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
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.
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.
