Luca Salvi - One-Pot Catalytic Enantio- and Diastereoselective Syntheses of anti-, syn-cis-Disubstituted, and syn-Vinyl Cyclopropyl Alcohols

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      Publication Details (including relevant citation   information):

      J. Am.   Chem. Soc. 2010,   132, 402-412

      Abstract:

      Highly enantio- and diastereoselective methods for the synthesis   of a variety of cyclopropyl alcohols are reported. These methods   represent the first one-pot approaches to syn-vinyl   cyclopropyl alcohols, syn-cis-disubstituted   cyclopropyl alcohols, and anti-cyclopropyl alcohols from   achiral precursors. The methods begin with enantioselective C−C   bond formations promoted by a MIB-based zinc catalyst to generate   allylic alkoxide intermediates. The intermediates are then   subjected to in situ alkoxide-directed cyclopropanation to   provide cyclopropyl alcohols. In the synthesis of vinyl   cyclopropyl alcohols, hydroboration of enynes is followed by   transmetalation of the resulting dienylborane to zinc to provide   dienylzinc reagents. Enantioselective addition to aldehydes   generates the requisite dienyl zinc alkoxides, which are then   subjected to in situ cyclopropanation to furnish vinyl   cyclopropyl alcohols. Cyclopropanation occurs at the double bond   allylic to the alkoxide. Using this method,   syn-vinylcyclopropyl alcohols are obtained in 65−85%   yield, 76−93% ee, and >19:1 dr. To prepare   anti-cyclopropanols, enantioselective addition of   alkylzinc reagents to conjugated enals provides allylic zinc   alkoxides. Because direct cyclopropanation provides   syn-cyclopropyl alcohols, the intermediate allylic   alkoxides were treated with TMSCl/Et3N to generate   intermediate silyl ethers. In situ cyclopropanation of the   allylic silyl ether resulted in cyclopropanation to form the   anti-cyclopropyl silyl ether. Workup with TBAF affords   the anti-cyclopropyl alcohols in one pot in 60−82%   yield, 89−99% ee, and ≥10:1 dr. For the synthesis of   cis-disubstituted cyclopropyl alcohols, in situ   generated (Z)-vinyl zinc reagents were employed in   asymmetric addition to aldehydes to generate (Z)-allylic   zinc alkoxides. In situ cyclopropanation provides   syn-cis-disubstituted cyclopropyl alcohols in   42−70% yield, 88−97% ee, and >19:1 dr. These one-pot   procedures enable the synthesis of a diverse array of cyclopropyl   alcohol building blocks with high enantio- and   diastereoselectivities.

      Address (URL): http://pubs.acs.org/doi/abs/10.1021/ja907781t?prevSearch=%2528luca%2Bsalvi%2529% 2BNOT%2B%255Batype%253A%2Bad%255D%2BNOT%2B%255Batype%253A%2Bacs-toc%255D&searchH istoryKey=