Asymmetric base-free michael addition at room temperature with nickel-based bifunctional amido-functionalized N-heterocyclic carbene catalysts

Abstract

A series of nickel-based chiral bifunctional catalysts (1d-3d) with N-heterocyclic carbene (NHC) ligands derived from (1R)-(-)-menthol, (1S)-(-)pinene, and (1R)-(+)-camphor have been successfully designed for asymmetric Michael addition reactions under base-free conditions. The NHC complexes, namely, [1-R-3-{N-(phenylacetamido)}imidazol-2-ylidene]2Ni [R = (1S)-menthyl (1d), (1S)-pinane (2d), and (1R)-isobornyl (3d)], bearing chiral ancillaries on the amido-functionalized side arms of the NHC ligands, performed the bifunctional catalysis of the asymmetric base-free Michael addition reaction of the α-methyl cyano ester substrates ethyl 2-cyanopropanoate (4), isopropyl 2-cyanopropanoate (5), and tert-butyl 2-cyanopropanoate (6) with the activated olefinic substrates methyl vinyl ketone (7) and acrylonitrile (8) in 63-98 % yields with enantiomeric excess (ee) values of 2-75 % at room temperature in 8 h. More interestingly, only the longest of the three catalysts, the menthol derivative 1d, showed significant chiral induction of up to 75 % ee; this has been attributed to the reduction of the steric influence owing to the relatively distant dispositions of the chiral ancillaries from the catalytically active metal center that arise as a consequence of the cis geometries of 1d-3d. A series of nickel-based chiral bifunctional catalysts with N-heterocyclic carbene ligands derived from readily available and inexpensive (1R)-(-)-menthol, (1S)-(-)pinene, and (1R)-(+)-camphor synthons successfully catalyze asymmetric base-free Michael addition reactions under ambient conditions.