Chiral Lewis Base Catalyzed Enantioselective Acetylcyanation of α‐Oxo Esters

Acetyl cyanide adds to alkyl benzoylformates and to 2‐oxoalkanoates to yield enantioenriched acylated cyanohydrins in one step in the presence of a catalytic amount of a chiral base. The reaction is accelerated by Lewis acids and by the addition of a catalytic amount of methanol. Under optimized conditions, 94 % of a 94:6 mixture of the O‐acetylated and non‐protected cyanohydrins was formed from methyl benzoylformate in the presence of cinchonidine; from this mixture the acylated compound with 66 % ee was isolated in 77 % yield. Ethyl pyruvate and tert‐butyl 2‐oxobutanoate were more reactive, and essentially full conversion to the products with 69 and 82 % ee, respectively, was achieved. The reaction proceeds by a non‐selective addition of cyanide ion to give the non‐protected cyanohydrin followed by a dynamic kinetic resolution to provide the enantioenriched acetylated product. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) Acetyl cyanide adds to activated ketones to give enantioenriched O‐acylated cyanohydrins in the presence of a chiral base.