Late-Stage C(sp 2)-C(sp 3) Diversification via Nickel Oxidative Addition Complexes

Identifier:  imarina:9378994

Handle: https://hdl.handle.net/20.500.11797/imarina9378994

Authors:  Odena, C; Santiago, TG; Linares, ML; Castellanos-Blanco, N; McGuire, RT; Chaves-Arquero, B; Alonso, JM; Diéguez-Vázquez, A; Tan, E; Alcázar, J; Buijnsters, P; Cañellas, S; Martin, R

Abstract:
Herein, we describe nickel oxidative addition complexes (Ni-OACs) of drug-like molecules as a platform to rapidly generate lead candidates with enhanced C(sp(3)) fraction. The potential of Ni-OACs to access new chemical space has been assessed not only in C(sp(2))-C(sp(3)) couplings but also in additional bond formations without recourse to specialized ligands and with improved generality when compared to Ni-catalyzed reactions. The development of an automated diversification process further illustrates the robustness of Ni-OACs, thus offering a new gateway to expedite the design-make-test-analyze (DMTA) cycle in drug discovery.