Proton or Carbene Transfer? On the Dark and Light Reaction of Diazoalkanes with Alcohols

The formal alkylation reaction of OH groups with diazoalkanes under catalyst‐free reaction conditions finds broad application in organic synthesis. However, even today, this reaction is mainly limited to the use of diazomethane as reaction partner. In this combined experimental and theoretical study, we aim at a fundamental understanding of the reaction of diazoalkanes with alcohols to make this transformation amenable to a generalized approach towards formal alkylation reactions of alcohols with diazoalkanes. Experimental and theoretical studies suggest a direct proton transfer only in exceptional cases. In a more general setting, such O−H functionalization proceed both under dark and photochemical conditions via a key hydrogen‐bonded singlet carbene intermediate that undergoes a protonation–addition mechanism. We conclude with applications of this approach in O−H functionalization reactions of alcohols, including simple fluorinated, halogenated and aliphatic alcohols and showcase functional‐group tolerance of this method in the reaction of biologically active and pharmaceutically relevant alcohols.