trans-1,3-dithiane-1,3-dioxide; a chiral acyl anion equivalent. Enantioselective synthesis of α-hydroxy- carboxylic acids, esters, amides and ketones

Article abstract of DOI:10.1016/S0040-4020(97)01010-7

The reaction of (R,R)-(+)-1,3-dithiane-1,3-dioxide with aldehydes has been carried out and the dithiane dioxide moiety elaborated further. (R,R)-(+)-1,3-Dithiane-1,3-dioxide gave highly diastereoselective addition products with benzaldehyde and 3,4- dimethoxybenzaldehyde and single diastereomers were isolated in 84 and 76% purified yields respectively. Under similar conditions cyclohexane carboxaldehyde gave an easily separable mixture of diastereomers in 86% total isolated yield. The adducts were transformed into protected S- ethyl α-hydroxythioesters in 95-100% ee via a Pummerer reaction and subsequent trans-thioesterification protocol using LiSEt. Using LiSEt little racemisation occurred even with aryl substituted thioesters. Further transformations of thioesters to various α-hydroxy carboxylic acid derivatives (acids, esters, amides) without racemisation have been achieved. The approach resulted in the synthesis of the dimethyl ether of (R)-(-)-3,4-dihydroxymandelic acid in its naturally occurring form. Addition of dibutyl cuprate (derived from BuMgBr and Cu(I)Br) to the thioester gave the corresponding ketone in high yield and again without racemisation.