin-
egy, the Liu group achieved an interesting demethylenative en- radical exchange process. As for subsequent transformations,
yne radical cyclization of 1,7-enynes to chemoselectively afford 179 (or 180) is reduced by the reductive Cu(0) species to give
3,4-dihydroquinolin-2-ones or quinolin-2-ones through a con- anion intermediate 181 (or 182) and regenerate the Cu(I)-
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

ceptually novel olefin-radical metathesis-type reaction enabled photocatalyst. Finally, either the protonation and the sub-
by P/N-heteroleptic Cu(I)-photocatalysts under photoredox cat- sequent 1,3-allylic isomerization of 181 or the direct protona-
alysis conditions (Scheme 24).48c To realize the olefin-radical tion of 182 affords quinolin-2-one-type product 171a.
metathesis process and the demethylenative en-yne cycliza- Interestingly, under the catalysis of Cu1 having a more strongly
tion, they proposed a protocol termed the “radical-lending/ reductive capability than Cu2, 171a can be further converted to
methylene-returning” strategy by harnessing an α-aminoalkyl 172a through a PCET-involved reductive pathway. Later, the
radical as a suitable radical exchange partner with olefin. The same group further disclosed that an in situ generated
detailed mechanism of this transformation is illustrated in α-aminoalkyl radical 188 from propionaldehyde 185 and di-
Scheme 24. First, an α-aminoalkyl radical 174 can be in situ propylamine 186 in the presence of Hantzsch ester 187 and Cu
generated from Et3N upon SET oxidation by the excited Cu(I)- (I)-photocatalyst Cu1 can also efficiently act as a traceless
photocatalyst. The addition of 174 across the terminal olefin initiator for the demethylenative cyclization of 1,7-enynes to
unit of 1,7-enyne 170a is followed by intramolecular radical access quinoline-2-ones under mild conditions.48d It is worth
cyclization to deliver radical intermediate 176 (the radical noting that the use of different α-aminoalkyl radicals in these
lending process). Then 176 undergoes a 1,5-HAT process to two protocols leads to a big difference in the substrate scope.
generate a new α-aminoalkyl radical 177. After that, 177 under- Thus, in the case of α-aminoalkyl radical 174 as the reaction
goes a site-selective cleavage of the original (sp2)C–(sp2)C bond initiator, the 1,7-enyne scope will be limited to those having
of the terminal olefin moiety to generate radical 179 (or 180) no substituents at the α-position to the carbonyl group;48c
and release a molecule of enamine 178 (the methylene return- whereas in the case of α-aminoalkyl radical 188 as the reaction
ing process). At this stage, as a net result, the formal olefin- initiator, either 2-substituted- or 2-substituent-free-1,7-enynes
are viable for the demethylenative en-yne cyclizations.48d
Shortly after the Liu group published the above findings,
Singh’s group48e and Li’s group48f reported similar research
studies on the photocatalytic, α-aminoalkyl radical-triggered,
demethylenative en-yne cyclizations (Scheme 25). In Singh’s
research work, Ru(bpy)3Cl2·6H2O was employed as the photo-

Scheme 24 Cu(I)-photosensitizer-controlled chemoselective olefin- Scheme 25 Photocatalytic deconstructive cyclizations of 1,7-enynes

α-aminoalkyl radical metathesis/demethylenative cyclization of 1,7- and/or o-cyano acrylamides using α-aminoalkyl radicals as traceless
enynes. initiators.

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 985
 View Article Online

Review Organic Chemistry Frontiers

catalyst and the α-aminoalkyl radical 188 derived from N,N-di- than C–X (X = Cl, Br, I etc.) bonds.3 In the past few decades,
methylaniline 187 was used as the initiator for the ring-closing despite the great progress that has been made in the tran-
transformations. In addition, they further expanded their pro- sition-metal-catalyzed cleavage of the C–N single bond under
tocol for the demethylenative cyclization of o-cyano acryl- thermal conditions,5 yet there remain huge challenges in this
amides to access carbostyril derivatives in good yields domain and there is a need to search for novel and highly
(Scheme 25a). In Li’s research findings, they achieved diver- efficient strategies for pursuing these tasks. With the flourish-
gent demethylenative ring-closing of 1,7-enynes under photo- ing of visible light-driven organic photochemical synthesis in
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

redox catalysis conditions depending on different recent years,14 the utilization of visible light-induced photo-
α-aminoalkyl radical promoters and different structural var- catalytic strategies for the cleavage of C–N bonds has received
iants of 1,7-enynes (Scheme 25b). Thus, when the increasing attention because such photocatalytic transform-
α-aminoalkyl radical derived from dicyclohexylmethylamine ations have special advantages of mild reaction conditions,
(MeCy2) is used as the promoter under the catalysis of an Ir unique selectivity and sustainable processes. Herein, we intro-
(III)-photocatalyst, type-I and type-II 1,7-enynes afford nonspiro- duce the recent advances in the cleavage of unactivated C–N
cyclic 192 and spirotricyclic quinolin-2-one derivatives 193 as bonds associated with amines and their derivatives via visible-
the major products, respectively. Besides, when the light-driven photocatalytic pathways.
α-aminoalkyl radical derived from TMEDA is used, type-III 1,7-
enynes deliver spirotetracyclic quinoline-2-one derivatives 194 3.1. Cleavage of C–N bonds in tertiary amines via iminium salts
as the predominant products. Tertiary amines represent a class of important and useful feed-
stocks as well as synthetic intermediates in organic synthesis.
2.4 α-Aminoalkyl radical species-induced cleavage of Cα–Cβ Upon C–N bond cleavage, they can be fragmented into two
bonds in the presence of O2 parts, namely the carbon-linked fragment and the nitrogen-
In 2017, the Wang group reported a visible-light-induced oxi- linked fragment, both of which may serve as useful synthetic
dative formylation of N-alkyl-N-(prop-2-yn-1-yl)anilines with O2 building blocks in organic synthesis. In the past few decades,
involving C–C bond cleavage (Scheme 26a).49 Mechanistic methods involving the transition-metal-catalyzed oxidative
studies disclosed that the in situ generated peroxide intermedi- cleavage of C–N bonds in tertiary amines via iminium ions
ate from α-aminoalkyl radical species and O2 plays a key role have received much attention in organic synthesis due to the
in achieving the Cα–Cβ bond cleavage. In the same year, they convenient generation of secondary amines and carbonyl syn-
also realized oxidative formylation of N-methyl substituted ani- thons via the hydrolysis of iminium ions.9 Nevertheless, under
lines with O2 to access formamides under the irradiation of thermal reaction conditions, such procedures generally
visible light (Scheme 26b). suffered from harsh reaction conditions. With the rapid devel-
opment of visible-light-mediated photocatalysis, photoinduced
two electron oxidation of tertiary amines into iminium ions
has evolved into a powerful and sustainable strategy for the
3. Photocatalytic cleavage of C–N fragmentation of tertiary amines into useful amine and/or car-
bonds bonyl synthons.
In 2014, Li and co-workers reported a Rose bengal-pro-
The C–N bond is ubiquitous in organic molecules. A large
moted indole C-3 formylation reaction under aerobic con-
number of C–N bond-containing compounds show great
ditions using TMEDA as the one-carbon source through C–N
potential for serving as nitrogen and/or carbon sources in
bond cleavage (Scheme 27a).50 In the tandem processes for the
organic synthesis upon cleavage of C–N bonds. Nevertheless,
formation of 3-indolyl formaldehydes, the photoredox-induced
the cleavage of C–N bonds5 is not an easy task because their
successive generation of iminium ion species 201 and 203
dissociation energies are very high and they are less polarized
plays a key role in the whole transformation. In 2015, Cho’s
group developed a photocatalytic method for the oxidative C–N
bond cleavage in amines to access carbonyl compounds along
with NH3 or amines as byproducts under the catalysis of
Ru(byp)3Cl2 (Scheme 27b).51 However, rather than an iminium
ion-involved mechanism, in their proposed one, the nucleo-
philic addition of water to the photoredox-generated imine
species followed by an elimination of the amine byproduct
accounts for the formation of carbonyl compounds. Notably,
this protocol also permits the removal of a p-methoxybenzyl
(PMB) group from N-PMB protected amides 207 via the photo-
catalytic C–N bond cleavage.
In 2022, Xie’s group achieved a visible-light-mediated ami-
Scheme 26 Visible-light-induced oxidative formylation of N-alkyl-N- dation reaction between carboxylic acids and tertiary amines
( prop-2-yn-1-yl)anilines and N-methyl substituted anilines. via C–N bond cleavage in the presence of pentafluoropyridine

986 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

through the hydrolysis of self-derived iminium ions 217 under

photoredox catalysis conditions. The nucleophilic addition of
secondary amines 218 to acyl radicals 215 followed by a SET
oxidation process delivers the target products tertiary amides
212. The present protocol exhibits a broad substrate scope of
carboxylic acids and good functional group tolerance.
In 2023, Rovis and co-workers reported a photoinduced
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

nickel-catalyzed N-demethylation of tertiary amines with high

chemoselectivity by harnessing C(sp2)–bromides as HAT
reagents (Scheme 29).53 Mechanistic studies disclosed that
after the Ni(0) oxidative addition to the C(sp2)–Br bond, a
photoinduced homolysis of the C(sp2)–Ni bond (224) occurs to
produce aryl radical intermediate 225. A hydrogen-atom trans-
fer (HAT) process between 225 and tertiary amines 219 pro-
ceeds to deliver α-aminomethyl radical 226. 226 can be inter-
cepted by Ni(I)-OPiv to obtain an Ni(II) intermediate 227,
which is in equilibrium with the iminium ion 228. Finally, the
cleavage of the C–N bond occurs upon the hydrolysis of the
iminium ion 228, leading to the formation of N-demethylation
Scheme 27 Photocatalytic deconstructive cyclizations of 1,7-enynes
product 221 and formaldehyde. The advantages of this photo-
and/or o-cyano acrylamides using α-aminoalkyl radicals as traceless
initiators. induced nickel-catalyzed N-demethylation protocol lie in
chemoselective demethylation, excellent functional group
compatibility, and mild reaction conditions.
under the catalysis of [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 Apart from the precursors of secondary amines, tertiary
(Scheme 28).52 In this transformation, pentafluoropyridine amines can also serve as the precursors of carbonyl synthons
acts as an activating agent for the generation of acyl radical upon C–N bond cleavage via iminium ions. In 2024, Senadi
intermediate 215 from carboxylic acids 210, and tertiary and Arumugam reported a three-component approach for the
amines 211 serve as the source of secondary amines 218 construction of 2,4-difunctionalized quinazolines from o-acyla-
nilines, trialkylamines and ammonium chloride catalyzed by
eosin Y under visible-light photoredox catalysis conditions,

Scheme 28 Visible-light-mediated photocatalytic amidation from car- Scheme 29 Selective N-demethylation of trialkylamines using C(sp2)–
boxylic acids and tertiary amines involving C–N bond cleavage. bromides as HAT reagents enabled by photoredox/nickel dual catalysis.

