We report the exploration into photoredox generation of carbonyl ylides from benzylic epoxides using newly designed 4-mesityl-2,6-diphenylpyrylium tetrafluoroborate (MDPT) and 4-mesityl-2,6-di-p-tolylpyrylium tetrafluoroborate (MD(p-tolyl)PT) catalysts. These catalysts are excited at visible wavelengths, are highly robust, and exhibit some of the highest oxidation potentials reported. Their utility was demonstrated in the mild and efficient generation of carbonyl ylides from benzylic epoxides that otherwise could not be carried out by current common photoredox catalysts.

Selective functionalization of aliphatic C–H bonds, ubiquitous in molecular structures, could allow ready access to diverse chemical products. While enzymatic oxygenation of C–H bonds is well established, the analogous enzymatic nitrogen functionalization is still unknown; nature is reliant on preoxidized compounds for nitrogen incorporation. Likewise, synthetic methods for selective nitrogen derivatization of unbiased C–H bonds remain elusive. In this work, new-to-nature heme-containing nitrene transferases were used as starting points for the directed evolution of enzymes to selectively aminate and amidate unactivated C­(sp3)–H sites. The desymmetrization of methyl- and ethylcyclohexane with divergent site selectivity is offered as demonstration. The evolved enzymes in these lineages are highly promiscuous and show activity toward a wide array of substrates, providing a foundation for further evolution of nitrene transferase function. Computational studies and kinetic isotope effects (KIEs) are consistent with a stepwise radical pathway involving an irreversible, enantiodetermining hydrogen atom transfer (HAT), followed by a lower-barrier diastereoselectivity-determining radical rebound step. In-enzyme molecular dynamics (MD) simulations reveal a predominantly hydrophobic pocket with favorable dispersion interactions with the substrate. By offering a direct path from saturated precursors, these enzymes present a new biochemical logic for accessing nitrogen-containing compounds.

We report the C–H activation of thioethers to α-thio alkyl radicals and their addition to electron-deficient olefins to afford alkylated products through dual photoredox and weak Brønsted base catalysis. Mechanistic studies are consistent with a two-step activation mechanism, where oxidation of thioethers to their corresponding sulfide radical cations by an acridinium photoredox catalyst is followed with deprotonation by trifluoroacetate to generate α-thio alkyl radicals and trifluoroacetic acid (TFA). Experimental studies support the involvement of TFA in all subsequent steps leading to product formation.

Herein, we detail a unified synthetic approach to the classical lignan family of natural products that hinges on divergence from a common intermediate that was strategically identified from nature's biosynthetic blueprints.

We report the C−H activation of thioethers to α-thio alkyl radicals and their addition to N-methoxyheteroarenium salts for the redoxneutral synthesis of α-heteroaromatic thioethers. Studies are consistent with a two-step activation mechanism, where oxidation of thioethers to sulfide radical cations by a photoredox catalyst is followed by α-C−H deprotonation by a weak Brønsted base catalyst to afford α-thio alkyl radicals. Further, N-methoxyheteroarenium salts play additional roles as a source of methoxyl radical that contributes to α-thio alkyl radical generation and a sacrificial oxidant that regenerates the photoredox catalytic cycle.