Detailed kinetic analysis for the Cu(I)-catalyzed Kinugasa reaction forming β-lactams has revealed an anomalous overall zero-order reaction profile, due to opposing positive and negative orders in nitrone and alkyne, respectively. Furthermore, the reaction displays a second-order dependence on the catalyst, confirming the critical involvement of a postulated bis-Cu complex. Finally, reaction progress analysis of multiple byproducts has allowed a new mechanism, involving a common ketene intermediate to be delineated. Our results demonstrate that β-lactam synthesis through the Kinugasa reaction proceeds via a cascade involving (3 + 2) cycloaddition, (3 + 2) cycloreversion, and finally (2 + 2) cycloaddition. Our new mechanistic understanding has resulted in optimized reaction conditions to dramatically improve the yield of the target β-lactams and provides the first consistent mechanistic model to account for the formation of all common byproducts of the Kinugasa reaction.

中文翻译：

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修改后的衣笠反应机理

Cu（I）催化的衣笠反应形成 β-内酰胺的详细动力学分析表明，由于硝酮和炔烃的正负顺序相反，整体零级反应曲线异常。此外，该反应显示出对催化剂的二级依赖性，证实了假定的双铜配合物的关键参与。最后，对多种副产物的反应进程分析允许一种新的机制，涉及一种常见的乙烯酮中间体被描绘出来。我们的结果表明，通过 Kinugasa 反应合成 β-内酰胺是通过级联反应进行的，包括 (3 + 2) 环加成、(3 + 2) 环还原和最后的 (2 + 2) 环加成。