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Catalytic asymmetric generation of (Z)-disubstituted allylic alcohols.

Authors
  • Salvi, Luca
  • Jeon, Sang-Jin
  • Fisher, Ethan L
  • Carroll, Patrick J
  • Walsh, Patrick J
Type
Published Article
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Publication Date
Dec 26, 2007
Volume
129
Issue
51
Pages
16119–16125
Identifiers
PMID: 18052173
Source
Medline
License
Unknown

Abstract

A one-pot method for the direct preparation of enantioenriched (Z)-disubstituted allylic alcohols is introduced. Hydroboration of 1-halo-1-alkynes with dicyclohexylborane, reaction with t-BuLi, and transmetalation with dialkylzinc reagents generate (Z)-disubstituted vinylzinc intermediates. In situ reaction of these reagents with aldehydes in the presence of a catalyst derived from (-)-MIB generates (Z)-disubstituted allylic alcohols. It was found that the resulting allylic alcohols were racemic, most likely due to a rapid addition reaction promoted by LiX (X = Br and Cl). To suppress the LiX-promoted reaction, a series of inhibitors were screened. It was found that 20-30 mol % tetraethylethylenediamine inhibited LiCl without inhibiting the chiral zinc-based Lewis acid. In this fashion, (Z)-disubstituted allylic alcohols were obtained with up to 98% ee. The asymmetric (Z)-vinylation could be coupled with tandem diastereoselective epoxidation reactions to provide epoxy alcohols and allylic epoxy alcohols with up to three contiguous stereogenic centers, enabling the rapid construction of complex building blocks with high levels of enantio- and diastereoselectivity.

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