Yang Zhanhui, Li Siqi, Zhang Zhong, Xu Jiaxi
State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing University of Chemical Technology, Beijing 100029, P. R. China.
Org Biomol Chem. 2014 Dec 28;12(48):9822-30. doi: 10.1039/c4ob01454e.
The base-switched annuloselectivity, namely [2 + 2] and [2 + 2 + 2] selectivity, in the reactions of ethyl malonyl chloride and imines is successfully realized. In the presence of the weak nucleophilic base 2-chloropyridine, the reactions deliver ethyl trans-β-lactam-3-carboxylates as the exclusive [2 + 2] products in up to 93% yields, while with the strong nucleophilic N-methylimidazole as the base, the reactions give rise to 2,3-dihydro-1,3-oxazin-4-one derivatives as the sole products in up to 99% yields via the formal [2 + 2 + 2] cycloaddition involving one molecule of the imine and two molecules of the ketene generated from malonyl chloride. Notably, ethyl trans-β-lactam-3-carboxylates are synthesized for the first time directly from the reactions of ethyl malonyl chloride and imines. Mechanistic discussions reveal that the annuloselectivity is controlled by the nucleophilicity of organic bases.
在丙二酸乙酯氯与亚胺的反应中成功实现了碱切换的环化选择性，即[2 + 2]和[2 + 2 + 2]选择性。在弱亲核碱2 - 氯吡啶存在下，反应以高达93%的产率得到反式β - 内酰胺 - 3 - 羧酸乙酯作为唯一的[2 + 2]产物，而以强亲核的N - 甲基咪唑作为碱时，反应通过涉及一分子亚胺和两分子由丙二酸氯生成的乙烯酮的形式上的[2 + 2 + 2]环加成反应，以高达99%的产率得到2,3 - 二氢 - 1,3 - 恶嗪 - 4 - 酮衍生物作为唯一产物。值得注意的是，反式β - 内酰胺 - 3 - 羧酸乙酯首次直接由丙二酸乙酯氯与亚胺的反应合成。机理讨论表明，环化选择性受有机碱亲核性的控制。
