Journal of the American Chemical Society

Catalytic asymmetric aza-Morita-Baylis-Hillman reaction of methyl acrylate: role of a bifunctional La(O-iPr)3/linked-BINOL complex.

PMID 20690698


The catalytic asymmetric aza-Morita-Baylis-Hillman reaction using unactivated methyl acrylate is described. A simple Lewis acidic metal catalyst, such as La(OTf)(3), was not suitable for the reaction, but rare earth metal alkoxide/linked-BINOL complexes possessing bifunctional Lewis acid and Brønsted base properties efficiently promoted the reaction in combination with an achiral nucleophilic organocatalyst. The combined use of a La(O-iPr)(3)/(S,S)-TMS-linked-BINOL complex with a catalytic amount of DABCO promoted the aza-Morita-Baylis-Hillman reaction of a broad range of N-diphenylphosphinoyl imines. Products from aryl, heteroaryl, and alkenyl imines were obtained in 67-99% yield and 81-95% ee. It is noteworthy that isomerizable alkyl imines could be employed as well, giving products in 78-89% yield and 94-98% ee. Initial rate kinetic studies as well as kinetic isotope effect experiments using alpha-deuterio-methyl acrylate support the importance of both the nucleophilicity of La-enolate and the Brønsted basicity of a La-catalyst for promoting the reaction.