AN IN-SITU PROCEDURE FOR CATALYTIC, ENANTIOSELECTIVE ACETATE ALDOL ADDITION - APPLICATION TO THE SYNTHESIS OF (R)-(-)-EPINEPHRINE

We report an in situ preparation of catalyst 3 which substantially sim plifies the experimental procedure for the enantioselective, catalytic acetate aldol addition reaction. The addition of Me(3)SiCl and Et(3)N circumvents the azeotropic removal of the released isopropanol upon t reating ligands 1 and 2 with Ti((OPr)-Pr-i)(4). importantly, this new procedure maintains the salient features of the catalytic process we o riginally described: high yields and enantioselectivities, low catalys t loads, and convenient reaction times and temperatures. We have appli ed the new procedure to an efficient synthesis of (R)-(-)-epinephrine from commercially available reagents in an overall yield of 45%. (C) 1 997, Elsevier Science Ltd.