Functionalized azetidines via visible light-enabled aza Paterno-Buchi reactions
Functionalized azetidines via visible light-enabled aza Paterno-Buchi reactions
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DOI：
10.1038/s41467-019-13072-x
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发表时间：
2019-11-08
影响因子：
16.6
通讯作者：
Schindler, Corinna S.
中科院分区：
文献类型：
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作者：
Becker, Marc R.;Richardson, Alistair D.;Schindler, Corinna S.
氮杂环丁烷是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广阔的前景。然而，缺乏有效的合成方法来获得官能化氮杂环丁烷阻碍了它们纳入药物先导结构。作为亚胺和烯烃之间的[2+2]环加成反应，氮杂Paterno-Buchi反应可以说代表了官能化氮杂环丁烷的最直接方法。由于底物光化学激发时可达到的竞争反应路径的阻碍，这些转化的当前合成效用受到极大限制。我们在此报告了可见光驱动的氮杂帕特诺-布奇反应的发展，该反应克服了现有的限制，并代表了从含亚胺和烯烃的前体直接形成官能化氮杂环丁烷的温和解决方案。
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 Paterno-Buchi 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 Paterno-Buchi reaction that surmounts existing limitations and represents a mild solution for the direct formation of functionalized azetidines from imine and alkene containing precursors.