Modular access to multi-substituted allenones via environmentally friendly organocatalytic C–H allenylation of aldehydes

Abstract

Direct C–H alkylation of aldehydes with organohalides has provided a straightforward and step-economical strategy for ketone synthesis. However, direct C–H allenylation of aldehydes with organohalides has not been reported and remains challenging. Herein, we demonstrate an N-heterocyclic carbene (NHC) organocatalytic direct C–H allenylation of aldehydes with propargyl bromides, providing a new platform for modular access to wide-ranging multi-substituted allenones. This protocol features environmentally friendly conditions (metal- and photocatalyst-free at room temperature and the use of a green solvent), a broad substrate scope (both aromatic and aliphatic substrates were well tolerated), readily accessible materials, and high regioselectivity. Moreover, this strategy might be attractive to the field of medicinal chemistry, considering its success in the construction of allenones bearing bioactive fragments via late-stage functionalization. Key to the success of this reaction relied on the Csp–C(O)sp² radical–radical coupling of the allenyl radicals instead of the propargyl radicals with the NHC-bound ketyl radicals, which was proved to be more favorable in terms of both kinetics and thermodynamics by DFT calculations.