Pendant Alkoxy Groups on N-Aryl Substitutions Drive the Efficiency of Imidazolylidene Catalysts for Homoenolate Annulation from Enal and Aldehyde

Angew Chem Int Ed Engl. 2020 Oct 19;59(43):19031-19036. doi: 10.1002/anie.202008631. Epub 2020 Aug 20.


Hydrogen-transfer in the tetrahedral intermediate generated from an imidazolylidene catalyst and α,β-unsaturated aldehyde forms a conjugated Breslow intermediate. This is a critical step affecting the efficiency of the NHC-catalyzed γ-butyrolactone formation via homoenolate addition to aryl aldehydes. A novel type of imidazolylidene catalyst with pendant alkoxy groups on the ortho-N-aryl groups is described. Catalyst of this sort facilitates the formation of the conjugated Breslow intermediate. Studies of the rate constants for homoenolate annulation affording γ-butyrolactones, reveal that introduction of the oxygen atoms in the appropriate position of the N-aryl substituents can increase the efficiency of imidazolylidene catalysts. Structural and mechanistic studies revealed that pendant alkoxy groups can be located close to the proton of the tetrahedral intermediate, thereby facilitating the proton transfer.

Keywords: N-heterocyclic carbenes; annulation; kinetic study; organocatalysis; umpolung.