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 987
 View Article Online

Review Organic Chemistry Frontiers

wherein tertiary amines serve as the source of alkyl aldehydes

for the condensation with o-acylanilines (Scheme 30).54
Notably, the practicability of this method has been further
used in the synthesis of 2-hydroxymethyl quinazolines by
using easily available triethanolamine as a C2-OH source.

3.2. Cleavage of C–N bonds via amine radical cation species

Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

In 2021, Sekine and Kuninobu reported a photoinduced dea-

minative borylation of inactive aniline derivatives with bis
( pinacolato)diboron (B2Pin2) in the presence of CO2 under the
catalysis of pyrene (Scheme 31a).55 According to the proposed
mechanism, the reaction proceeds through a tandem process
including the formation of a complex of the arylamino radical
cation with B2Pin2 (243), the concerted C–N/B–B bond meta-
thesis of 243 leading to the formation of borylated products
241 and aminoboryl radical cations 244, and the final for-
mation of aminoborane byproduct 242 via an SET reduction
event. Later, Zhang’s group reported a different strategy to acti-
vate the C–N bond of non-reactive aniline derivatives and
achieved a photoinduced aerobic borylation of various tertiary
and secondary anilines (Scheme 31b).56 Mechanistic studies
showed that the active singlet oxygen 1O2 reacts rapidly with
aniline 245 to obtain an aniline cation radical 248 and O2•−. Scheme 31 Photocatalytic C–N/B–B bond metathesis reactions for the
Then the cation radical 248 reacts with B2pin2 via C–N/B–B construction of aryl boronate esters: Sekine and Kuninobu’s work vs.
Zhang’s work.
bond metathesis to obtain aryl boronate ester product 246
along with aminoboronate ester cation radical 249. Finally, a
single electron transfer from O2•− to 249 delivers aminoboro-
nate ester 247.
In 2023, Zou et al. reported a photochemical reductive deami-
nation of α-amino aryl alkyl ketones to access the corresponding
ketone products (Scheme 32).57 Preliminary mechanistic studies
disclosed that the reaction possibly proceeds through a key
amino radical cation-induced C–N bond cleavage pathway,
leading to the formation of ketone products and hydroxyamine
byproducts (path a). Alternatively, a pathway involving an
α-aminoalkyl radical intermediate-induced β-fragmentation to lib-
erate a molecule of imine is also possible (path b).

Scheme 32 Photoinduced reductive deamination of α-amino aryl alkyl

ketones.

3.3. Cleavage of C–N bonds via amine cation species

In 2021, Yang et al. developed a facile and practical protocol
for the direct methylation of N-heteroarenes by using TMEDA
as a methyl source through a photoredox-catalyzed deamina-
tion process (Scheme 33a).58 The mechanism studies revealed
that an amine cation species-induced amine-elimination event
is the key step to enable TMEDA as a C1 synthon for the C–H
bond methylation. In 2024, Fan et al. reported a method for
Scheme 30 Photocatalytic synthesis of quinazolines from tertiary the photocatalytic synthesis of 2,3-diamines from anilines and
amines via C–N bond cleavage. DIPEA in the presence of aromatic aldehydes through C–N

988 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

Scheme 34 Tertiary amines acting as carbon sources for the inter-

molecular coupling with 1,3-diketones enabled by Eosin Y under photo-
redox catalysis conditions.

release a proton.19 The generated α-aminoalkyl radicals serve

as useful reactive intermediates in a broad range of photo-
catalytic reactions, typically acting as nucleophilic radical
species in radical addition, substitution, and cross-coupling
reactions.19 In most cases, α-aminoalkyl radicals do not
undergo a C–N bond cleavage event. Yet in recent several
years, photocatalytic transformations that involve a C–N bond
Scheme 33 Visible light-induced C–N bond cleavage from amine cleavage event associated with reactive α-aminoalkyl radical
cation species: Yang’s work and Fan’s work. intermediates have been gradually achieved. In 2020, the Liu
group reported a P/N heteroleptic Cu(I)-photosensitizer-cata-
lyzed deoxygenative radical alkylation of aryl alkynes with alkyl
bond cleavage and C–C bond formation (Scheme 33b).59 They aldehydes to access allylarenes by using dipropylamine as a
subtly employed DIPEA as a C2 synthon to participate in the traceless linker agent (Scheme 35).61 In the tandem radical
reassembly with anilines to access 2,3-diamines. process, an α-aminoalkyl radical 290 is first in situ generated
Mechanistically, the photo-oxidation of DIPEA in conjunction from alkyl aldehyde and dipropylamine in the presence of a
with the aromatic aldehyde-assisted PCET ( proton-coupled
electron transfer) process generates iminium ion species 272.
The nucleophilic addition of anilines 265 to iminium 272
affords amine cation tautomers 273 and 274, which may
undergo a C–N bond cleavage event via the elimination of a
molecule of diisopropylamine, leading to the formation of
another type of iminium ion 275. Finally, photoreduction of
275 followed by the dimerization of the resultant α-aminoalkyl
radical 276 gives the final products 267. It should be noted
that under the photoredox catalysis conditions, aromatic alde-
hydes can be converted into 1,2-diol products 271.
In the same year, Gnaprakasam et al. successfully utilized
tertiary amines as alkyl synthons via C–N bond cleavage to syn-
thesize biologically active tetraketones under visible-light
photocatalytic conditions (Scheme 34).60 Similar to Fan’s pro-
tocol,59 the key to the implementation of this strategy lies in
the formation of iminium ion 280 and the deamination
process of intermediate 281.

3.4. Cleavage of C–N bonds via α- or β-aminoalkyl radical

species
Upon the single-electron oxidation by photocatalysts, tertiary
Scheme 35 Alkyl aldehydes acting as deoxygenative alkyl radical
amines are easily converted into amine radical cations which equivalents for the coupling with aryl alkynes using secondary amines as
subsequently undergo deprotonation of the C–H bond adja- traceless linker agents enabled by P/N–Cu(I)-photosensitizers under
cent to the N-atom to generate α-aminoalkyl radicals and visible-light photoredox catalysis conditions.

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 989
 View Article Online

Review Organic Chemistry Frontiers

P/N-heteroleptic Cu(I)-photocatalyst and Hantzsch ester. Then

the regioselective addition of α-aminoalkyl radical 290 across
aryl alkyne 284 yields radical intermediate 291. 291 undergoes
1,5-HAT to generate another α-aminoalkyl radical-type inter-
mediate 292, which subsequently undergoes a radical-induced
β-fragmentation of the N–Cα bond to deliver allylic radical 294
and imine 293. Finally, 1,3-allylic isomerization of 294 to 295
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

followed by a HAT process from dipropylamine radical cation

297 and/or water delivers the final products 288. As a net
result, this protocol provides a unique way to utilize commer-
cially available alkyl aldehydes as deoxygenative-type alkyl
radical equivalents without the occurrence of decarbonylation.
In the whole transformation, dipropylamine serves as a trace-
less linker agent for the cross-coupling of aryl alkynes and
alkyl aldehydes.
On the basis of the above mechanistic profile and the fact
that α-aminoalkyl radicals can be directly generated from ter-
tiary amines through SET oxidation processes, Liu’s group sub-
sequently realized an efficient method for the synthesis of ally-
larenes directly from tertiary amines and aryl alkynes enabled
by a similar P/N-heteroleptic Cu(I)-photosensitizer
(Scheme 36).62 In these transformations, tertiary amines play
dual roles as quenching agents for the excited Cu(I)-photo-
catalyst and alkylating equivalents for the cross-coupling with
alkynes. This is the first endeavour to employ tertiary amines
as deaminative alkyl radical equivalents in photocatalytic
reactions.
After successfully using non-chiral alkyl aldehydes as deoxy-
genative alkyl radical equivalents in the alkylation with aryl Scheme 37 α-Chiral alkyl aldehydes acting as deoxygenative chiral
alkynes,61 in 2023, the Liu group further expanded their proto- alkyl radical equivalents for the alkylation/cyclization of 2-biphenylisoni-
col to harness α-chiral alkyl aldehydes as deoxygenative chiral triles enabled by 4CzIPN using secondary amines as traceless linker
agents.
alkyl radical equivalents as showcased in a 4CzIPN-catalyzed
deoxygenative alkylation/cyclization of 2-biphenylisonitriles to
access chiral 6-alkyl-substituted phenanthridines by using sec-
ondary amines as traceless linker agents (Scheme 37).63 molecular homolytic aromatic substitution (HAS) to yield
Notably, in most cases, the ee values of the employed chiral radical species 304. An SET oxidation of 304 followed by the
α-amino aldehydes remain at high levels of retention. release of a proton delivers phenanthridinyl-tethered tertiary
Mechanistically, the in situ generated α-amine radical 302 amine 305. Upon SET oxidation and release of a proton, 305
undergoes radical addition across 2-biphenylisonitriles 296 to may be converted into an α-amino radical 307, which further
obtain imine radical intermediate 303 which undergoes intra- undergoes β-fragmentation of the N–Cα bond to deliver radical
intermediate 309 along with imine species 308. Finally, 309
abstracts a hydride from HE•+ to afford the target products
300a.
In the same year, Kang and co-workers also realized an
α-aminoalkyl radical-involved deaminative alkylation/cycliza-
tion of 2-biphenylisonitriles to access 6-alkyl-substituted phe-
nanthridines under photoredox catalysis conditions
(Scheme 38).64 In Kang’s protocol, tertiary amines were
employed as the sources of α-aminoalkyl radicals and a super
organophotoreductant CBZ6 was used as the photocatalyst.
Based on preliminary mechanistic experiments, the authors
proposed a possible mechanism for the deaminative alkyl-
ation/cyclization reaction. According to their proposed mecha-
Scheme 36 Tertiary amines acting as deaminative alkyl radical equiva-
nism, the key step for the C–N bond cleavage does not involve
lents for the alkylation of aryl alkynes enabled by P/N-heteroleptic Cu(I)- an event comprising an α-aminoalkyl radical intermediate and
photosensitizers. the liberation of imine, as reported in Liu’s protocol,63 but

990 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

Scheme 40 Photocatalytic C–N bond cleavage enabling 1,4-aryl

migration in heteroarylamines.

