Substituent-controlled selective synthesis of N-acyl 2-aminothiazoles by intramolecular Zwitterion-mediated C-N bond cleavage.
Substituent-controlled selective synthesis of N-acyl 2-aminothiazoles by intramolecular Zwitterion-mediated C-N bond cleavage.
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DOI：
10.1021/jo502123k
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发表时间：
2014-11
期刊：
影响因子：
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通讯作者：
Yang Wang;F. Zhao;Yue Chi;Wen‐Xiong Zhang;Z. Xi
中科院分区：
文献类型：
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作者：
Yang Wang;F. Zhao;Yue Chi;Wen‐Xiong Zhang;Z. Xi
C-N键的断裂是现代有机合成中一个有趣而富有挑战性的课题。在烷基硫醇酸锂、大体积碳二亚胺和酸性氯化物之间的MCR反应中，我们首次实现了两性离子控制的C-N键断裂，合成了N-酰基2-氨基噻唑类化合物。这是一种简单、高效、通用的合成N-酰基-2-氨基噻唑类化合物的方法。N-酰基-2-氨基噻唑的选择性合成很大程度上依赖于碳二亚胺的空间位阻。这一结果与我们之前通过1，5-酰基迁移得到5-酰基-2-亚氨基噻唑的聚合反应形成了鲜明的对比。有趣的是，碳二亚胺上取代基的微小变化就可以完全改变产品结构。实验和理论结果证明了本体系C-N键断裂先于酰基迁移的原因。通过史无前例的Hofmann型消除的分子内氢继电器是这种全新的两性离子控制的C-N键断裂的关键。
The cleavage of C-N bonds is an interesting and challenging subject in modern organic synthesis. We have achieved the first zwitterion-controlled C-N bond cleavage in the MCR reaction among lithium alkynethiolates, bulky carbodiimides, and acid chlorides to construct N-acyl 2-aminothiazoles. This is a simple, highly efficient, and general method for the preparation of N-acyl 2-aminothiazoles with a broad range of substituents. The selective synthesis of N-acyl 2-aminothiazoles significantly depends on the steric hindrance of carbodiimides. The result is in striking contrast with our previous convergent reaction giving 5-acyl-2-iminothiazolines via 1,5-acyl migration. It is indeed interesting that the slight change of the substituents on the carbodiimides can completely switch the product structure. Experimental and theoretical results demonstrate the reason why the C-N bond cleavage in the present system is prior to the acyl migration. The intramolecular hydrogen relay via unprecedented Hofmann-type elimination is essential for this totally new zwitterion-controlled C-N bond cleavage.