Synthetic access to optically active isoflavans by using allylic substitution

A general approach to the (S)- and (R)-isoflavans was invented, and efficiency of the method was demonstrated by the synthesis of (S)-equol ((S)-3), (R)-sativan ((R)-4), and (R)-vestitol ((R)-5). The key step is the allylic substitution of (S)-6a (Ar-1=2,4-(MeO)(2)C6H3) and (R)-6b (Ar-1=2,4-(BnO)(2)C6H3) with copper reagents derived from CuBr center dot Me2S and Ar-2-MgBr(7a, Ar-2=4-MeOC6H4; 7b, 2,4-(MeO)(2)CrH3; 7c, 2-MOMO-4-MeOC6H3), furnishing anti S(N)2' products (R)-8a and (S)-8b,c with 93-97% chirality transfer in 60-75% yields. The olefinic part of the products was oxidativeiy cleaved and the Me and Bn groups on the Art moieties was then removed. Finally, phenol bromide 9a and phenol alcohols 9b,c underwent cyclization with K2CO3 and the Mitstmobu reagent to afford (S)-3 and (R)-4 and -5, respectively. (C) 2009 Elsevier Ltd. All rights reserved.