An Accesss to 4,5,6-Trisubstituted Pyrimidines from 2H-Azirines and -Isocyanoacetates or -Isocyanoacetamides Enabled by 1,3-Dipolar [3+2] Cycloaddition/Ring-Expanding/Oxidative Aromatization Process

The products containing pyrimidine scaffolds exhibit various important physiological and biological activities. To date, the strategies to generate 4,5,6-trisubstituted pyrimidines were not reported. Here, a copper-catalyzed reaction of 2H-azirines with alpha-isocyanoacetates or alpha-isocyanoacetamides has been developed, rapidly preparing 4,5,6-trisubstituted pyrimidines. The mechanistic results reveal that this strategy underwent a formal 1, 3-dipolar [3 + 2] cycloaddition/ring-expanding/oxidative aromatization procedure to construct the desired pyrimidines.