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Flavin‐dependent ‘ene’‐reductases (EREDs) are highly selective catalysts for the asymmetric reduction of activated alkenes. This function is, however, limited to enones, enoates, and nitroalkenes using the native hydride transfer mechanism. Here we demonstrate that EREDs can reduce vinyl pyridines when irradiated with visible light in the presence of a photoredox catalyst. Experimental evidence suggests the reaction proceeds via a radical mechanism where the vinyl pyridine is reduced to the corresponding neutral benzylic radical in solution. DFT calculations reveal this radical to be “dynamically stable”, suggesting it is sufficiently long lived to diffuse into the enzyme active site for stereoselective hydrogen atom transfer. This reduction mechanism is distinct from the native one, highlighting the opportunity to expand the synthetic capabilities of existing enzyme platforms by exploiting new mechanistic paradigms.

The catalytic umpolung of imines remains an underdeveloped approach to reaction discovery. Herein we report an enantioselective aza-Stetter reaction that proceeds via imine umpolung using N-heterocyclic carbene catalysis. The reaction proceeds with high levels of enantioselectivity (all ≥96:4 er) and good generality (21 examples). Mechanistic studies are reported and are consistent with turnover-limiting addition of the NHC to the imine.

Herein we report the cycloisomerization of electron-poor 1,5-dienes via the β-azolium ylide to give enantioenriched cyclopentenes. The reaction is mediated by a chiral N-heterocyclic carbene (NHC) catalyst, exploits readily available substrates, has good generality (17 examples), and displays excellent enantioselectivity (mostly >94:6). Studies demonstrating the viability of a related dynamic kinetic resolution are reported, as are those with alternate tethers and derivatizations.

N-Heterocyclic carbene-catalyzed formation of β-anionic intermediates from enones has been employed in the enantioselective synthesis of 2-aryl propionates. The reaction was achievable using a homochiral 4-MeOC6H4 morpholinone catalyst allowing the first example of enantioselective catalysis by umpolung of α,β-unsaturated ketones. The reaction is high yielding, and shows robustness with reasonable generality. A mechanism is proposed in which the enantiodetermining protonation is achieved using either hexafluoroisopropanol or the formed naphthol product.