Ruthenium-Catalyzed Conjugation of Phenyl and Pyridyl Bioisosteres to Azines/Azoles Via Dearomative Addition–Hydrogen Auto-Transfer

Using the inexpensive, air-stable ruthenium catalyst derived from RuHCl(CO)(PPh3)3 and the achiral ligands Cy-BIPHEP or dCypb, acetylenic bicyclooctyl, azabicycloheptyl, adamantyl, bicyclopentyl and azabicyclooctyl bioisosteres 2a-2f are conjugated to diverse azines and azoles 1a-1t via Csp2-Csp3 bond formation. Using chiral ruthenium catalysts modified by (S)-Cy-SEGPHOS or (R)-Cy-BINAP, high levels of enantioselectivity are obtained in reactions of azines. Late-stage C-H functionalization of the B(Epin) derivative of bortezomib (Velcade) and studies corroborating the reaction mechanism are described.