Synthesis, enzymic resolution and enantiomeric enhancement of bis(hydroxymethyl)[7]thiaheterohelicenes

Abstract

Racemic bis(hydroxymethyl)[7]thiaheterohelicene 9 has been prepared in eight steps (33% overall yield) from 2-(hydroxymethyl)benzo[1,2-b:4,3-b′]dithiophene 1. Lipase (Pseudomonas cepacia)-catalyzed transesterification of diol 9 by vinyl acetate in dichloromethane produces optically stable (P)-bis(hydroxymethyl)[7]thiaheterohelicene [(P)-9] with 98% ee along with the corresponding monoacetate [(M)-10] and the diacetate [(M)-11]. Hydrolysis of acetates (M)-10 and (M)-11 by aq. NaOH gives (M)-9 in 77% and 94% ee, respectively. In contrast, the enzymic resolution of diol 9 with Candida antarctica afforded diol (M)-9 in 92% ee. Column chromatography of optically enriched helicenediol 9 on silica gel shows an enantiomeric enhancement. A possible cause of the phenomenon is discussed.