Catalytic Asymmetric Synthesis of Fluoroalkyl-Containing Compounds by Three-Component Photoredox Chemistry.

Abstract

Multicomponent reactions allow the construction of molecular complexity in an economical fashion, fluorinated compounds play an important role in pharmaceuticals and agrochemicals, whereas visible light is an abundant and sustainable source of energy for activating chemical transformations. Here we report a visible-light-induced asymmetric three-component fluoroalkylation reaction scheme catalyzed by a chiral-at-rhodium Lewis acid. The photoredox process is mediated by the inexpensive, commercially available organic photoredox mediator 4,4'-difluorobenzil, which upon activation by visible light induces the generation of perfluoroalkyl radicals from their sulfinates via single electron transfer oxidation. The fluorinated radicals are trapped by electron-rich C-C double bonds to deliver α-oxy carbon-centered radicals, followed by a subsequent stereocontrolled reaction with acceptor-substituted alkenes. This three-component fluoroalkylation scheme provides a range of complex fluoroalkyl-containing chiral compounds under dual C-C bond formation with high enantioselectivities (up to 98 % ee) and modest diastereoselectivities (up to 6:1 dr). Excellent diastereoselectivities (up to >38:1:1 dr) for natural chiral compound derivatives are observed. Broad substrate scope (25 examples), excellent functional group tolerance, scalability of the reaction, along with the option to recover the chiral catalyst and photoredox mediator reveal the practicability of this methodology in organic synthesis for the rapid synthesis of fluorinated chiral molecules.