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Synthesis of (-) - Caryophyllene

The document discusses an unconventional approach to the enantioselective synthesis of caryophylloids, specifically (–)-b-caryophyllene and coraxenolide A, utilizing planar chirality. The synthesis involves various chemical reactions, including CBS reduction and Grob fragmentation, to achieve high yields and stereoselectivity. The significance lies in the stable planar chiral intermediate that allows for the preparation of enantiomers without racemization at room temperature.

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78 views1 page

Synthesis of (-) - Caryophyllene

The document discusses an unconventional approach to the enantioselective synthesis of caryophylloids, specifically (–)-b-caryophyllene and coraxenolide A, utilizing planar chirality. The synthesis involves various chemical reactions, including CBS reduction and Grob fragmentation, to achieve high yields and stereoselectivity. The significance lies in the stable planar chiral intermediate that allows for the preparation of enantiomers without racemization at room temperature.

Uploaded by

trancatquanpct
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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O . V. L A R I O N O V , E . J .

C O R E Y * ( H A R V A R D U N I V E R S I T Y, C A M B R I D G E , U S A ) C a te go r y

An Unconventional Approach to the Enantioselective Synthesis of Caryophylloids Synthesis of Natural


J. Am. Chem. Soc. 2008, 130, 2954-2955. Products and
Potential Drugs

Synthesis of (–)-b-Caryophyllene K e y w ord s

caryophyllene

planar chirality
O O O
NaBH4 1. DEAD, PPh3, THF, r.t. CBS reduction

AcOH, –10 °C 2. TMS-Im, TBAF (10 mol%) Grob fragmentation


O HO
OH 86%, dr = 15:1 OH THF, r.t. OTMS
61%
A B C

month
from Hajos–Parrish Ph Ph
of the
reaction
D (10 mol%)
Corey–Bakshi–Shibata reduction O BH3⋅SMe2

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
N
B THF, 0 °C
D Bu

H OTs
OTs OH

NaH 1. Et3N⋅3HF, THF, r.t.

DMF 2. TsCl, py, r.t.


r.t. to 0 °C OH 46% from C OTMS
O O– 93%
H G F E
Grob fragmentation

OTMS
I, Ph3C+ClO4– (10 mol%), CH2Cl2, –78 °C
OMe then DIBAL, –78 °C; then Et3N⋅3HF, r.t.
I 84%

O–
H H H H
1. TsCl, py, r.t. Ph3P=CH2
HO
2. t-BuOK H THF, r.t.
O i-PrOH–t-BuOH H 79% H
0 °C TsO
60% O
J K L (–)-β-caryophyllene
11 steps, 12% from A

Significance: The synthesis of b-caryophyllene Comment: The absence of stereoselectivity in the


and coraxenolide A by Larionov and Corey is dis- reduction of C with NaBH4 was overcome by us-
tinctive because it is a rare example of the use of ing the CBS reduction. Planar chiral H was ob-
planar chirality in natural product synthesis. Both tained as a single enantiomer that is stable against
enantiomers of (2Z,6E)-6-methylcyclonona-2,6- racemization at room temperature owing to re-
dienone (H) were prepared and used as chiral pre- stricted C–C bond rotation in the 9-membered
cursors for the synthesis of the (–)-b-caryophyl- ring. By contrast, cyclononene racemizes in a few
lene and coraxeniolide A. minutes at room temperature.

SYNFACTS Contributors: Philip Kocienski, Arndt W. Schmidt


Synfacts 2008, 8, 0783-0783 Publishedonline:01.08.20 8 Published online: 23.07.2008
DOI: 10.1055/s-2008-1077896; Reg-No.: K07708SF © Georg Thieme Verlag Stuttgart · New York

2008 © THIEME STUTTGART • NEW YORK 783

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