3.5. Cleavage of C–N bonds via miscellaneous other ways

Scheme 38 Photocatalytic alkylation/cyclization of 2-biphenylisoni-
triles by tertiary amines via C–N bond cleavage enabled by the super 3.5.1 Cleavage of C–N bonds in redox-active imines.
organophotoreductant CBZ6. Primary amines play an important role in organic synthesis
due to their easy availability and versatile reactivity. Among
various strategies for using primary amines as valuable syn-
involves an event comprising a β-aminoalkyl radical intermedi- thons, the conversion of primary amines into Katritzky salts10
ate (or an α-amino anion intermediate) and the release of a is an elegant protocol that enables them to act as useful alkyl
secondary amine. radical equivalents via C–N bond cleavage under suitable
Very recently, the Ota and Yamaguchi group achieved a site- reductive conditions, certainly including visible-light photo-
selective C–N bond cleavage in unstrained pyrrolidines redox catalysis conditions. Despite much advance in the appli-
enabled by a combination of Lewis acid and photoredox cataly- cation of Katritzky salts in organic synthesis, their synthesis is
sis (Scheme 39).65 In this photocatalytic transformation, limited to α-1° and α-2° amines, whereas α-3° primary amines
photocatalytic SET reduction of the Lewis acid-activated amide are not viable for their conversion into the corresponding
produces an α-amino radical intermediate which undergoes Katritzky salts due to their steric hindrance. On the other
the key Cα–N bond cleavage. hand, the harnessing of Katritzky salts as alkyl radical sources
In 2018, the Stephenson group reported a visible-light- generally requires a reductive event. To circumvent these pro-
mediated 1,4-aryl migration reaction of haloalkylamides to blems, in 2020, Rovis and co-workers proposed an elegant syn-
access aminoalkylated heteroarenes involving a homolytic C–N thetic platform that can enable α-3° primary amines to act as
bond cleavage event (Scheme 40).66 According to their pro- alkyl radical equivalents through the photochemical oxidation
posed mechanism, the photocatalytically generated spiro- of redox-active imines (RAIs) arising from the condensation of
β-amino radical intermediate 325 undergoes the key C–N bond α-3° primary amines with trimethoxybenzaldehyde
cleavage process to accomplish 1,4-aryl migration. (Scheme 41).67 Mechanistically, the single-electron oxidation
of the electron-rich phenyl ring in RAIs, followed by a deproto-
nation of imidoyl-H and a spin-centered-shift (SCS) event,
leads to the formation of a key imidoyl radical species 333.
The subsequent β-scission of imidoyl radical 333 leads to the
C–N bond cleavage and the release of a nucleophilic alkyl
radical 334, which can further be trapped by electron-deficient
olefins. Rovis’ protocol provides an ideal solution for the
employment of α-3° primary amines as alkyl radical equiva-
lents, something that is not feasible with Katritzky salts, which
will arouse great interest in the field of organic synthesis.
In 2021, Rovis and coworkers further expanded their proto-
col for the achievement of a dual nickel/photoredox-catalyzed
deaminative cross-coupling of sterically encumbered primary
amines with aryl halides to forge quaternary center-containing
(sp3)C–(sp2)C bonds through the conversion of primary
amines into RAIs (Scheme 42).68 The reaction exhibits broad
Scheme 39 Site-selective C–N bond cleavage in unstrained pyrroli-
substrate compatibility for both amines and aryl halides and
dines enabled by the combination of Lewis acid and photoredox can also be applicable in the construction of medicinally rele-
catalysis. vant scaffolds, e.g., for the synthesis of ALK2 inhibitors.

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 991
 View Article Online

Review Organic Chemistry Frontiers

aryl halides with Rovis’ redox-active imines enabled by a

photoredox/nickel dual catalysis.70 It is worth noting that in
their protocol, an organophotocatalyst 4CzIPN exhibits better
catalytic efficiency than the Ir(III)-based photocatalysts used in
Rovis’ protocols.67–69 In the same year, Liu’s group achieved a
photocatalytic deaminative alkylation of DNA-tagged alkenes
with tertiary amine-derived imines as radical precursors;71 the
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

Liang group reported a visible-light-induced deaminative alkyl-

ation of trifluoromethyl-substituted alkenes to access gem-
difluoroalkenes by using Rovis’ alkylation protocol.72 In 2023,
Chen and co-workers described a similar photocatalytic trans-
formation to Liang’s work for the synthesis of gem-difluoroalk-
enes, although by using 4CzIPN as a photocatalyst.73
3.5.2 Cleavage of C–N bonds in isonitriles. As mentioned
in 3.5.1, the conversion of α-1° and α-2° primary amines into
Katritzky salts can enable them to act as deaminative alkyl
Scheme 41 RAIs as deaminative 3°-alkyl radical equivalents enabled by radical equivalents,10 whereas the transformation of α-3°
visible light photoredox catalysis. primary amines into RAIs can allow them to serve as deamina-
tive tertiary alkyl radical equivalents.67–73 Despite much pro-
gress being made in both strategies, a general strategy that can
permit all types of primary amines to serve as deaminative
alkyl radical precursors is still rare. In 2024, Tortosa and co-
workers reported a photochemical hydrodeamination reaction
of isonitriles wherein various types of amine (α-1°, α-2° and
α-3°)-derived isonitriles have been successfully used as alkyl
radical precursors through C–N bond cleavage under visible-
light irradiation (Scheme 43).74 The visible-light-mediated
reaction can proceed with or without the addition of a photo-
catalyst, but the addition of an organophotocatalyst 4CzIPN
causes significant rate acceleration for the reaction. On the

Scheme 42 Deaminative cross-coupling of RAIs with aryl halides

enabled by a nickel/photoredox dual catalysis.

Very recently, the same group described a method for the

efficient generation of tertiary carbanions from primary
amines via a photoredox-catalyzed deaminative radical-polar
crossover strategy.69 The resultant tertiary carbanions are ver-
satile nucleophiles that can be trapped by a series of electro-
philes including aldehydes, ketones, imines, Michael accep-
tors, and H2O/D2O. As a net result, the redox-active imines
(RAIs) derived from primary amines and trimethoxybenzalde-
hyde can be regarded as alkyl carbanion equivalents under the
reported photoredox catalysis conditions. Scheme 43 Isonitriles as deaminative alkyl radical equivalents for the
Inspired by Rovis’ research studies, in 2022, Huang and hydro(deutero)deamination reactions under visible light photocatalytic
Rueping achieved a regiodivergent cross-coupling alkylation of reaction conditions.

992 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

basis of preliminary mechanistic studies, the authors proposed

a possible mechanism for the hydrodeamination reaction of
isonitriles. The oxidative quenching of the excited 4CzIPN
(PC*) by isonitriles 338 results in the generation of radical
anion species 341 and PC•+. The occurrence of C–N bond clea-
vage in 341 leads to the generation of alkyl radical species 342
along with the release of CN−. The alkyl radical 342 may
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

abstract a proton from silane 339 to deliver the target hydro-

deamination products 340 and silyl radical 343. The SET oxi-
dation of 343 by PC•+ delivers silyl cationic species 344 and
regenerates the ground state 4CzIPN (PC). Finally, 344 is
trapped by CN− to give (TMS)3SiCN 345. Scheme 45 Deaminative C(sp3)–C(sp3) cross-coupling of primary
3.5.3 Cleavage of C–N bonds in benzyl-protected amine amines with O-nosylhydroxylamines via denitrogenation of in situ gen-
erated diazenes enabled by energy-transfer photocatalysis.
derivatives. Very recently, the Xia group reported an interesting
reductive deprotection of benzyl-derived nitrogen groups via
the photochemical mesolytic cleavage of C–N bonds enabled
by an excited phenolate-type photocatalyst (Scheme 44).75 This
protocol is also applicable in the deprotection of benzyl-
derived oxygen-related groups, such as ether, ester and carba-
mate groups. Mechanistically, the excited phenolate-type
photocatalyst’s reducing benzyl ring into a radical anion 348
and the subsequent mesolytic cleavage process play key roles
in the achievement of C–N or C–O bond cleavage.
3.5.4 Energy-transfer photocatalytic cleavage of C–N bonds
in 1,2-dialkyldiazenes in situ generated from primary amines. Scheme 46 Visible-light irradiation enabling an intermolecular C–
In 2023, the Lambert group developed a method for the deami- N/C–C σ-bond metathesis reaction between tertiary amines and
α-diketones.
native C(sp3)–C(sp3) cross-coupling of primary amines with
O-nosylhydroxylamines enabled by an energy-transfer-
mediated photocatalysis using [Ir(dF(CF3)ppy)2(dtbbpy)]PF6
3.5.5 C–N/C–C σ-bond metathesis via homolytic cleavage
(Scheme 45).76 Mechanistically, the reaction initiates from the
under visible light irradiation conditions. Very recently, the Li
in situ generation of 1,2-dialkyldiazenes 347 from primary
and Zeng group described an interesting C–N/C–C σ-bond
amines 344 and O-nosylhydroxylamines 345 in the presence of
metathesis reaction between tertiary amines and α-diketones
atmospheric oxygen. Then energy transfer from the triplet
to access aromatic amides and aryl alkyl ketones in the
state 3[Ir]* to the diazenes can generate the triplet excited state
absence of photosensitizers under the irradiation of visible
of the diazenes. Finally, the occurrence of homolytic C–N bond
light (Scheme 46).77 Mechanistic studies disclosed that the
cleavage in diazenes 354 gives rise to two alkyl radical frag-
simultaneous cleavage and recombination of C–N and C–C
ments (355 and 356) that can recombine to forge (sp3)C–(sp3)C
bonds in intermediates via homolytic fragmentation plays a
bonds, along with the extrusion of a molecule of N2. The
key role in the formation of the target metathesis products.
present protocol provides a novel approach for utilizing readily
available amines as building blocks for the construction of
complex carbon frameworks.
4. Summary and outlook
In summary, in this review, we have overviewed the recent state
of the art of visible-light-driven photocatalytic C–C and C–N
bond cleavage reactions associated with amines and their
derivatives, including cycloalkylamines, tertiary amines,
N-heterocycles, alkyl- or carbonyl-substituted Hantzsch esters,
redox-active imines (RAIs), isonitriles, benzyl-protected amine
derivatives, in situ generated diazenes, etc. All these photo-
catalytic reactions for the cleavage of C–C or C–N bonds
showed relatively mild reaction conditions, more environmen-
tally benign processes, higher selectivity, and broader func-
tional group tolerance in comparison with the traditional
Scheme 44 Reductive mesolytic debenzylation via C–N (or C–O) bond thermal reactions. Despite much advance being made in this
cleavage under visible light photocatalytic conditions. field, several big challenges still exist and need to be overcome:

