Synthesis of ( R)- and ( S)-4-hydroxyisophorone by ruthenium-catalyzed asymmetric transfer hydrogenation of ketoisophorone

Abstract

The first synthesis of ( R)- and ( S)-4-hydroxyisophorone by catalytic transfer hydrogenation of ketoisophorone is reported. Ruthenium catalysts containing commercially available chiral amino alcohols afforded 4-hydroxyisophorone in up to 97% selectivity and 97% ee. ( R)- or ( S)-4-Hydroxyisophorones with >99% ee were isolated by crystallization. The catalyst precursors [RuCl 2(( S, R)-ADPE)(η 6- p-cymene)] (( S, R)-ADPE=(1 S,2 R)-amino-1,2-diphenylethanol- N) and ( R Ru)-[RuCl(( S, R)-ADPE −1)(η 6- p-cymene)] (ADPE −1=amino-1,2-diphenylethanolato- N, O) were isolated for the first time and the X-ray crystal structure of the latter determined.