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

Abstract

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.

Keywords

• [3 + 2] cycloaddition
• <i>N</i>-silyl enamine
• B(C₆F₅)₃
• tetrahydroisoquinoline
• acyl azide
• spectroscopic analysis