Willard Henry Dow Laboratory, Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.
Nat Commun. 2019 Nov 8;10(1):5095. doi: 10.1038/s41467-019-13072-x.
Azetidines are four-membered nitrogen-containing heterocycles that hold great promise in current medicinal chemistry due to their desirable pharmacokinetic effects. However, a lack of efficient synthetic methods to access functionalized azetidines has hampered their incorporation into pharmaceutical lead structures. As a [2+2] cycloaddition reaction between imines and alkenes, the aza Paternò-Büchi reaction arguably represents the most direct approach to functionalized azetidines. Hampered by competing reaction paths accessible upon photochemical excitation of the substrates, the current synthetic utility of these transformations is greatly restricted. We herein report the development of a visible light-enabled aza Paternò-Büchi reaction that surmounts existing limitations and represents a mild solution for the direct formation of functionalized azetidines from imine and alkene containing precursors.
氮杂环丁烷是一种四元含氮杂环化合物，由于其理想的药代动力学效应，在当前的药物化学中具有很大的应用前景。然而，缺乏有效的合成方法来获得功能化的氮杂环丁烷，这阻碍了它们在药物先导结构中的应用。氮杂 Paternò-Büchi 反应作为亚胺和烯烃之间的[2+2]环加成反应，可以说是获得功能化氮杂环丁烷的最直接的方法。由于底物的光化学激发可获得竞争反应途径，这些转化的当前合成实用性受到了极大的限制。在此，我们报告了可见光促进的氮杂 Paternò-Büchi 反应的开发，该反应克服了现有限制，为直接从含亚胺和烯烃的前体形成功能化氮杂环丁烷提供了一种温和的解决方案。
