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. 2010 Apr 14;132(14):4986-7.
doi: 10.1021/ja100748y.

The productive merger of iodonium salts and organocatalysis: a non-photolytic approach to the enantioselective alpha-trifluoromethylation of aldehydes

Anna E Allen  1 , David W C Macmillan
Affiliations

The productive merger of iodonium salts and organocatalysis: a non-photolytic approach to the enantioselective alpha-trifluoromethylation of aldehydes

Anna E Allen et al. J Am Chem Soc. .

Abstract

An enantioselective organocatalytic alpha-trifluoromethylation of aldehydes has been accomplished using a commercially available, electrophilic trifluoromethyl source. The merging of Lewis acid and organocatalysis provides a new strategy for the enantioselective construction of trifluoromethyl stereogenicity, an important chiral synthon for pharmaceutical, materials, and agrochemical applications. This mild and operationally simple protocol allows rapid access to enantioenriched alpha-trifluoromethylated aldehydes through a nonphotolytic pathway.

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Figures

Scheme 1
Scheme 1
Proposed Mechanism for Direct α-Trifluoromethylation
Scheme 2
Scheme 2
Access to Enantioenriched Trifluoromethyl Synthons
See this image and copyright information in PMC

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    1. Imidazolidinone 3 can be purchased from Sigma-Aldrich as the hydrochloric acid salt (CAS: 278173-23-2). The hydrochloric acid salt was converted to the trifluoroacetic acid salt before use in this protocol.

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