Palladium-Catalysed Migratory Suzuki-Miyaura Cross-Coupling

The installation of a functional group at a specific site through transition-metal catalysed C-H functionalisation has emerged as a powerful tool for the synthesis of complex structures in a step-economical manner. In this context, the remote functionalisation through migration of a transition-metal catalyst along an alkyl-chain, termed chain-walking, has gained significant momentum during the last decade.
The strategy developed by the group of Baudoin relies on palladium-catalysed ligand-controlled chain-walk with enolates or organozinc compounds as nucleophiles, where a site-selective reductive elimination is the terminating step. More recently, the group reported the development of a regioconvergent functionalisation of a regioisomeric mixture of bromoalkanes through a migratory Barbier-Negishi cross-coupling. However, the design of a migratory version of the ubiquitous Suzuki-Miyaura cross-coupling has remained elusive, although various palladium-catalysed migratory cross-coupling reactions were reported.
In this optic, we first investigated a one-pot approach for the hydroboration of a regioisomeric mixture of linear alkenes and subsequent terminal-selective palladium-catalysed Suzuki-Miyaura cross-coupling. The developed reaction conditions furnished excellent regioselectivity, but the yields were not satisfactory.
We then developed a benzylic-selective palladium-catalysed Suzuki-Miyaura cross-coupling based on the previous observations made. Excellent regioselectivity for the benzylic position of the initial alkene was achieved by the combination of ligand and electrophile. We also demonstrated the regioconvergence from regio- and geometrical isomeric mixture of alkenes, and long-range migration. Additionally, a mechanistic study was also performed.
Finally, we also explored the feasibility of combining the previous benzylic-selective migratory cross-coupling with a subsequent C(sp2)-H activation in a cascade process. However, our findings led to the conclusion that the necessary presence of water for the first step is detrimental for the second.