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 993
 View Article Online

Review Organic Chemistry Frontiers

(1) since the C–C and C–N bond scission may break relevant Acknowledgements
amines and their derivatives into two fragments, both of
which can be used as potential synthons from the viewpoint of We are grateful to the Natural Science Foundation of China
atom economy, making full use of these synthons in organic (No. 22171242) and the Natural Science Foundation of
synthesis has become a big challenge. Currently, most of the Zhejiang Province (No. LY20B020013) for financial support.
reported studies suffer from the utilization of one fragment
only. (2) The research studies on the photocatalytic asymmetric
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

synthesis involving C–C and/or C–N bond cleavage in amines

and their derivatives have still been underdeveloped. The chal- References
lenges lie in the following several factors. Firstly, the elusive
radical species is difficult to control during the formation of 1 (a) C. C. Marvin, Synthesis of Amines and Ammonium
chiral centers; secondly, the design and screening of suitable Salts, Compr. Org. Synth., 2014, 34–99; (b) A. Ricci, Amine
asymmetric ligands is a time-consuming task; thirdly, the Group Chemistry: From Synthesis to the Life Science, Wiley,
precise cooperation between photocatalytic systems and asym- Weinheim, 2008; (c) J. T. Njardarson, Transition-Metal-
metric catalytic systems to create highly enantioselective Catalyzed Rearrangements of Small Cycloalkanes:
centers is also a difficult task to deal with; finally, since the Regioselectivity Trends in β-Carbon Elimination Reactions,
process of C–C or C–N bond cleavage may produce several reac- J. Chem. Educ., 2010, 87, 1348–1349; (d) O. I. Afanasyev,
tive species, avoiding side reactions is a challenging task. E. Kuchuk, D. L. Usanov and D. Chusov, Reductive
Thus, the design of efficient photocatalytic and asymmetric Amination in the Synthesis of Pharmaceuticals, Chem. Rev.,
catalytic systems for the synthesis of valuable chiral com- 2019, 119, 11857–11911.
pounds is still highly desirable. (3) Currently, most of the 2 (a) P. Ruiz-Castillo and S. L. Buchwald, Applications of
reported photocatalytic systems for the cleavage of C–C and/or Palladium-Catalyzed C-N Cross-Coupling Reactions, Chem.
C–N bonds are limited to homogeneous catalytic systems Rev., 2016, 116, 12564–12649; (b) A. Trowbridge,
which have the disadvantages of high catalytic loadings and S. M. Walton and M. J. Gaunt, New Strategies for the
inconvenient recycling. How to develop heterogeneous photo- Transition-Metal Catalyzed Synthesis of Aliphatic Amines,
catalytic systems for the cleavage of C–C and/or C–N bonds Chem. Rev., 2020, 120, 2613–2692; (c) A. Cabre,
remains a challenging task. X. Verdaguer and A. Riera, Recent Advances in the
With the rapid development of visible-light photocatalytic Enantioselective Synthesis of Chiral Amines via Transition
organic synthesis and with even more amines and their deriva- Metal-Catalyzed Asymmetric Hydrogenation, Chem. Rev.,
tives being synthesized or isolated from natural sources, it is 2022, 122, 269–339.
reasonable to expect that the photocatalytic strategies for the 3 (a) A. Biffis, D. Centomo, A. Del Zotto and M. Zecca, Pd
cleavage of C–C and/or C–N bonds in amines and their deriva- Metal Catalysts for Cross-Couplings and Related Reactions
tives will find even broader applicability for the synthesis of in the 21st Century: A Critical Review, Chem. Rev., 2018,
complicated and valuable organic molecules. 118, 2249–2295; (b) L.-J. Cheng and N. P. Mankad, C-C and
C-X coupling reactions of unactivated alkyl electrophiles
using copper catalysis, Chem. Soc. Rev., 2020, 49, 8036–
8064; (c) W. Xue, X. Jia, X. Wang, X. Tao, Z. Yin and
Author contributions H. Gong, Nickel-catalyzed formation of quaternary carbon
centers using tertiary alkyl electrophiles, Chem. Soc. Rev.,
Conceptualization, Y.L. and Q.N.; writing – original draft, Y.L. 2021, 50, 4162–4184.
and Q.N.; writing – review and editing, Q.N., Y.L., Y.Z. and L. 4 (a) Cleavage of Carbon-Carbon Single Bonds by Transition
C.; funding acquisition, Y.L. All authors have given approval to Metals, ed. M. Murakami and N. Chatani, Wiley-VCH,
the final version of the manuscript. Weinheim, 2015, pp. 1–278; (b) Y.-F. Liang, M. Bilal,
L.-Y. Tang, T.-Z. Liang, M. Bilal, L.-Y. Tang, T.-Z. Wang,
Y.-Q. Guan, Z. Cheng, M. Zhu, J. Wei and N. Jiao, Carbon-
Carbon Bond Cleavage for Late-Stage Functionalization,
Data availability Chem. Rev., 2023, 123, 12313–12370, and references cited
No primary research results, software or code have been therein.
included and no new data were generated or analysed as part 5 (a) K. Ouyang, W. Hao, W.-X. Zhang and Z. Xi, Transition-
of this review. Metal-Catalyzed Cleavage of C-N Single Bonds, Chem. Rev.,
2015, 115, 12045–12090; (b) O. Wang, Y. Su, L. Li and
H. Huang, Transition-metal catalysed C-N bond activation,
Chem. Soc. Rev., 2016, 45, 1257–1272.
Conflicts of interest 6 M. D. R. Lutz, S. Roediger, M. A. Rivero-Crespo and
B. Morandi, Mechanistic Investigation of the Rhodium-
There are no conflicts to declare. Catalyzed Transfer Hydroarylation Reaction Involving

994 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

Reversible C-C Bond Activation, J. Am. Chem. Soc., 2023, 14 (a) C. R. J. Stephenson, T. P. Yoon and D. W. C. MacMillan,
145, 26657–26666. Visible Light Photocatalysis in Organic Chemistry, Wiley-VCH,
7 C. Aïssa, Transition-Metal-Catalyzed Rearrangements of Weinheim, Germany, 2018; (b) J. M. R. Narayanam and
Small Cycloalkanes: Regioselectivity Trends in β-Carbon C. R. J. Stephenson, Visible light photoredox catalysis:
Elimination Reactions, Synthesis, 2011, 3389–3407. applications in organic synthesis, Chem. Soc. Rev., 2011, 40,
8 H. Yorimitsu and K. Oshima, Metal-mediated retro-allyla- 102–113; (c) M. H. Shaw, J. Twilton and
tion of homoallyl alcohols for highly selective organic syn- D. W. C. MacMillan, Photoredox Catalysis in Organic
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

thesis, Bull. Chem. Soc. Jpn., 2009, 82, 778–792. Chemistry, J. Org. Chem., 2016, 81, 6898–6926;
9 J. B. Brazier and N. C. O. Tomkinson, Secondary and (d) T. P. Yoon, M. A. Ischay and J. Du, Visible light photoca-
primary amine catalysts for iminium catalysis, Top. Curr. talysis as a greener approach to photochemical synthesis,
Chem., 2010, 291, 281–347. Nat. Chem., 2010, 2, 527–532; (e) C. K. Prier, D. A. Rankic
10 A. Roglans, A. Pla-Quintana and M. Moreno-Manas, and D. W. C. MacMillan, Visible Light Photoredox Catalysis
Diazonium Salts as Substrates in Palladium-Catalyzed with Transition Metal Complexes: Applications in Organic
Cross-Coupling Reactions, Chem. Rev., 2006, 106, 4622– Synthesis, Chem. Rev., 2013, 113, 5322–5363; (f ) Y.-Q. Zou,
4643. J.-R. Chen and W.-J. Xiao, Homogeneous Visible-Light
11 (a) J. García-cárceles, K. A. Bahou and J. Bower, Recent Photoredox Catalysis, Angew. Chem., Int. Ed., 2013, 52,
Methodologies That Exploit Oxidative Addition of C-N 11701–11703; (g) L. Marzo, S. Pagire, O. Reiser and
Bonds to Transition Metals, ACS Catal., 2020, 10, 12738– B. König, Visible-Light Photocatalysis: Does It Make a
12759; (b) E. Wenkert, A.-L. Han and C.-J. Jenny, Nickel- Difference in Organic Synthesis?, Angew. Chem., Int. Ed.,
induced conversion of carbon–nitrogen into carbon– 2018, 57, 10034–10072; (h) N. Romero and D. A. Nicewicz,
carbon bonds. One-step transformations of aryl, quaternary Organic Photoredox Catalysis, Chem. Rev., 2016, 116,
ammonium salts into alkylarenes and biaryls, J. Chem. 10075–10166.
Soc., Chem. Commun., 1988, 975–976; (c) Q. Zeng, F. Li and 15 (a) X.-Y. Yu, J.-R. Chen and W.-J. Xiao, Visible Light-Driven
X. Yin, Transition metal-catalyzed construction of C-X Radical-Mediated C-C Bond Cleavage/Functionalization in
bonds via cleavage of C-N bond of quaternary ammonium Organic Synthesis, Chem. Rev., 2021, 121, 506–561;
salts, AIMS Mol. Sci., 2023, 10, 153–170; (d) X. Chen, (b) W. Yin and X. Wang, Recent advances in iminyl radical-
N.-Z. Wang, Y.-M. Cheng, X. Kong and Z.-Y. Cao, Recent mediated catalytic cyclizations and ring-opening reactions,
Advances in Electro- or Photochemical Driven New J. Chem., 2019, 43, 3254–3264; (c) X. Wu and C. Zhu,
Transformations via Cleavage of the C-N Bond of Recent advances in radical-mediated C-C bond fragmenta-
Quaternary Ammonium Salts, Synthesis, 2023, 2833–2842. tion of non-strained molecules, Chin. J. Chem., 2019, 37,
12 (a) A. R. Katritzky, G. De Ville and R. C. Patel, 171–182; (d) S. A. Morris, J. Wang and N. Zheng, The
Hydrogenation of alkynes with a palladium anchored poly- Prowess of Photogenerated Amine Radical Cations in
styrene catalyst, Tetrahedron, 1981, 37, 25–30; Cascade Reactions: From Carbocycles to Heterocycles, Acc.
(b) J. B. Bapat, R. J. Blade, A. J. Boulton, J. Epsztajn, Chem. Res., 2016, 49, 1957–1968; (e) J. Xuan, Z.-G. Zhang
A. R. Katritzky, J. Lewis, P. Molina-Buendia, P.-L. Nie and and W.-J. Xiao, Visible-Light-Induced Decarboxylative
C. A. Ramsden, Pyridines as leaving groups in synthetic Functionalization of Carboxylic Acids and Their
transformations: Nucleophilic displacements of amino Derivatives, Angew. Chem., Int. Ed., 2015, 54, 15632–15641;
groups, and novel preparations of nitriles and isocyanates, (f) D. M. Kitcatt, S. Nicolle and A.-L. Lee, Direct decarboxy-
Tetrahedron Lett., 1976, 17, 2691–2694; (c) F. He, S. Ye and lative Giese reactions, Chem. Soc. Rev., 2022, 51, 1415–1453;
J. Wu, Recent Advances in Pyridinium Salts as Radical (g) L. McMurray, T. M. McGuire and R. L. Howells, Recent
Reservoirs in Organic Synthesis, ACS Catal., 2019, 9, 8943– Advances in Photocatalytic Decarboxylative Coupling
8960; (d) J. T. M. Correia, V. A. Fernandes, B. T. Matsuo, Reactions in Medicinal Chemistry, Synthesis, 2020, 1719–
J. A. C. Delgado, W. C. de Souza and M. W. Paixao, 1737; (h) Y. Xu, H. Chen, L. Yu, X. Peng, J. Zhang, Z. Xing,
Photoinduced deaminative strategies: Katritzky salts as Y. Bao, A. Liu, Y. Zhao, C. Tian, Y. Liang and X. Huang, A
alkyl radical precursors, Chem. Commun., 2020, 56, 503– light-driven enzymatic enantioselective radical acylation,
514; (e) F. J. R. Klauck, M. J. James and F. Glorius, Nature, 2024, 625, 74–78; (i) K. Jia and Y. Chen, Visible-
Deaminative Strategy for the Visible-Light-Mediated light-induced alkoxyl radical generation for inert chemical
Generation of Alkyl Radicals, Angew. Chem., Int. Ed., 2017, bond cleavage/functionalization, Chem. Commun., 2018, 54,
56, 12336–12339. 6105–6112; ( j) Z. Zuo, Photocatalytic alkoxy radical-
13 (a) P. T. Anastas and M. M. Kirchhoff, Origins, current mediated transformations, Tetrahedron Lett., 2018, 59,
status, and future challenges of green chemistry, Acc. 2103–2111; (k) H.-H. Li, J.-Q. Li, X. Zheng and P.-Q. Huang,
Chem. Res., 2002, 35, 686–693; (b) R. Sheldon, I. Arends and Photoredox-Catalyzed Decarboxylative Cross-Coupling of
U. Hanefeld, Green Chemistry and Catalysis, Wiley-VCH, α-Amino Acids with Nitrones, Org. Lett., 2021, 23, 876–880;
Weinheim, 2007, pp. 1–5; (c) P. T. Anasta and J. C. Waner, (l) G.-Q. Li, F.-R. Meng, W.-J. Xiao and J.-R. Chen,
Green Chemistry: Theory and Practice, Oxford University Photoinduced copper-catalyzed asymmetric radical three-
Press, Oxford, 1998. component cross-coupling of 1,3-enynes with oxime esters

