SmI(2)-Mediated Radical Cross-Couplings of alpha-Hydroxylated Aza-hemiacetals and N,S-Acetals with alpha,beta-Unsaturated Compounds: Asymmetric Synthesis of (+)-Hyacinthacine A(2), (-)-Uniflorine A, and (+)-7-epi-Casuarine

Abstract

The SmI(2)-mediated radical coupling reactions of beta-hydroxylated pyrrolidine/piperidine aza-hemiacetals 8 and 9 and N,S-acetals 6 and 33 with alpha/beta-unsaturated compounds are described. This method allows a rapid access to beta-hydroxylated pyrrolidines, piperidines, pyrrolizidinones, and indolizidinones. Starting from N,S-acetal 33 and via a common intermediate 27, the alkaloids hyacinthacine A(2) (2), uniflorine A (3, 6-epi-casuarine), and the unnatural epimer 7-epi-casuarine (37) have been synthesized in four and five steps with overall yields of 34%, 16%, and 13%, respectively. The radical mechanism of the coupling reactions has been confirmed by controlled experiments, which also allowed deducing the anionic mechanism in the coupling between N,S-acetal 6 and carbonyl compounds. This demonstrates that the mechanisms of these SmI(2)-mediated reactions are switchable from Barbier-type anionic to radical by cooperative action of BF(3)center dot OEt(2) and t-BuOH.