Transfer C–H borylation of alkenes under Rh(I) catalysis: Insight into the synthetic capacity, mechanism, and selectivity control
Lukas Veth, Hanusch A. Grab, Sebastián Martínez, Cyril Antheaume, Paweł Dydio
Abstract
Transfer C–H borylation of alkenes bears the potential to unlock a range of attractive transformations for modular synthesis and late-stage derivatization of complex molecules. However, its scarce precedence and a limited mechanistic understanding hinders the development of practical synthetic protocols. Here, we report a Rh(I)-catalyzed transfer C–H borylation that is applicable to various terminal and internal alkenes and compatible with a plethora of functional groups, including often problematic motifs. The successful late-stage borylation of bioactive molecules, including derivatives of macrocyclic zearalenol and the drug brompheniramine, underscores its synthetic capacity. A thorough mechanistic investigation involving a series of catalytic and stoichiometric experiments as well as computational studies gave insight into the full catalytic cycle employing a β-boryl elimination, which is unprecedented for Rh-catalysis, and elucidated the features controlling the activity and the selectivity. This work sets the stage for the development of other hydrogen-for-functional group exchange reactions undergoing similar pathways.