Catalytic Migrative Cross-Couplings – MigraCat

The functionalization of unactivated C(sp3)-H bonds, which bears a high synthetic potential, is a major challenge of modern metal catalysis. The purpose of this project is the development of migrative Pd-catalyzed cross-couplings as a new selective C(sp3)-H functionalization strategy. The principle consists of controlling the functionalization site on an alkyl chain by favoring palladium migration with suitable ligands. In particular, we will focus on migrative couplings of functionalized organozinc reagents, generated in two different ways: from derivatives of aliphatic alcohols via a-lithiation/transmetalation (task 1) and from secondary alkyl bromides by zinc insertion (task 2). In order to streamline the development of new synthetic methodologies, the reaction kinetics will be studied upstream by in situ infrared spectroscopy, and the design of ligands and substrates controlling the coupling selectivity will be guided by DFT calculations, in a collaborative manner between both partner teams. The scope of the methods will then be studied and applications to the synthesis of enantiopure organic intermediates will be proposed.