Enantioselective construction of bicyclo[3.1.0]hexane derivatives through asymmetric deprotonation of meso-cyclic ketones

Abstract

An efficient asymmetric synthesis of bicyclo[3.1.0]hexane derivatives was achieved. The three-step conversion of 6-hydroxytricyclo[3.2.1.0 2,7]octan-3-one 2, (derived from 3-oxatricyclo[3.3.1.0 2,4]nonan-7-one 1 through an asymmetric deprotonation reaction) led to 6 in optically active form. Alternatively, the asymmetric deprotonation reaction of meso-cyclic ketones 9a and 9b with several chiral lithium amide bases was examined to give silyl enol ether 12 and triflate 21 with high enantioselectivity. The absolute configuration of the triflate 21 was determined by investigation of the chemical relationship between 21 and 6.