Ruthenium-catalyzed aldol and Michael reactions of nitriles. Carbon-carbon bond formation by α-C-H activation of nitriles

Article abstract of DOI:10.1021/ja00155a008

The ruthenium(II)-catalyzed reaction of nitriles with carbonyl compounds proceeds highly efficiently under neutral and mild conditions to give α,β-unsaturated nitriles. Under similar reaction conditions, nitriles react with olefins bearing electron-withdrawing groups to give the corresponding Michael adducts. The efficiency of the reaction is illustrated by the selective additions to α,β-unsaturated aldehydes and acetylenes bearing electron-withdrawing groups, which are difficult to perform using conventional bases. Chemoselective aldol and Michael reactions of nitriles can be performed in the presence of other active methylene compounds. Tandem Michael and Michael-aldol condensations of nitriles 30 can be performed with high diastereoselectivity. These reactions can be rationalized by assuming oxidative addition of ruthenium(0) to the α-C-H bond of nitriles and subsequent insertions to carbonyl compounds or olefins. As the key intermediates and active catalysts hydrido(N-bonded enolato)ruthenium(II) complexes, mer-RuH(NCCHCO₂R)(NCCH₂CO₂R)(PPh₃)₃ (R = Me (41a), Et (41b), n-Bu (41c)) have been isolated upon treatment of RuH₂(PPh₃)₄ (3) or RuH(C₂H₄)(PPh₃)₂(PPh₂C₆H₄) (4) with alkyl cyanoacetates. Kinetic study of the catalytic aldol reaction of ethyl cyanoacetate with benzaldehyde indicates that the rate-determining step is the reaction of enolato complex 41 with aldehydes.