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.