Enantioselective hydrogenation of diaryl-substituted α,β-unsaturated nitriles

α,β-Unsaturated nitriles can be hydrogenated with enantioselectivities up to 88% ee using chiral ruthenium-diphenylphosphino bisaryl and bisheteroaryl complexes such as ruthenium(II)-BINAP and ruthenium(II)-BINP. Mechanistic investigations indicate that conversion is accelerated by electron-rich ligands and that an additional coordinative group needs be present in order to promote conversion. The chiral products are useful building blocks for the synthesis of histamine H2 agonists of the arpromidine type.

Graphical abstractDiaryl-substituted α,β-unsaturated nitriles can be hydrogenated with Ru(II)-diphosphine catalysts in up to 88% ee. Electron-rich diphosphine ligands such as N-Me-2-BINP give the best results. Mechanistic investigations show that the presence of a secondary coordination site such as a pyridyl group promotes conversion. The products are precursors for the synthesis of chiral arpromidines.Download full-size image