Premium
Chiral Lewis Base Catalyzed Enantioselective Acetylcyanation of α‐Oxo Esters
Author(s) -
Li Fei,
Widyan Khalid,
Wingstrand Erica,
Moberg Christina
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200900055
Subject(s) - chemistry , cyanohydrin , kinetic resolution , enantioselective synthesis , catalysis , yield (engineering) , lewis acids and bases , organic chemistry , methanol , hydrolysis , cinchonidine , cyanide , medicinal chemistry , materials science , metallurgy
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)