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Publication Abstract from PubMed

The catalytic asymmetric construction of Csp(3)-Csp(3) bonds remains one of the foremost challenges in organic synthesis.(1) Metal-catalyzed cross-electrophile couplings (XEC) have emerged as a powerful tool for C-C bond formation.(2-5) However, coupling two distinct Csp(3)-electrophiles with high cross- and stereoselectivity continues as an unmet challenge. Here, we report a highly chemo- and enantioselective Csp(3)-Csp(3) XEC between alkyl halides and nitroalkanes catalyzed by flavin-dependent 'ene'-reductases. Photoexcitation of the enzyme-templated charge-transfer complex between an alkyl halide and flavin cofactor enables the chemoselective reduction of alkyl halide over the thermodynamically favored nitroalkane partner. The key C-C bond-forming step occurs via the reaction of an alkyl radical with an in situ generated nitronate to form a nitro radical anion that collapses to form nitrite and an alkyl radical. An enzyme-controlled hydrogen atom transfer affords high levels of enantioselectivity. This reactivity is unknown in small molecule catalysis and highlights the potential for enzymes to use new mechanisms to address long-standing synthetic challenges.

An Asymmetric sp(3)-sp(3) Cross-Electrophile Coupling Using 'Ene'-Reductases.,Fu H, Cao J, Qiao T, Qi Y, Charnock SJ, Garfinkle S, Hyster TK Nature. 2022 Aug 11. pii: 10.1038/s41586-022-05167-1. doi:, 10.1038/s41586-022-05167-1. PMID:35952713^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.