ASYMMETRIC INDUCTION IN THE THIO-CLAISEN REARRANGEMENT - CREATION OF 3 CONTIGUOUS STEREOGENIC CENTERS FROM ALPHA-HYDROXY KETENE DITHIOACETALS

Syn beta-hydroxy gamma-methyl dithioesters were deprotonated with two equivalents of LDA. A subsequent S-alkylation of the resulting dianions yielded alpha-hydroxy S-allyl ketene dithioacetals. A single isomer was observed, arising from a selective cis deprotonation. These dithioacetals underwent a rapid and highly diastereoselective thio-Claisen rearrangement at an ambient temperature. Syn-syn alpha-allyl beta-hydroxy gamma-methyl dithioesters were mainly formed. The syn-syn/anti-syn ratios ranged from 85:15 to 99:1. The selectivity observed originates from asymmetric: induction with a noteworthy stereoelectronic effect of the hydroxyl group. Configurations were assigned by a spectroscopic method using previously reported C-13 NMR rules and then confirmed by a syn-syn diastereoselective aldol reaction. This novel and efficient method for the creation of frameworks with three contiguous stereogenic centres, involves two diastereoselective steps: an aldol reaction followed by a thio-Claisen rearrangement.