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Synfacts 2022; 18(12): 1355
DOI: 10.1055/s-0042-1753091
Organo- and Biocatalysis

Ene-Reductase Permits Cross-Electrophile Coupling of α-Chloro Carbonyls with α-Aryl Nitroalkanes

Contributor(s):
Benjamin List
,
Margareta M. Poje
Fu H, Cao J, Qiao T, Qi Y, Charnock SJ, Garfinkle S, Hyster TK. * Cornell University, Ithaca, USA
An Asymmetric sp 3–sp 3 Cross-Electrophile Coupling Using ‘Ene’-Reductases.

Nature 2022;
610: 302-307
DOI: 10.1038/s41586-022-05167-1.
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Key words

biocatalysis - photocatalysis - cross-electrophile coupling - ene-reductases

Significance

Hyster and co-workers describe a cross-electrophile coupling (XEC) between α-aryl nitroalkanes and α-chloro carbonyl compounds catalyzed by a flavin-dependent ene-reductase from Caulobacter segnis (CsER). Unnatural reactivity of the enzyme permits the formation of a new C–C bond through an unprecedented mechanistic pathway. The resulting β-(hetero)aryl carbonyl compounds are obtained in modest to excellent yields with poor to excellent enantioselectivities.


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Comment

Mechanistic investigations showed that a charge-transfer complex between flavin hydroquinone and the α-chloro carbonyl substrate favors the reduction of the less oxidizing coupling partner. In contrast, conventional transition-metal-based XEC strategies afford dimerized byproducts due to the inability of organometallic catalysts to differentiate between two C(sp3) electrophiles. The reported approach underlines the potential of exploiting the unique selectivity of enzymes in challenging radical-based C–C bond-forming transformations.


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Publication History

Article published online:
17 November 2022

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