Construction of multiple bonds via a domino reaction of trifluoroacetimidoyl nitriles with in situ generated bis-nucleophiles

Abstract

A transition-metal-free double addition/double rearrangement domino reaction affording CF₃-substituted pyrimidines was developed, which enables the one-pot construction of five new bonds, namely three C–C bonds and two C–N bonds. The keys to achieve this highly efficient reaction include the delicate design of the bis-nucleophiles in situ generated from the dimerization of alkyl nitriles and the use of trifluoroacetimidoyl nitriles containing CN, CN, and CF₃ groups as the reactant. The mechanistic studies by the experiments and DFT calculations reveal that the transformation involves two addition and two unprecedented rearrangement processes.