Red-light-mediated copper-catalyzed photoredox catalysis promotes regioselectivity switch in the difunctionalization of alkenes

Controlling regioselectivity during difunctionalization of alkenes remains a significant challenge, particularly when the installation of both functional groups involves radical processes. In this aspect, methodologies to install trifluoromethane (−CF 3 ) via difunctionalization have been explored, due to the importance of this moiety in the pharmaceutical sectors; however, these existing reports are limited, most of which affording only the corresponding β-trifluoromethylated products. The main reason for this limitation arises from the fact that −CF 3 group served as an initiator in those reactions and predominantly preferred to be installed at the terminal (β) position of an alkene. On the contrary, functionalization of the −CF 3 group at the internal (α) position of alkenes would provide valuable products, but a meticulous approach is necessary to win this regioselectivity switch. Intrigued by this challenge, we here develop an efficient and regioselective strategy where the −CF 3 group is installed at the α-position of an alkene. Molecular complexity is achieved via the simultaneous insertion of a sulfonyl fragment (−SO 2 R) at the β-position. A precisely regulated sequence of radical generation using red light-mediated photocatalysis facilitates this regioselective switch from the terminal (β) position to the internal (α) position. Furthermore, this approach demonstrates broad substrate scope and industrial potential for the synthesis of pharmaceuticals under mild reaction conditions. Many photocatalytic synthetic organic methodologies proceed through radical intermediates, which lead to generally predictable alkene functionalization patterns. Here the authors install a useful trifluoromethyl group at the unusual alpha position via red-light copper photocatalysis.