An in situ procedure for catalytic, enantioselective acetate aldol addition. Application to the synthesis of (R)-(-)-epinephrine

Article abstract of DOI:10.1016/S0040-4039(96)02515-4

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 Me₃SiCl and Et₃N circumvents the azeotropic removal of the released isopropanol upon treating ligands 1 and 2 with Ti(O(i)Pr)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%.