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)(PPh 3 ) 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 C sp 2 –C sp 3 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.