A General Photoredox Platform for Divergent Couplings of Alkenes with Aliphatic Carbonyls via Ligated Boryl Radicals

The
activation of aliphatic carbonyls to form ketyl radicals for
C–C bond construction remains a formidable challenge, primarily
due to their highly negative reduction potentials. Conventional strategies
typically rely on stoichiometric metal reductants or strongly reducing
conditions. Herein, we disclose a general photoredox platform that
leverages ligated boryl radicals to efficiently activate aliphatic
carbonyls, thus enabling divergent hydroxyalkylation of alkenes under
metal-free and mild conditions. Notably, this strategy accommodates
a wide range of alkenes, including α-trifluoromethyl olefins,
aliphatic olefins, heteroatom-substituted alkenes, styrenes, and electron-deficient
alkenes. Furthermore, by fine-tuning the catalytic system, the coupling
of α-CF3 alkenes with aliphatic carbonyls can be
selectively directed toward either defluoroalkylation or hydroalkylation
products with high chemoselectivity, highlighting the versatility
and tunability of this approach. Mechanistic studies confirm the critical
involvement of ligated boryl radicals in the carbonyl activation.
The synthetic utility of this protocol is further demonstrated through
late-stage functionalization of pharmaceutically relevant molecules.
With its broad substrate scope, good functional group compatibility,
and programmable selectivity, this method provides a general and practical
strategy for functionalization of aliphatic carbonyls.