Synthesis of Cyclic N-Acyl Amidines by [3+2] Cycloaddition of N-Silyl Enamines and Activated Acyl Azides

In this study, we describe the synthesis of cyclic N-acyl amidines from readily available N-heteroarenes. The synthetic methodology utilized the versatile N-silyl enamine intermediates from the hydrosilylation of N-heteroarenes for the [3 + 2] cycloaddition reaction step. We evaluated various acyl azides and selected an electronically activated acyl azide, thereby achieving a reasonable yield of cyclic N-acyl amidines. We analyzed the relationship between the reactivity of each step and the electronic nature of substrates using in situ nuclear magnetic resonance spectroscopy. In addition, we demonstrated gram-scale synthesis using the proposed methodology.

Automated summary

This study presents a methodology for the synthesis of cyclic N-acyl amidines from easily accessible N-heteroarenes. The reaction utilizes N-silyl enamine intermediates, obtained through hydrosilylation, for the [3 + 2] cycloaddition step. By evaluating different acyl azides, a reasonable yield of cyclic N-acyl amidines was achieved. The reactivity of each step and the electronic nature of the substrates were analyzed using in situ nuclear magnetic resonance spectroscopy, providing insight into the reaction mechanism.