Practical synthesis of enantiopure gamma-amino alcohols by rhodium-catalyzed asymmetric hydrogenation of beta-secondary-amino ketones.

Enantioselective hydrogenation of amino ketones catalyzed by Ru– or Rh–phosphine complexes provides an efficient method for the synthesis of enantiomerically active amino alcohols, a class of chiral compounds of great importance in pharmaceutical products. A recent challenging target inspired us to look for a practical solution for the enantioselective reduction of b-amino ketones with a secondary amino group, an unsolved class of substrates in asymmetric hydrogenation. To our knowledge, no Ru catalytic system has successfully been used for the asymmetric hydrogenation of amino ketones with a secondary amino group. A Rh– MCCPM (MCCPM= (2S,4S)-4-dicyclohexylphosphino-2diphenylphosphinomethyl-1-(N-methylcarbamoyl)pyrrolidine) catalyst has been reported for the hydrogenation of one b-secondary-amino ketone substrate with only moderate efficiency (80% ee, turnover number (TON)= 1000). Given the importance of chiral g-amino alcohols 2 as key intermediates for the synthesis of pharmaceutical products 1 (Scheme 1), an efficient enantioselective reduction of b-