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 995
 View Article Online

Review Organic Chemistry Frontiers

and carboxylic acid, Org. Chem. Front., 2023, 10, 2773–2781; pp. 93–128; (b) J. Xuan and W. Xiao, Visible-Light
(m) S. Yang, L. Wang, L. Wang and H. Li, Visible-Light Photoredox Catalysis, Angew. Chem., Int. Ed., 2012, 51,
Photoredox-Catalyzed Regioselective Sulfonylation of 6828–6838; (c) J. M. R. Narayanam and C. R. J. Stephenson,
Alkenes Assisted by Oximes via [1,5]-H Migration, J. Org. Visible light photoredox catalysis: applications in organic
Chem., 2020, 85, 564–573. synthesis, Chem. Soc. Rev., 2011, 40, 102–113; (d) L. Shi and
16 (a) M. A. Ischay, M. E. Anzovino, J. Du and T. P. Yoon, W. Xia, Photoredox functionalization of C-H bonds adja-
Efficient Visible Light Photocatalysis of [2+2] Enone cent to a nitrogen atom, Chem. Soc. Rev., 2012, 41, 7687–
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

Cycloadditions, J. Am. Chem. Soc., 2008, 130, 12886–12887; 7697; (e) A. G. Condie, G. J. Conzález-Gómez and
(b) J. M. R. Narayanam, J. W. Tucker and C. R. J. Stephenson, Visible-Light Photoredox Catalysis:
C. R. J. Stephenson, Electron-Transfer Photoredox Aza-Henry Reactions via C-H Functionalization, J. Am.
Catalysis: Development of a Tin-Free Reductive Chem. Soc., 2010, 132, 1464–1465.
Dehalogenation Reaction, J. Am. Chem. Soc., 2009, 131, 21 (a) W. Huang and X. Cheng, Hantzsch Esters as
8756–8757; (c) S.-P. Luo, E. Mejía, A. Friedrich, A. Pazidis, Multifunctional Reagents in Visible-Light Photoredox
H. Junge, A. E. Surkus, R. Jackstell, S. Denurra, S. Gladiali, Catalysis, Synlett, 2017, 148–158; (b) P.-Z. Wang, J.-R. Chen
S. Lochbrunner and M. Beller, Photocatalytic Water and W.-J. Xiao, Hantzsch esters: an emerging versatile class
Reduction with Copper-Based Photosensitizers: A Noble- of reagents in photoredox catalyzed organic synthesis, Org.
Metal-Free System, Angew. Chem., Int. Ed., 2013, 52, 419– Biomol. Chem., 2019, 17, 6936–6951.
423. 22 O. O. Sokolova and J. F. Bower, Selective Carbon-Carbon
17 (a) L. Capaldo, D. Ravelli and M. Fagnoni, Direct Bond Cleavage of Cyclopropylamine Derivatives, Chem.
Photocatalyzed Hydrogen Atom Transfer (HAT) for Rev., 2021, 121, 80–109.
Aliphatic C-H Bonds Elaboration, Chem. Rev., 2022, 122, 23 (a) S. Maity, M. Zhu, R. S. Shinabery and N. Zheng,
1875–1924; (b) J. D. Bell and J. A. Murphy, Recent advances Intermolecular [3+2] Cycloaddition of Cyclopropylamines
in visible light-activated radical coupling reactions trig- with Olefins by Visible-Light Photocatalysis, Angew. Chem.,
gered by (i) ruthenium,(II) iridium and (iii) organic photo- Int. Ed., 2012, 51, 222–226; (b) T. H. Ngugen, S. Maity and
redox agents, Chem. Soc. Rev., 2021, 50, 9540–9685. N. Zheng, Visible light mediated intermolecular [3 + 2]
18 (a) B. Górski, A.-L. Barthelemy, J. J. Douglas, F. Juliá and annulation of cyclopropylanilines with alkynes, Beilstein
D. Leonori, Copper-catalysed amination of alkyl iodides J. Org. Chem., 2014, 10, 975–980; (c) T. H. Nguyen,
enabled by halogen-atom transfer, Nat. Catal., 2021, 4, S. A. Morris and N. Zheng, Intermolecular [3+2] Annulation
623–630; (b) T. Constantin, F. Juliá, N. S. Sheikh and of Cyclopropylanilines with Alkynes, Enynes, and Diynes
D. Leonori, A case of chain propagation: α-aminoalkyl rad- via Visible Light Photocatalysis, Adv. Synth. Catal., 2014,
icals as initiators for aryl radical chemistry, Chem. Sci., 356, 2831–2837.
2020, 11, 12822–12828; (c) T. Constantin, M. Zanini, 24 (a) J. Wang and N. Zheng, The cleavage of a C-C Bond in
A. Regni, N. S. Shelikh, F. Juliá and D. Leonori, Aminoalkyl cyclobutylanilines by visible-light photoredox catalysis:
radicals as halogen-atom transfer agents for activation of Development of a [4+2] annulation method, Angew. Chem.,
alkyl and aryl halides, Science, 2020, 367, 1021–1026; Int. Ed., 2015, 54, 11424–11427; (b) J. Wang, T. H. Nguyen
(d) R. K. Neff, Y.-L. Su, S. Liu, M. Rosado, X. Zhang and and N. Zheng, Photoredox-catalyzed [4+2] annulation of
M. P. Doyle, Generation of Halomethyl Radicals by cyclobutylanilines with alkenes, alkynes, and diynes in con-
Halogen Atom Abstraction and Their Addition Reactions tinuous flow, Sci. China: Chem., 2016, 59, 180–183.
with Alkenes, J. Am. Chem. Soc., 2019, 141, 16643–16650; 25 L. Chen, Y. Li, M. Han, Y. Peng, X. Chen, S. Xiang, H. Gao,
(e) Y.-L. Su, L. Tram, D. Wherritt, H. Arman, W. P. Griffith T. Lu, S. P. Luo, B. Zhou, H. Wu, Y. F. Yang and Y. Liu,
and M. P. Doyle, α-Amino Radical-Mediated Diverse P/N-Heteroleptic Cu(I)-Photosensitizer-Catalyzed [3 + 2]
Difunctionalization of Alkenes: Construction of C-C, C-N, Regiospecific Annulation of Aminocyclopropanes and
and C-S Bonds, ACS Catal., 2020, 10, 13682–13687. Functionalized Alkynes, J. Org. Chem., 2022, 87, 15571–
19 (a) K. Nakajima, Y. Miyake and Y. Nishibayashi, Synthetic 15581.
Utilization of α-Aminoalkyl Radicals and Related Species in 26 (a) D. Uraguchi, Y. Kimura, F. Ueoka and T. Ooi, Urea as a
Visible Light Photoredox Catalysis, Acc. Chem. Res., 2016, Redox-Active Directing Group under Asymmetric
49, 1946–1956; (b) S. Zhu, A. Das, L. Bui, H. Zhou, Photocatalysis of Iridium-Chiral Borate Ion Pairs, J. Am.
D. P. Curran and M. Rueping, Oxygen Switch in Visible- Chem. Soc., 2020, 142, 19462–19467; (b) Y. Kimura,
Light Photoredox Catalysis: Radical Additions and D. Uraguchi and T. Ooi, Catalytic asymmetric synthesis of
Cyclizations and Unexpected C-C-Bond Cleavage Reactions, 5-membered alicyclic α-quaternary β-amino acids via [3 +
J. Am. Chem. Soc., 2013, 135, 1823–1829; (c) S. M. Thullen 2]-photocycloaddition of α-substituted acrylates, Org.
and T. Rovis, A Mild Hydroaminoalkylation of Conjugated Biomol. Chem., 2021, 19, 1744–1747; (c) Y. Yin, Y. Li,
Dienes Using a Unified Cobalt and Photoredox Catalytic T. P. Gonçalves, Q. Zhan, G. Wang, X. Zhao, B. Qiao,
System, J. Am. Chem. Soc., 2017, 139, 15504–15508. K.-W. Huang and Z. Jiang, All-Carbon Quaternary
20 (a) Y. Zou and W. Xiao, Visible Light Mediated α-Amino C-H Stereocenters α to Azaarenes via Radical-Based Asymmetric
Functionalization Reactions, Wiley-VCH, Berlin, 2018, ch 4, Olefin Difunctionalization, J. Am. Chem. Soc., 2020, 142,

