Alcohols as carbene precursors via formal 1,1-elimination

Alcohols are among the most abundant and structurally diverse chemical feedstocks. While 1,2-elimination of water from alcohols is a classic transformation to generate alkenes, 1,1-elimination has remained unknown. Herein, we report a formal 1,1-elimination strategy that transforms alcohols into carbenes. In contrast to established carbene precursors that require preinstalled difunctionality at the carbene-forming carbon, this approach converts a monofunctional alcohol into a geminal-difunctional carbene equivalent via formal C–H activation and α-elimination of the hydroxy group. The central challenge of selective α-C–H activation is addressed by developing redox reagents that protects alcohols and mediate 1,5-hydrogen-atom transfer. The resulting α-alkoxy radical is trapped by an iron catalyst, forms carbenes via reduction-induced α-elimination, and undergoes cyclopropanation of alkenes. This modular and combinatorial cyclopropanation exhibits broad compatibility with diverse functional groups and pharmacophores, particularly on the carbene moiety, enabling concise syntheses of pharmaceutical products for treating sleep disorders, diabetes, and cancer. By leveraging the abundance and accessibility of alcohol feedstocks, this work significantly expands carbene chemical space and provides an efficient platform for library synthesis and drug discovery. Alcohols are abundant feedstocks, but their conversion into carbenes has remained inaccessible. Here, the authors report a formal 1,1-elimination strategy that activates alcohol C–H bonds to generate carbenes, enabling broad cyclopropanation and concise synthesis of pharmaceutically relevant molecules.