Highly asymmetric Pummerer-type cyclization of chiral, non-racemic β-amido sulfoxides

Abstract

The first highly asymmetric Pummerer-type cyclization of chiral, non-racemic β-amido sulfoxides to enantiomerically enriched β-lactams (80–85% ee) is described. S- and R-Sulfoxides (S-2a–d and R-2a–c) were treated with O-methyl-O-tert-butyldimethylsilyl ketene acetal 1 in the presence of a catalytic amount of zinc chloride in methylene dichloride to give predominantly the corresponding 4R- and 4S-β-lactams (R-3a–d and S-3a–c) in more than 80% ee. These results show that the stereoinduction is governed by the absolute configuration of the sulfoxides. Optically pure R- and S-3c were readily obtained by simple recrystallization in about 60% yield. The usefulness of the chiral, non-racemic 4-tolylsulfanyl-β-lactams 3a–d has been shown by their conversion into the key intermediate 11 for the optically pure carbapenem antibiotic, (+)-PS-5.