996 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

19451–19456; (d) Y. Dai, S. Liang, G. Zeng, H. Huang, Generation of Iminium Ions and Amino Radicals, Angew.
X. Zhao, S. Cao and Z. Jiang, Asymmetric [3 + 2] photocy- Chem., Int. Ed., 2012, 51, 8050–8053.
cloadditions of cyclopropylamines with electron-rich and 33 B. Lipp, A. Lipp, H. Detert and T. Opatz, Light-Induced
electron-neutral olefins, Chem. Sci., 2022, 13, 3787–3795; Alkylation of (Hetero)aromatic Nitriles in a
(e) Y. Dai, H. Huang, S. Liang, Y. Yin, X. Ban, X. Zhao and TransitionMetal-Free C-C-Bond Metathesis, Org. Lett., 2017,
Z. Jiang, Catalytic Asymmetric Intermolecular [3 + 2] 19, 2054–2057.
Photocycloaddition of Cyclopropylamines with Electron- 34 Y. Zhao, C. Empel, W. Liang, R. M. Koenigs and
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

Deficient Olefins, Org. Lett., 2003, 25, 4551–4555; F. W. Patureau, Gem-Difluoroallylation of Aryl Sulfonium
(f) L. Mollari, M. A. Valle-Anores, A. M. Martínez-Gualda, Salts, Org. Lett., 2022, 24, 8753–8758.
L. Marzo, A. Fraile and J. Aleman, Asymmetric synthesis of 35 J. B. Beatty and C. R. J. Stephenson, Synthesis of
cyclic β-amino carbonyl derivatives by a formal [3+2] photo- (-)-Pseudotabersonine, (-)-Pseudovincadifformine, and
cycloaddition, Chem. Commun., 2002, 58, 1334–1337. (+)-Coronaridine Enabled by Photoredox Catalysis in Flow,
27 D. Staveness, T. M. Sodano, K. Li, E. A. Burnham, J. Am. Chem. Soc., 2014, 136, 10270–10273.
K. D. Jackson and C. R. J. Stephenson, Providing a New 36 J. Qiao, W. Zhao, Y. Liang, Z.-J. Yao and S. Wang,
Aniline Bioisostere through the Photochemical Production Diastereoselective Access to Tetracyclic Eight-Membered
of 1-Aminonorbornanes, Chem, 2019, 5, 215–226. Lactams through a Dearomative Heck Reaction and an
28 A. R. Allen, A. E. Tharp and C. R. J. Stephenson, A formal Alkylative Ring-Opening Driven by Photoexcited
(3+2) cycloaddition strategy toward 2-azanorbornanes, Spiroindolines, Chem. – Eur. J., 2021, 27, 6308–6314.
ChemRxiv, 2022, preprint, DOI: 10.26434/chemrxiv-2022- 37 D. Mazzarella, T. Bortolato, G. Pelosi and L. Dell’Amico,
42h36. Photocatalytic (3 + 2) dipolar cycloadditions of aziridines
29 Y. Zheng, W. Huang, R. K. Dhungana, A. Granados, driven by visible-light, Chem. Sci., 2023, 15, 271–277.
S. Keess, M. Makvandi and G. A. Molander, Photochemical 38 A. L. Ruiz, M. L. Mantia, D. Merli, S. Protti and M. Fagnoni,
Intermolecular [3σ + 2σ]-Cycloaddition for the Alkyl Radical Generation via C-C Bond Cleavage in
Construction of Aminobicyclo[3.1.1]heptanes, J. Am. Chem. 2-Substituted Oxazolidines, ACS Catal., 2022, 12, 12469–
Soc., 2022, 144, 23685–23690. 12476.
30 (a) X. Zhang, Y. Wang, J. Liu, C. Tian, X. Li, P. Xie, Z. Zhu 39 X.-Y. Lv, A. Abrams and R. Martin, Dihydroquinazolinones
and T. Yao, Synthesis of 3-aminotetrahydro-1H-carbazols as adaptative C(sp3) handles in arylations and alkylations
by visible-light photocatalyzed cycloaddition of cyclopropyl- via dual catalytic C-C bond-functionalization, Nat.
anilines with 2-alkenylarylisocyanides, Chem. Commun., Commun., 2022, 13, 2394–2401.
2023, 59, 14423–14426; (b) J. Qiu, W. Li, X. Li, Y. Cao, 40 G. Li, R. Chen, L. Wu, Q. Fu, X. Zhang and Z. Tang, Alkyl
C.-X. Pan and H. Li, Radical-Based cis-Selective Transfer from C-C Cleavage, Angew. Chem., Int. Ed., 2013,
Annulations of N,N’-Cyclic Azomethine Imines with 52, 8432–8436.
N-Sulfonyl Cyclopropylamines, Org. Lett., 2023, 25, 8000– 41 (a) W. Chen, Z. Liu, J. Tian, J. Li, J. Ma, X. Cheng and G. Li,
8004; (c) S. Li and L. Zhou, Photocatalytic (3 + 3) Building Congested Ketone: Substituted Hantzsch Ester
Annnulation of Vinyldiazo Compounds and and Nitrile as Alkylation Reagents in Photoredox Catalysis,
Aminocyclopropanes, Org. Lett., 2024, 26, 3294–3298. J. Am. Chem. Soc., 2016, 138, 12312–12315; (b) K. Nakajima,
31 (a) M. Wakioka, H. Morita, N. Ichihara, M. Saito, I. Osaka and S. Nojima, K. Sakata and Y. Nishibayashi, Visible-Light-
F. Ozawa, Mixed-Ligand Approach to Palladium-Catalyzed Mediated Aromatic Substitution Reactions of Cyanoarenes
Direct Arylation Polymerization: Synthesis of Donor-Acceptor with 4-Alkyl-1,4-dihydropyridines through Double Carbon-
Polymers Containing Unsubstituted Bithiophene Units, Carbon Bond Cleavage, ChemCatChem, 2016, 8, 1028–1032;
Macromolecules, 2020, 53, 158–164; (b) E. D. Silva, (c) E. Gandolfo, X. Tang, S. R. Roy and P. Melchiorre,
O. A. L. Alves, R. T. Ribeiro, R. C. R. Chagas, J. A. F. P. Villar Photochemical Asymmetric Nickel-Catalyzed Acyl Cross-
and J. L. Princival, Homogeneous CuCl2/TMEDA/ Coupling, Angew. Chem., Int. Ed., 2019, 58, 16854–16858.
TEMPO-Catalyzed chemoselective base- and halogen-free 42 F. Gu, W. Huang, X. Liu, W. Chen and X. Cheng,
aerobic oxidation of primary alcohols in mild conditions, Substituted Hantzsch Esters as Versatile Radical Reservoirs
Appl. Catal., A, 2021, 623, 118289; (c) K. Verebelyi and B. Ivan, in Photoredox Reactions, Adv. Synth. Catal., 2017, 360, 925–
Cationic polymerization of styrene by the TiCl4/N,N,N′,N’-tetra- 931.
methylethylenediamine(TMEDA) catalyst system in benzotri- 43 (a) K. Nakajima, S. Nojima and Y. Nishibayashi, Nickel-
fluoride, an environmentally benign solvent, at room tempera- and Photoredox-Catalyzed Cross-Coupling Reactions of Aryl
ture, Polymer, 2012, 53, 3426–3431; (d) D. Baskaran, Halides with 4-Alkyl-1,4-dihydropyridines as Formal
A. H. E. Muller and S. Sivaram, The effect of TMEDA on the Nucleophilic Alkylation Reagents, Angew. Chem., Int. Ed.,
kinetics of the anionic polymerization of methyl methacrylate 2016, 55, 14106–14110; (b) X. Wang, H. Li, G. Qiu and
in tetrahydrofuran using lithium as counterion, Macromol. J. Wu, Substituted Hantzsch esters as radical reservoirs
Chem. Phys., 2000, 201, 1901–1911. with the insertion of sulfur dioxide under photoredox cata-
32 S. Cai, X. Zhao, X. Wang, Q. Liu, Z. Li and D. Z. Wang, lysis, Chem. Commun., 2019, 55, 2062–2065; (c) Y. Liu,
Visible-Light-Promoted C-C Bond Cleavage: Photocatalytic Z. Zhang, Z. Wei, Z. Zhong, S. Liu, Y. Yang and X. Zeng,

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 997
 View Article Online

Review Organic Chemistry Frontiers

Catalyst-free photochemical reactions of alkyl dihydropyri- (n) A. V. Bay, K. P. Fitzpatrick, G. A. Gonzalez-Montiel,

dines via modulation of chromophores and light wave- A. O. Farah, P. H.-Y. Cheong and K. A. Scheidt, Light-Driven
length, New J. Chem., 2023, 47, 7369–7374. Carbene Catalysis for the Synthesis of Aliphatic and
44 (a) X. Jiang, W. Xiong, S. Deng, F.-D. Lu, Y. Jia, Q. Yang, α-Amino Ketones, Angew. Chem., Int. Ed., 2021, 60, 17925–
L.-Y. Xue, X. Qi, J. A. Tunge, L.-Q. Lu and W.-J. Xiao, 17931; (o) Z. Yao, J. Yang, Z. Luo, H. Wang, X. Zhang, J. Ye,
Construction of axial chirality via asymmetric radical trap- L. Xu and Q. Shi, Photo-driven metal-free multicomponent
ping by cobalt under visible light, Nat. Catal., 2022, 5, 788– reaction between aldehydes, anilines and 4-substituted-
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

