Pd(0)-catalyzed arylation of O-carbamates via Negishi cross-coupling and intermolecular Pd(0)-catalyzed atroposelective Csp2-H bond activation

Over the past decades, the transition-metal catalyzed C-H bond functionalization has emerged as a powerful tool for the straightforward access to molecular complexity, while respecting the principles of atom- and step-economy.
The research at the Baudoin group mainly focuses on the activation and the functionalization of C-H bonds with palladium. The investigation led to the development of new methodologies including intramolecular Csp3-H bond activation, and the arylation of remote Csp3-H bond via migrative cross-couplings. These methodologies were applied in the synthesis of biologically active complex molecules.
The ligand-controlled regioselective arylation of cyclic and acyclic N-Boc-amines via Pd(0)-catalyzed migrative Negishi cross-coupling was recently developed within our group. In light of this work, the enantioselective a-arylation of O-carbamates was achieved by combining Hoppe’s sparteine-mediated enantioselective lithiation-deprotonation and Pd(0)-catalyzed Negishi cross-coupling.
We then focused on the ligand-controlled migrative arylation of O-carbamates. The attempts toward the selective b-arylation were unsuccessful but led us to the discovery of a ligand-controlled g-arylation of g,d-unsatured O-carbamates. The reaction proceeds via a non-canonical haptotropic rearrangement of the palladium intermediate.
As a follow-up, we examined the feasibility of an intermolecular Pd(0)-catalyzed atroposelective Csp2-H arylation. Our investigation led us to the discovery of a catalytic system involving newly introduced bifunctionnal ligands.