Cyclopropanation with Dibromomethane under Grignard and Barbier Conditions

Abstract

C y c l o p r o p a n a t i o n w i t h D i b r o m o m e t h a n eAbstract: Tertiary Grignard reagents and dibromomethane efficiently cyclopropanate allylic (and certain homoallylic) magnesium and lithium alcoholates at ambient temperature in ether solvents. Lithium (homo)allyl alcoholates are directly cyclopropanated with magnesium and dibromomethane under Barbier conditions at higher temperatures. The reaction rates depend on the substitution pattern of the (homo)allylic alcoholates and on the counterion with lithium giving best results. Good to excellent syn-selectivities are obtained from a-substituted (homo)allyl alcohols. In tandem reactions, cyclopropyl carbinols are obtained from allyloxylithium or -magnesium intermediates, generated in situ by alkylation of conjugated aldehydes, ketones, and esters as well as from allyl esters and carbonates or vinyloxiranes. 1 Scheme 1 OH 1 a OH 2 a (dr = 1:1) CH 2 Br 2 (3 equiv), 10-30 °C, Et 2 O t-BuMgCl (4 equiv), THF, 87% P r o c e d u r e 1 : Deprotonation with t-BuMgCl and cyclopropanation with CH 2 Br 2 P r o c e d u r e 2 : Sequential Grignard addition / cyclopropanation of conjugated aldehydes CHO OH 5 g 2 gPentylMgBr in THF, 0 °C, then CH 2 Br 2 (3 equiv), 10-30 °C, then t-BuMgCl (3 equiv), Et 2 O, 95%