797; (b) X. Song, Y. Zhang, Y. Li, X. Zhao, Y. Yin, X. Ban and DHPs for the synthesis of secondary amines, Green Chem.,
Z. Jiang, Catalytic asymmetric synthesis of azaarene-func- 2022, 24, 7968–7973; ( p) X. Wang, Y. Tang, S. Ye, J. Zhang,
tionalized tertiary amines and α-amino acid derivatives Y. Kuang and J. Wu, Access to Sulfoxides under NHC/
from E/Z-ketimine mixtures via enantioselective radical Photocatalysis via a Radical Pathway, Org. Lett., 2022, 24,
coupling, ACS Catal., 2023, 13, 6396–6402; (c) T. Li, L. Luo, 2059–2063; (q) L. Li, S.-Q. Zhang, Y. Chen, X. Cui, G. Zhao,
X. Cheng and Z. Lu, Enantioconvergent Cross-Coupling Z. Tang and G.-X. Li, Photoredox Alkylation of
Reaction with 1,4-Dihydropyridine Derivatives via Sulfinylamine Enables the Synthesis of Highly
Photoinduced Nickel Catalysis, ACS Catal., 2024, 14, 3278– Functionalized Sulfinamides and S(VI) Derivatives, ACS
3286; (d) R.-X. Wang, P. Yang, Y.-Z. Cheng and S.-L. You, Catal., 2022, 12, 15334–15340; (r) P. Ghosh, N. Y. Kwon,
Rh-Catalyzed Asymmetric Allylic Substitution with Photo- Y. Byun, N. K. Mishra, J. S. Park and I. S. Kim, Cobalt(II)-
Generated Alkyl Radical Species, ACS Catal., 2024, 14, Catalyzed C-H Alkylation of N-Heterocycles with 1,4-
12403–12409; (e) J. L. Shwarz, H.-M. Huang, T. O. Paulisch Dihydropyridines, ACS Catal., 2022, 12, 15707–15714;
and F. Glorius, Stereoretentive Catalytic [3+2] (s) K. B. Pal, E. M. D. Tommaso, A. K. Inge and B. Olofsson,
Cycloaddition/Rearrangement/Decarboxylation Reactions Stereospecific Photoredox-Catalyzed Vinylation to
of Indoles with Non-Racemic Donor-Acceptor Functionalized Alkenes and C-Glycosides, Angew. Chem.,
Cyclopropanes, ACS Catal., 2020, 10, 1621–1627; Int. Ed., 2023, 62, e202301368; (t) J. Liu, W. Zhang, X. Tao,
(f) R. A. Angnes, C. Potnis, S. Liang, C. R. D. Correia and Q. Wang, X. Wang, Y. Pan, J. Ma, L. Yan and Y. Wang,
G. B. Hammond, Photoredox-Catalyzed Synthesis of Photoredox microfluidic synthesis of trifluoromethylated
Alkylaryldiazenes: Formal Deformylative C-N Bond amino acids, Org. Lett., 2023, 25, 3083–3088; (u) L. L. Yan,
Formation with Alkyl Radicals, J. Org. Chem., 2020, 85, T.-Z. Zhang, Z.-Z. Lv and M.-C. Fu, Photoinduced defluori-
4153–4164; (g) H.-W. Du, J. Sun, Q.-S. Gao, J.-Y. Wang, native alkylation of trifluoromethyl alkenes with carbonyl
H. Wang, Z. Xu and M.-D. Zhou, Synthesis of derivatives by C-C bond scission, Org. Chem. Front., 2023,
Monofluoroalkenes through Visible-Light-Promoted 10, 6205–6211; (v) H. Li, S. Li, H. Hu, R. Sun, M. Liu,
Defluorinative Alkylation of gem-Difluoroalkenes with A. Ding, X. Liu, W. Luo, Z. Fu, S. Guo and H. Cai, Visible-
4-Alkyl-1,4-dihydropyridines, Org. Lett., 2020, 22, 1542– light-induced C(sp3)-C(sp3) bond formation via radical/
1546; (h) A. V. Bay, K. P. Fitzpatrick, R. C. Betori and radical cross-coupling, Chem. Commun., 2023, 59, 1205–
K. A. Scheidt, Combined Photoredox and Carbene Catalysis 1208; (w) S. Patel, A. Chakrabort and I. Chatterjee, C(sp3)-C
for the Synthesis of Ketones from Carboxylic Acids, Angew. (sp3) Radical-Cross-Coupling Reaction via Photoexcitation,
Chem., Int. Ed., 2020, 59, 9143–9148; (i) X.-K. He, J. Lu, Org. Lett., 2023, 25, 8246–8251; (x) Q. Li, L.-C. Wang,
A.-J. Zhang, Q.-Q. Zhang, G.-Y. Xu and J. Xuan, BI-OAc- Z.-P. Bao and X.-F. Wu, Photoredox-catalyzed carbonylative
Accelerated C3-H Alkylation of Quinoxalin-2(1H)-ones acylation of styrenes with Hantzsch esters, Chem. Commun.,
under Visible-Light Irradiation, Org. Lett., 2020, 22, 5984– 2024, 60, 4656–4658.
5989; ( j) Y. Zhang, Y. Tanabe, S. Kuriyama and 45 F. Gu, W. Huang, X. Liu, W. Chen and X. Cheng, Substituted
Y. Nishibayashi, Cooperative Photoredox- and Nickel- Hantzsch Esters as Versatile Radical Reservoirs in Photoredox
Catalyzed Alkylative Cyclization Reactions of Alkynes with Reactions, Adv. Synth. Catal., 2018, 360, 925–931.
4-Alkyl-1,4-dihydropyridines, J. Org. Chem., 2021, 86, 46 (a) L. Marchini, J. A. C. Velez, E. Elias, J. T. M. Correia,
12577–12590; (k) X. Wang, R. Liu, Q. Ding, W. Xiao and S. Moura and M. W. Paixão, Organophotocatalytic
J. Wu, Synergistic photoredox and tertiary amine catalysis: Carbamoylation of Morita-Baylis-Hillman Carbonates, Adv.
generation of allylic sulfones from Morita-Baylis-Hillman Synth. Catal., 2024, 366, 2063–2071; (b) Z. Zhong, H. Wu,
acetates and sulfur dioxide, Org. Chem. Front., 2021, 8, X. Chen, Y. Luo, L. Yang, X. Feng and X. Liu, Visible Light-
3308–3313; (l) Y. Liu, W. Luo, T. Xia, Y. Fang, C. Du, X. Jin, Promoted Enantioselective Acylation and Alkylation of
Y. Li, L. Zhang, W. Lei and H. Wu, Merging radical-polar Aldimines Enabled by 9-Fluorenone Electron-Shuttle
crossover/cycloisomerization processes: access to polyfunc- Catalysis, J. Am. Chem. Soc., 2024, 146, 20401–20413;
tional furans enabled by metallaphotoredox catalysis, Org. (c) K. B. Vega, A. L. C. de Oliveira, B. Konig and
Chem. Front., 2021, 8, 1732–1738; (m) S.-C. Ren, W.-X. Lv, M. W. Paixão, Visible-Light-Induced Synthesis of 1,2-
X. Yang, J.-L. Yan, J. Xu, F.-X. Wang, L. Hao, H. Chai, Z. Jin Dicarboxyl Compounds from Carbon Dioxide, Carbamoyl-
and Y. R. Chi, Carbene-Catalyzed Alkylation of Carboxylic dihydropyridine, and Styrene, Org. Lett., 2024, 26, 860–865;
Esters via Direct Photoexcitation of Acyl Azolium (d) Z. Zhang, J. Wang, C. Yu, J. Tan, H. Du and N. Chen,
Intermediates, ACS Catal., 2021, 11, 2925–2934; Visible-Light-Induced Acylative Pyridylation of Styrenes,

998 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025
 View Article Online

Organic Chemistry Frontiers Review

Org. Lett., 2024, 26, 4727–4732; (e) P. H. R. Oliveira, Photochemical Divergent Ring-Closing Metathesis of 1,7-
E. Tordato, J. A. C. Velez, P. S. Carneiro and M. W. Paixão, Enynes: Efficient Synthesis of Spirocyclic Quinolin-2-ones,
Visible-Light Mediated Carbamoylation of Nitrones under a Org. Lett., 2024, 26, 6664–6669.
Continuous Flow Regime, J. Org. Chem., 2023, 88, 6407– 49 (a) W. Ji, P. Li, S. Yang and L. Wang, Visible-light-induced
6419; (f) T. Singh, G. C. Upreti, A. Arora, H. Chauhan and oxidative formylation of N-alkyl-N-( prop-e-yn-1-yl)anilines
A. Singh, Visible Light-Mediated Carbamoylation of para- with molecular oxygen in the absence of an external photo-
Quinone Methides, J. Org. Chem., 2023, 88, 2784–2791; senistizer, Chem. Commun., 2017, 53, 8482–8485;
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

