Luca Salvi - Highly Enantio- and Diastereoselective One-pot Methods for the Synthesis of Halocyclopropyl Alcohols

Document created by Luca Salvi on Aug 22, 2014
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  Publication Details (including relevant citation   information):

  J.   Am. Chem.   Soc. 2009,   131, 954-962


  The lack of methods for the stereoselective transfer of   functionalized carbenoids is one of the most significant   deficiencies of Simmons−Smith cyclopropanation reactions.   Outlined herein are one-pot methods for the catalytic asymmetric   synthesis of halocyclopropyl alcohols with up to four stereogenic   centers from achiral starting materials. The first method   involves asymmetric alkyl addition to a conjugated enal to   generate an allylic alkoxide followed by tandem   diastereoselective iodo-, bromo-, or chlorocyclopropanation to   furnish halocyclopropyl alcohols. Enantioselectivities in these   processes range from 89−99%, and dr’s of >20:1 were achieved   with all substrates optimized. The second method consists of an   asymmetric vinylation of a saturated or aromatic aldehyde   followed by a diastereoselective iodocyclopropanation to produce   iodocyclopropyl alcohols with enantioselectivities between 86 and   99% and dr’s of >20:1. These complementary methods enable the   efficient synthesis of a variety of halocyclopropyl alcohols in   one-pot procedures. Preliminary efforts to functionalize   iodocyclopropanes involve reaction with an excess of   LiCu(n-Bu)2 to generate the cyclopropyl   cuprate. This intermediate can be quenched with allyl bromides to   generate the allylated cyclopropyl alcohols without loss of   enantio- or diastereoselectivity.

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