Red Light-Mediated Photoredox Catalysis Promotes Regioselective Switch in the Difunctionalization of Alkenes

Abstract

Controlling regioselectivity during difunctionalization of alkenes represents significant challenges, particularly when the installation of both functional groups is involved in radical processes. In this aspect, several functionalized trifluoromethylated (-CF3) compounds have been accomplished via difunctionalization reactions due to their wide importance in the pharmaceutical sectors, however, all these existing reports are limited to afford the corresponding β-trifluoromethylated products. The main reason for this limitation arises from the fact that -CF3 group served as an initiator in those reactions and predominantly preferred to be installed at the terminal (β) position of an alkene. In contrary, functionalization of the -CF3 group at the internal (α) position of alkenes provides valuable products but a meticulous approach is necessary to win this regioselectivity switch. Intrigued by this challenge, we have developed an efficient and highly regioselective strategy where -CF3 group is installed at the α-position of an alkene and at the end, molecular complexity is achieved via the simultaneous insertion of a sulfonyl fragment (-SO2R) at the β-position. This strategy provides the simultane-ous installation of two important functional groups such as -CF3 and -SO2R groups and both of these functional groups are the key units to attain or to enhance the bioactivity in organic molecules. A precisely regu-lated 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 dis-tinctive regioselectivity, broad substrate scope and industrial potential for the synthesis of pharmaceuticals under mild reaction conditions.