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 simplifies 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 treating ligands 1 and 2 with Ti((OPr)-Pr-i)(4). importantly, this new procedure maintains the salient features of the catalytic process we originally described: high yields and enantioselectivities, low catalyst loads, and convenient reaction times and temperatures. We have applied the new procedure to an efficient synthesis of (R)-(-)-epinephrine from commercially available reagents in an overall yield of 45%. (C) 1997, Elsevier Science Ltd.