Synthesis of aza-β-lactams via B(C6F5)3-catalyzed Wolff rearrangement/[2+2] cascade cyclization of α-diazoketones with diazenes

Abstract

The development of efficient, metal-free routes to aza-β-lactams is a significant pursuit in synthetic and medicinal chemistry. Herein, we report a novel, one-pot cascade strategy for the synthesis of aza-β-lactams via a B(C6F5)3-catalyzed Wolff rearrangement/[2+2] cyclization of α-diazoketones with diazenes. This method leverages the strong Lewis acidity of B(C6F5)3 to catalytically generate ketene intermediates from α-diazoketones under mild conditions. Subsequent formal [2+2] cyclization with diazenes, underexplored as 2π-components, directly affords the coveted aza-β-lactams. This operationally simple protocol proceeds efficiently at room temperature, tolerates a range of functional groups, and provides a versatile and step-economical pathway to diverse aza-β-lactams architectures in good yields, showcasing the power of borane catalysis in complex heterocycle synthesis. These reactions were also performed on a gram-scale.