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

Research paper by Jiajia J Ma, Xiulan X Xie, Eric E Meggers

Indexed on: 07 Nov '17Published on: 07 Nov '17Published in: Chemistry - A European Journal



Abstract

Here we report a visible-light-induced asymmetric three-component fluoroalkylation reaction scheme catalyzed by a stereogenic-at-metal rhodium-based 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 respective sulfinates via single electron transfer (SET) oxidation. The fluorinated radicals are subsequently trapped by electron-rich C-C double bonds to deliver α-oxyl carbon-centered radical species, followed by a 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.