Organocatalytic activation of isocyanides: N-heterocyclic carbene-catalyzed enaminone synthesis from ketones† †Electronic supplementary information (ESI) available: Full data for reaction conditions optimizations, detailed experimental procedures, and full characterization of substrates and products. Crystallographic data for compound 3sa. CCDC 1503347. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6sc05266e Click here for additional data file. Click here for additional data file.

The first example of the use of an N-heterocyclic carbene (NHC) as an organocatalyst for the activation of isocyanides was demonstrated. On the basis of previous reports on the interaction between NHCs and isocyanides, we developed a catalytic cycle involving transient imidoyl intermediate. The reaction of ketones with isocyanides produced the corresponding enaminones with high efficiency. Control experiments suggested a novel role for the carbene in the activation of isocyanides, and a proton transfer process was found to be crucial for the generation of two activated species in the catalytic cycle. Various enaminones, some of which are not easily accessible by other methods, were synthesized in excellent yields. This study clearly demonstrates the potential of the nucleophilic activation of isocyanides in the expansion of their reactivity scope.