(g) X. Shan, X. Wang, E. Chen, J. Liu, K. Lu and X. Zhao, (b) S. Yang, P. Li, Z. Wang and L. Wang, Photoinduced oxi-
Visible-Light-Promoted Trifluoromethylthiolation and dative formylation of N,N-dimethylanilines with molecular
Trifluoromethylselenolation of 1,4-Dihydropyridines, oxygen without external photocatalyst, Org. Lett., 2017, 19,
J. Org. Chem., 2023, 88, 319–328; (h) L. Cardinale, 3386–3389.
M.-O. W. S. Schmotz, M. O. Konev and A. J. von Wangelin, 50 X. Li, X. Gu, Y. Li and P. Li, Aerobic Transition-Metal-Free
Photoredox-Catalyzed Synthesis of α-Amino Acid Amides by Visible-Light Photoredox Indole C-3 Formylation Reaction,
Imine Carbamoylation, Org. Lett., 2022, 24, 506–510; ACS Catal., 2104, 4, 1897–1900.
(i) B. T. Mastuo, P. H. R. Oliveira, J. T. M. Correia and 51 N. Iqbal and E. J. Cho, Formation of Carbonyl Compounds
M. W. Paixão, Carbamoylation of Azomethine Imines via from Amines through Oxidative C-N Bond Cleavage using
Visible-Light Photoredox Catalysis, Org. Lett., 2021, 23, Visible Light Photocatalysis and Applications to N-PMB-Amide
6775–6779; ( j) L. Cardinale, M. O. Konev and A. J. von Deprotection, Adv. Synth. Catal., 2015, 357, 2187–2192.
Wangelin, Photoredox-Catalyzed Addition of Carbamoyl 52 C. Gu, S. Wang, Q. Zhang and J. Xie, Visible-light-mediated
Radicals to Olefins: A 1,4-Dihydropyridine Approach, Chem. amidation from carboxylic acids and tertiary amines via C–
– Eur. J., 2020, 26, 8239–8243; (k) N. Alandini, L. Buzzetti, N cleavage, Chem. Commun., 2022, 58, 5873–5876.
G. Favi, T. Schulte, L. Candish, K. D. Collins and 53 X. Zhang, Y. Shen and T. Rovis, Photoinduced Nickel-
P. Melchiorre, Amide Synthesis by Nickel/Photoredox- Catalyzed Selective N-Demethylation of Trialkylamines
Catalyzed Direct Carbamoylation of (Hetero)Aryl Bromides, Using C(sp2)-Bromides as HAT Reagents, J. Am. Chem. Soc.,
Angew. Chem., Int. Ed., 2020, 59, 5248–5253. 2023, 145, 3294–3300.
47 (a) F. Tureček and R. R. Julian, Peptide Radicals and Cation 54 A. Arumugam and G. C. Senadi, Visible-light photocata-
Radicals in the Gas Phase, Chem. Rev., 2013, 113, 6691– lyzed C–N bond activation of tertiary amines: a three-com-
6733; (b) R. A. Zubarev, N. L. Kelleher and F. W. Mclafferty, ponent approach to synthesize quinazolines, Org. Biomol.
Electron Capture Dissociation of Multiply Charged Protein Chem., 2024, 22, 1245–1253.
Cations. A Nonergodic Process, J. Am. Chem. Soc., 1998, 55 A. Shiozuka, K. Sekine and Y. Kuninobu, Photoinduced
120, 3265–3266; (c) N. Neerathilingam, M. B. Reddy and Deaminative Borylation of Unreactive Aromatic Amines
R. Anandhan, Regioselective Synthesis of 2° Amides Using Enhanced by CO2, Org. Lett., 2021, 23, 4774–4778.
Visible-Light-Induced Photoredox-Catalyzed Nonaqueous 56 S. Ji, S. Qin, C. Yin, L. Luo and H. Zhang, Unreactive C-N
Oxidative C-N Cleavage of N,N-Dibenzylanilines, J. Org. Bond Activation of Anilines via Photoinduced Aerobic
Chem., 2021, 86, 15117–15127. Borylation, Org. Lett., 2022, 24, 64–68.
48 (a) P. F. Yuan, Z. Yang, S. S. Zhang, C. M. Zhu, X. L. Yang 57 J.-Y. Liang, Y.-W. Sun and Y.-Q. Zou, Photochemical reduc-
and Q. Y. Meng, Deconstructive Carboxylation of Activated tive deamination of alpha-amino aryl alkyl ketones, Chem.
Alkenes with Carbon Dioxide, Angew. Chem., Int. Ed., 2024, Commun., 2023, 59, 14685–14688.
63, e202313030; (b) K.-G. Cao, T.-Y. Gao, L.-L. Liao, 58 F. Liu, Z.-P. Ye, Y.-Z. Hu, J. Gao, L. Zheng, K. Chen,
C.-K. Ran, Y.-X. Jiang, W. Zhang, Q. Zhou, J.-H. Ye, Y. Lan H.-Y. Xiang, X.-Q. Chen and H. Yang, N,N,N′,N′-
and D.-G. Yu, Photocatalytic carboxylation of styrenes with Tetramethylethylene-diamine-Enabled
CO2 via C=C double bond cleavage, Chin. J. Catal., 2024, 56, PhotoredoxCatalyzed C-H Methylation of N-Heteroarenes,
74–80; (c) Y. Peng, H. Bao, L. Zheng, Y. Zhou, Q. Ni, J. Org. Chem., 2021, 86, 11905–11914.
X. Chen, Y. Li, P. Yan, Y.-F. Yang and Y. Liu, Cu(I)- 59 Y. Meng, C. Pan, N. Liu, H. Li, Z. Liu, Y. Deng, Z. Wei, J. Xu
Photosensitizer-Catalyzed Olefin-α-Amino Radical and B. Fan, Photocatalytic synthesis of 2,3-diamines from
Metathesis/Demethylenative Cyclization of 1,7-Enynes, Org. anilines and DIPEA via C-N bond cleavage and C-C bond
Lett., 2024, 26, 3218–3223; (d) Q. Jiang, H. Bao, Y. Peng, formation, Green Chem., 2024, 26, 300–305.
Y. Zhou, L. Chen and Y. Liu, Demethylenative cyclization of 60 S. Mondal, A. M. Pandey and B. Gnanaprakasam, Visible
1,7-enynes using a-amino radicals as a traceless initiator Light Mediated Organophotoredox Catalyzed Synthesis of
enabled by Cu(I)-photosensitizers, Chem. Commun., 2024, Tetraketones Using Tertiary Amines as Alkyl Synthons,
60, 6399–6402; (e) G. C. Upreti, T. Singh, K. Khanna, J. Org. Chem., 2024, 89, 3769–3780.
D. Sahoo and A. Singh, Photocatalytic, α-Aminoalkyl 61 H. Bao, B. Zhou, S.-P. Luo, Z. Xu, H. Jin and Y. Liu, P/N
Radical-Mediated, MethyleneExtrusive Ring-Closing Heteroleptic Cu(I)-Photosensitizer-Catalyzed Deoxygenative
Transformation of o-Alkynyl and o-Cyano Acrylamides, Org. Radical Alkylation of Aromatic Alkynes with Alkyl
Lett., 2024, 26, 3652–3656; (f) W.-T. Li, Z.-X. Zhang, Aldehydes Using Dipropylamine as a Traceless Linker
J. Huang, H.-M. Jiang, Z.-W. Luo, J.-H. Li and X.-H. Ouyang, Agent, ACS Catal., 2020, 10, 7563–7572.

This journal is © the Partner Organisations 2025 Org. Chem. Front., 2025, 12, 975–1000 | 999
 View Article Online

Review Organic Chemistry Frontiers

62 L. Zheng, Q. Jiang, H. Bao, B. Zhou, S. P. Luo, H. Jin, 70 L. Huang, R. Kancherla and M. Rueping, Nickel Catalyzed
H. Wu and Y. Liu, Tertiary Amines Acting as Alkyl Radical Regiodivergent Cross-Coupling Alkylation of Aryl Halides
Equivalents Enabled by a P/N Heteroleptic Cu(I) with Redox-Active Imines, ACS Catal., 2022, 12, 11563–
Photosensitizer, Org. Lett., 2020, 22, 8888–8893. 11572.
63 H. Bao, L. Zheng, Q. Liu, M. Han, Y. Li, M. Bao, Y. Li, 71 Y. Shen, G. Yang, W. Huang, A. Shaginian, Q. Lin, J. Wan,
P. Yan and Y. Liu, A photocatalytic traceless C–N bond for- J. Li, Y. Deng and G. Liu, Photoredox Deaminative
mation/cleavage strategy enabling the use of (α-chiral) alkyl Alkylation in DNA-Encoded Library Synthesis, Org. Lett.,
Published on 22 November 2024. Downloaded by Kyungpook National University on 10/3/2025 3:02:05 AM.

aldehydes as deoxygenative (chiral) alkyl radical equiva- 2022, 24, 2650–2654.

lents, Org. Chem. Front., 2023, 10, 5551–5558. 72 B. Wang, C.-T. Wang, X.-S. Li, X.-Y. Liu and Y.-M. Liang,
64 Y. Z. Chen, Y. M. Chen, Y. Hu, J. P. Qu and Y. B. Kang, Visible-Light-Induced C-F and C-N Bond Cleavage for the
Transalkylation via C-N Bond Cleavage of Amines Catalyzed Synthesis of gem-Difluoroalkenes, Org. Lett., 2022, 24,
by Super Organophotoreductant CBZ6, Org. Lett., 2023, 25, 6566–6560.
7518–7522. 73 G. Zhang, L. Wang, L. Cui, P. Gao and F. Chen,
65 K. Aida, M. Hirao, T. Saitoh, T. Yamamoto, Y. Einaga, Deaminative defluoroalkylation of α-trifluoromethylalkenes
E. Ota and J. Yamaguchi, Selective C–N Bond Cleavage in enabled by photoredox catalysis, Org. Biomol. Chem., 2023,
Unstrained Pyrrolidines Enabled by Lewis Acid and 21, 294–299.
Photoredox Catalysis, J. Am. Chem. Soc., 2024, 146, 30698– 74 I. Quiros, M. Martin, M. Gomez-Mendoza, M. J. Cabrera-
30707. Afonso, M. Liras, I. Fernandez, L. Novoa and M. Tortosa,
66 D. Alpers, K. P. Cole and C. R. J. Stephenson, Visible Light Isonitriles as Alkyl Radical Precursors in Visible Light
Mediated Aryl Migration by Homolytic C-N Cleavage of Aryl Mediated Hydro- and Deuterodeamination Reactions,
Amines, Angew. Chem., Int. Ed., 2018, 57, 12167–12170. Angew. Chem., Int. Ed., 2024, 63, e202317683.
67 M. A. Ashley and T. Rovis, Photoredox-Catalyzed 75 K. Liang, X. Li, D. Wei, C. Jin, C. Liu and C. Xia,
Deaminative Alkylation via C-N Bond Activation of Primary Deprotection of benzyl-derived groups via photochemically
Amines, J. Am. Chem. Soc., 2020, 142, 18310–18316. mesolytic cleavage of C–N and C–O bonds, Chem, 2023, 9,
68 J. R. Dorsheimer, M. A. Ashley and T. Rovis, Dual Nickel/ 511–522.
Photoredox-Catalyzed Deaminative Cross-Coupling of 76 K. A. Steiniger, M. C. Lamb and T. H. Lambert, Cross-
Sterically Hindered Primary Amines, J. Am. Chem. Soc., Coupling of Amines via Photocatalytic Denitrogenation of
2021, 143, 19294–19299. In Situ Generated Diazenes, J. Am. Chem. Soc., 2023, 145,
69 A. D. Marchese, J. R. Dorsheimer and T. Rovis, Photoredox- 11524–11529.
Catalyzed Generation of Tertiary Anions from Primary 77 R. Li, R. Zhan, Y. Lang, C.-J. Li and H. Zeng, Intermolecular
Amines via a Radical Polar Crossover, Angew. Chem., Int. C−C/C−N σ-bond metathesis enabled by visible light,
Ed., 2024, 63, e202317563. Chem. Sci., 2024, 15, 12900–12905.

1000 | Org. Chem. Front., 2025, 12, 975–1000 This journal is © the Partner Organisations 2025