Eva Lin

Metallocarbenes are powerful intermediates for constructing complex molecular architectures, yet their generation typically relies on hazardous diazo or ylide precursors. We report photocatalytic and electrochemical strategies for direct carbene formation from unmodified carbonyl compounds using a low-valent iron system. The reaction proceeds through net oxidative addition of Fe(I) into the carbonyl bond, followed by α-protonation and α-elimination to generate a reactive Fe–carbene intermediate. This platform enables cyclopropanation of diverse alkenes─including complex, drug-like, and amino-acid-derived substrates─under mild conditions, delivering highly functionalized, sp³-rich products. Mechanistic studies reveal direct carbonyl activation rather than free radical intermediacy, with a concerted–asynchronous olefin addition pathway. These findings establish a general strategy for carbonyl-to-carbene conversion, expanding the scope of base-metal catalysis and providing a blueprint for redefining carbonyl activation in synthetic chemistry.

Alcohols and aryl carboxylic acids are among the most commercially abundant, synthetically versatile, and operationally convenient building blocks in organic chemistry. Despite their widespread availability, the direct formation of C(sp³)-C(sp²) bonds from these functional groups remains a challenge. Recently, our group developed robust protocols to harness alcohols as alkyl radical precursors, but the activation of aryl acids remains relatively unexplored. Herein, we describe the merger of N-heterocyclic carbene (NHC)-mediated deoxygenation and nickel-mediated decarbonylation of aryl acids toward C(sp³)-C(sp²) bond formation. The utility of this method is demonstrated through the synthesis of a diverse range of aryl-alkyl cross-coupled products and the late-stage functionalization of complex molecules, including drugs, natural products, and biomolecules.

Copper complexes are widely used in the synthesis of fine chemicals and materials to catalyze couplings of heteroatom nucleophiles with aryl halides. We show that cross-couplings catalyzed by some of the most active catalysts occur by a mechanism not previously considered. Copper(II) [Cu(II)] complexes of oxalamide ligands catalyze Ullmann coupling to form the C–O bond in aryl ethers by concerted oxidative addition of an aryl halide to Cu(II) to form a high-valent species that is stabilized by radical character on the oxalamide ligand. This mechanism diverges from those involving Cu(I) and Cu(III) intermediates that have been posited for other Ullmann-type couplings. The stability of the Cu(II) state leads to high turnover numbers, >1000 for the coupling of phenoxide with aryl chloride electrophiles, as well as an ability to run the reactions in air.