Highly stereoselective oxy-Michael additions to α,β-disubstituted nitroolefins: asymmetric synthesis of pseudo-norephedrine derivatives and THP* protected α-hydroxy ketones

Abstract

The “naked” anion of (S)-6-methyl delta lactol undergoes efficient oxy-Michael addition to α,β-disubstituted nitro olefins to give the THP* protected Henry products with excellent (95→98% de) stereocontrol at the β-position and moderate (up to 3 : 1) stereocontrol at the α-position in favour of the syn-diastereoisomer. Nitro group reduction with in situN-Boc protection and THP* removal provides α,β-disubstituted ethanolamine derivatives, while treatment with tetrapropylammonium perruthenate gives THP* protected α-hydroxy ketone derivatives in high diasteromeric excess.