非对称氮杂环丁烷的区域选择性开环反应

陈兴鹏; 许家喜*

doi:10.7536/PC160917

化学进展 ›› 2017, Vol. 29 ›› Issue (2/3) :181-197 DOI: 10.7536/PC160917

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非对称氮杂环丁烷的区域选择性开环反应

陈兴鹏, 许家喜*

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Regioselective Ring-Opening Reactions of Unsymmetric Azetidines

Xingpeng Chen, Jiaxi Xu*

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摘要

本文系统总结了非对称氮杂环丁烷的区域选择性开环反应。氮杂环丁烷的开环反应主要包括亲核开环、Stevens重排扩环及消除开环反应等。其中，亲核开环反应是氮杂环丁烷的主要开环方式。开环的区域选择性与氮杂环丁烷取代基结构密切相关。氮杂环丁烷相对比较稳定，其开环通常需要路易斯酸催化或者先转化成季铵盐才可以发生，因此，其开环反应的区域选择性受电子效应的影响比较明显。邻位带有不饱和官能团的氮杂环丁烷及其季铵盐一般发生氮原子与带有不饱和官能团的碳原子之间化学键的断裂，这是因为如芳基、烯基、氰基、酰基、甲酸酯基和甲酰胺基等不饱和官能团的共轭效应可以稳定其连接的碳原子在开环时形成的过渡态或者中间体，使该C-N键更容易断裂。如亲核开环反应，亲核试剂一般进攻芳甲位、烯丙位或连有氰基或甲酸酯基或甲酰胺基的邻位碳原子，电子效应起主要作用。对于2-烷基取代的氮杂环丁烷及其季铵盐，大位阻或者亲核性强的亲核试剂的开环反应一般发生在位阻小的氮邻位碳原子，空间效应起主要作用。分子内的亲核开环反应主要受反应过程中环大小的控制，一般有利于经过三元环、五元环、六元环和七元环过程开环得到开环产物。氮杂环丁烷是一类非常重要的含氮杂环化合物，通过总结和分析氮杂环丁烷的开环反应及其区域选择性，可以更好地认识和利用这类反应，通过有效地预测和控制开环反应的方向，来制备所需的有机化合物。希望本文能够促进氮杂环丁烷开环反应在有机化学中的发展与应用。

Abstract

Regioselective ring-opening reactions of unsymmetric azetidines are systematically summarized and reviewed in this paper. Ring-opening reactions of unsymmetric azetidines include nucleophilic ring opening, Stevens rearrangement and ring expansion, and elimination reactions. Nucleophilic ring-opening reactions are major ring opening reactions of azetidines. The regioselectivity in ring-opening reactions is closely related to the structure of substituents of azetidines. Azetidines are relatively stable and often require Lewis acid catalysis or converted into their quaternary ammonium salts when they undergo ring-opening reactions. Thus, their ring-opening reactions are more susceptible to electronic effects. Azetidines and azetidiniums with 2-unsaturated substituents often undergo cleavage of the C-N bond between the nitrogen atom and carbon atom with the unsaturated groups, because the unsaturated groups such as aryl, 1-alkenyl, cyano, carboxylate, and carboxamide groups possess the conjugative effects with their adjacent carbon atom, stabilizing the generated transition states or intermediates in the ring-opening reactions. So that their C-N bond is more easily broken. In nucleophilic ring opening reactions of azetidines, nucleophiles generally attack arylmethylic, allylic, cyano, acyl, carboxylate, and carboxamide-attached nitrogen-adjacent carbon atoms, controlled by the electronic effect. However, sterically bulky or strong nucleophiles usually attack the less substituted nitrogen adjacent carbon atom of 2-alkylazetidines and azetidiniums in their ring opening reactions, controlled by steric hindrance. The structure of products in intramolecular nucleophilic ring opening reactions of azetidines is controlled by the ring size in the reaction processes, the ring-opening reactions favorably undergo through three-membered ring, five-membered ring, six-membered ring and seven-membered ring processes. Azetidines are a class of very important nitrogen-containing heterocyclic compounds. We can better understand and utilize this kind of reactions by summarizing and analyzing the ring-opening reactions and their regioselectivity of unsymmetric azetidines. The desired compounds can be prepared efficiently after predicting and controlling the regioselectivity in ring-opening reactions of azetidines. We hope that the summarized conclusions can promote the development and application of ring-opening reactions of azetidines in organic synthesis.

Contents
1 Nucleophilic ring-opening reactions of azetidines
1.1 Nucleophiles in group C
1.2 Nucleophiles in group N
1.3 Nucleophiles in group O
1.4 Halogen nucleophiles
1.5 Hydride nucleophiles
2 Stevens rearrangement and ring enlargement of azetidines
2.1 Base-catalyzed Stevens rearrangement and ring enlargment
2.2 Stevens rearrangement and ring enlargement of azetidines and carbenes
3 Eliminating ring-opening reactions
3.1 Transition metal-catalyzed eliminating ring-opening reactions
3.2 Sterically hindered strong base-promoted eliminating ring-opening reactions
3.3 Thermal elimination of azetidines
4 Miscellaneous ring-opening reactions of azetidines
4.1 Reductive ring-opening reactions
4.2 Cleaving ring-opening reactions
5 Conclusion

Graphical abstract

关键词

氮杂环丁烷 / 开环反应 / 区域选择性 / 亲核反应

Key words

azetidine / ring-opening reaction / regioselectivity / nucleophilic reaction

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引用格式 ▾

陈兴鹏, 许家喜*. 非对称氮杂环丁烷的区域选择性开环反应[J]. 化学进展, 2017, 29(2/3): 181-197 DOI:10.7536/PC160917

Xingpeng Chen, Jiaxi Xu*. Regioselective Ring-Opening Reactions of Unsymmetric Azetidines[J]. Progress in Chemistry, 2017, 29(2/3): 181-197 DOI:10.7536/PC160917

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