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Cyclization of Homoallylic Alcohols With Iodine/Iodine (III)

This document describes a method for synthesizing tetrahydrofuran compounds by cyclizing homoallylic alcohols using iodine and hypervalent iodine. The reaction proceeds through an iodonium intermediate that can undergo attack by an external methanol molecule or the internal hydroxyl group. Oxidation then forms an iodine(III) species that allows for intramolecular attack and ring closure to form the tetrahydrofuran product. This methodology was demonstrated to work for various substituted homoallylic alcohol substrates, providing the desired tetrahydrofuran products in good yields and with some stereoselectivity.

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36 views1 page

Cyclization of Homoallylic Alcohols With Iodine/Iodine (III)

This document describes a method for synthesizing tetrahydrofuran compounds by cyclizing homoallylic alcohols using iodine and hypervalent iodine. The reaction proceeds through an iodonium intermediate that can undergo attack by an external methanol molecule or the internal hydroxyl group. Oxidation then forms an iodine(III) species that allows for intramolecular attack and ring closure to form the tetrahydrofuran product. This methodology was demonstrated to work for various substituted homoallylic alcohol substrates, providing the desired tetrahydrofuran products in good yields and with some stereoselectivity.

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Paulo S. Filho
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© Attribution Non-Commercial (BY-NC)
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Cyclization of Homoallylic Alcohols with Iodine/Iodine(III)

Paulo Scarassati and Luiz F. Silva Jr.*


Instituto de Qumica, USP, CP 26077, CEP 05513-970, So Paulo SP, Brazil [email protected] and *[email protected] Keywords: Homoallylic Alcohols, Cyclization, Hypervalent Iodine, Tetrahydrofurans

INTRODUCTION
Tetrahydrofurans compounds can be obtained by cyclofunctionalization of homoallylic alcohols.1 Many electrophiles have been used, such as halogens, thallium(III), mercury(II), selenium, etc.1 The iodocyclization of homoallylic alcohols with terminal double bonds leads to the formation of oxetanes,2 because the 5-endo-trig cyclization is not favored for these substrates. The use of hypervalent iodine with a catalytic amount of molecular iodine possibilitates the formation of THFs rings from homoallylic alcohols (Scheme 1).3

Scheme 3. Preparation of starting materials 6a-d Table 1. Reaction of 6a-e with I2/HTIB Scheme 1. Iodocyclization of homoallylic alcohols The reaction of 1 initially originated two differents compounds (2a-b) that led to the desired tetrahydrofuran 5. Interrupting the reaction in the beginning, it was possible to characterize these intermediates. The proposed mechanism (Scheme 2) is divided into two routes: a) Attack of external MeOH (2a) or b) Attack of internal hydroxyl group (2b) to the iodonium intermediate. The oxidation of alkyl iodides (2a-b) by HTIB (PhI(OH)OTs) gives the corresponding I(III) species, which is a hypernucleofuge. In route a, intramolecular attack of the hydroxyl group to the I(III) moiety of 3a gives 5. In route b, the displacement of iodine group by oxygen leads the bicyclic oxonium ion 4. MeOH attacks giving 5.

a2

equiv of HTIB, 0.2 equiv of I2, MeOH, rt, overnight; b ratio between diasteromers

Figure 1. Color before and after the reaction completion

CONCLUSION
Scheme 2. Mechanism for I2/Iodine(III) cyclization This methodology can serve well for obtaining substituted tetrahydrofurans starting from primary and secundary homoallylic alcohols.

RESULTS AND DISCUSSION


6a-d were prepared as reported (Scheme 3), whereas 6e is commercially available. The reaction of the homoallylic alcohols 6a-e with HTIB and I2 led to the formation of the desired products (Table 1). The diasteromer ratio was determined by GC or NMR. No significant stereoselectivity was observed for 6a-d, but for substrate 6e, the reaction is stereospecific. The cylizations can be easily monitored by color change (Figure 1).

ACKNOWLEDGEMENTS
FAPESP, CNPq and CAPES for financial support

REFERENCES
1. Jalce, G.; Franck, X.; Figadre, B. Tetrahedron: Asymmetry 2009, 20, 2537. 2. Evans, R. D.; Magee, J. W.; Schauble, J. H. Synthesis 1988, 11, 862. 3. Vasconcelos, R. S.; Silva, L. F., Jr; Giannis, A. J. Org. Chem. 2011, 76 1499.

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