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. 2017 Mar 17;82(6):3192-3222.
doi: 10.1021/acs.joc.7b00295. Epub 2017 Mar 3.

Catalytic, Enantioselective, Intramolecular Sulfenofunctionalization of Alkenes with Phenols

Scott E Denmark  1 , David J P Kornfilt  1
Affiliations

Catalytic, Enantioselective, Intramolecular Sulfenofunctionalization of Alkenes with Phenols

Scott E Denmark et al. J Org Chem. .

Abstract

The catalytic, enantioselective, cyclization of phenols with electrophilic sulfenophthalimides onto isolated or conjugated alkenes affords 2,3-disubstituted benzopyrans and benzoxepins. The reaction is catalyzed by a BINAM-based phosphoramide Lewis base catalyst which assists in the highly enantioselective formation of a thiiranium ion intermediate. The influence of nucleophile electron density, alkene substitution pattern, tether length and Lewis base functional groups on the rate, enantio- and site-selectivity for the cyclization is investigated. The reaction is not affected by the presence of substituents on the phenol ring. In contrast, substitutions around the alkene strongly affect the reaction outcome. Sequential lengthening of the tether results in decreased reactivity, which necessitated increased temperatures for reaction to occur. Sterically bulky aryl groups on the sulfenyl moiety prevented erosion of enantiomeric composition at these elevated temperatures. Alcohols and carboxylic acids preferentially captured thiiranium ions in competition with phenolic hydroxyl groups. An improved method for the selective C(2) allylation of phenols is also described.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Chart 1
Chart 1. Chroman-Containing Therapeutic Agents
Scheme 1
Scheme 1. Retrosynthetic Disconnections for Construction of Chromans
Scheme 2
Scheme 2. Enantioselective Construction of Chromans
Scheme 3
Scheme 3. Synthesis of 2,3-Disubstituted Chromans
Scheme 4
Scheme 4. Lewis Base Catalyzed Sulfenofunctionalization of Alkenes
Figure 1
Figure 1
Catalytic cycle for the enantioselective, intramolecular sulfenylation.
Scheme 5
Scheme 5. Manipulations of 3-Phenylthiochroman
Scheme 6
Scheme 6. Influence of Tether Length and Substituents on Constitutional Site Selectivity
Scheme 7
Scheme 7. Constitutional Site Selectivity for 4-Pentenols
See this image and copyright information in PMC

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