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 C_sp²–C_sp³ 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.