Stereocontrolled Synthesis of Cyclobutylamines Enabled by Lewis Acid-Catalyzed (3 + 2 + 2) Cycloaddition/Ring-Opening Strategy of Bicyclo[1.1.0]butanes with Triazinanes

Abstract

Herein, we develop a modular and efficient “cycloaddition/ring-opening” strategy of bicyclo[1.1.0]butanes (BCBs) with triazinanes to provide a series of syn-diastereoselective cyclobutylamines via 2,4-diazabicyclo[4.1.1]octanes (aza-BCOs). The reaction features simple operation, mild reaction conditions, and a broad substrate scope. Mechanistic studies suggest that the cycloaddition follows a stepwise (3 + 2 + 2) rather than (4 + 3) cycloaddition, involving an S_N2 nucleophilic addition of formaldimine to Lewis acid-activated BCB species. A scale-up experiment and various synthetic transformations of the product further highlight the synthetic utility. We expect that our findings will encourage the exploration of BCB chemistry to access more synthetically challenging cyclobutane frameworks.