铜催化烯丙位C—H键不对称氧化反应

doi:10.6023/cjoc202605030

有机化学 ›› 2026, Vol. 46 ›› Issue (9): 3630-3639.DOI: 10.6023/cjoc202605030 上一篇下一篇

研究论文

铜催化烯丙位C—H键不对称氧化反应

李家圆, 陈品红, 刘国生^*()

中国科学院上海有机化学研究所沪港化学合成联合实验室新基石科学实验室上海 200032

收稿日期:2026-05-30 修回日期:2026-07-13 发布日期:2026-07-23
基金资助:
国家重点研发计划(2021YFA1500100); 中国科学院战略性先导科技专项(XDB0610000); 国家自然科学基金(22331012); 国家自然科学基金(22561160127); 国家自然科学基金(92256301); 上海市基础研究先行区计划和新基石科学基金会资助项目.

Copper-Catalyzed Enantioselective Oxidation of Allylic C—H Bonds

Jiayuan Li, Pinhong Chen, Guosheng Liu^*()

New Cornerstone Science Laboratory, State Key Laboratory of Organometallic Chemistry, and Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032

Received:2026-05-30 Revised:2026-07-13 Published:2026-07-23
Contact:
^* E-mail: gliu@mail.sioc.ac.cn
About author:
Dedicated to the 100th anniversary of the birth of Professor Xikui Jiang.
Supported by:
National Key R&D Program of China(2021YFA1500100); Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0610000); National Nature Science Foundation of China(22331012); National Nature Science Foundation of China(22561160127); National Nature Science Foundation of China(92256301); Shanghai Pilot Program for Basic Research and the New Cornerstone Science Foundation.

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摘要/Abstract

烯丙位C—H键的不对称氧化是构建手性烯丙醇及其衍生物的重要策略, 但由于C—H键惰性高及立体选择性控制困难, 该转化极具挑战性. 发展了一种铜催化芳基烯烃烯丙位C—H键的不对称氧化反应, 实现了以简单烯烃为限制试剂直接构建手性烯丙酯的方法. 该反应条件温和, 具有良好的官能团兼容性与底物普适性, 能够以中等至良好的收率及良好到优秀的对映选择性获得手性烯丙酯产物.

关键词: 烯丙位C—H键氧化, 不对称催化, 铜催化, 氢原子转移, 手性烯丙酯

Enantioselective allylic C—H oxidation represents an attractive strategy for the synthesis of chiral allylic oxygenated compounds. However, the development of catalytic asymmetric variants remains challenging due to the inherent inertness of C—H bonds and the difficulty in controlling stereoselectivity during C—H functionalization. A copper-catalyzed enantioselective allylic C—H oxidation, which allows the direct preparation of chiral allylic esters starting from simple alkenes, is reported. The reaction employs a chiral ligand-supported copper catalyst in combination with an N-Cl reagent to generate an N-centered radical capable of selective hydrogen atom transfer (HAT) to the allylic position of alkenes, forming an allylic radical intermediate. Subsequent capture of this radical by a copper-carboxylate species enables enantioselective C—O bond formation, affording the desired chiral allylic esters. The transformation proceeds under mild conditions and exhibits a broad substrate scope, accommodating both cyclic and acyclic alkenes with moderate to good yields and high levels of enantioselectivity. Notably, the reaction can be conducted with the alkene as the limiting reagent, addressing a common limitation of traditional allylic oxidation methods.

Key words: allylic C—H oxidation, asymmetric catalysis, copper catalysis, hydrogen atom transfer (HAT), chiral allylic ester

引用此文

李家圆, 陈品红, 刘国生. 铜催化烯丙位C—H键不对称氧化反应[J]. 有机化学, 2026, 46(9): 3630-3639.

Jiayuan Li, Pinhong Chen, Guosheng Liu. Copper-Catalyzed Enantioselective Oxidation of Allylic C—H Bonds[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3630-3639.

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图/表 4

图式1. sp3-C—H键不对称氧化反应

Scheme 1. Enantioselective sp3-C—H oxidation

Entry	Ligand	Salt	Yield^b/%	ee^c/%	r.r.^d
1	L1	AgOPiv	10	0	n.d.
2	L1	NaOPiv	0	—	—
3	L1	KOPiv	0	—	—
4	L2	AgOPiv	0	—	—
5	L3	AgOPiv	0	—	—
6	L4	AgOPiv	4	n.d.	n.d.
7	L5	AgOPiv	55	89	11∶1
8	L6	AgOPiv	25	60	10∶1
9^e	L5	AgOPiv	40	71	10∶1
10^f	L5	AgOPiv	16	80	11∶1
11^g	L5	AgOPiv	73	90	11∶1

表1. 反应条件优化a

Table 1. Optimization of the reaction conditions

表2. 烯丙基C—H键不对称氧化反应的底物范围a,b,c

Table 2. Substrate scope of enantioselective allylic C—H oxidation

图式2. 反应可能的机理

Scheme 2. Proposed reaction mechanism

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铜催化烯丙位C—H键不对称氧化反应

Copper-Catalyzed Enantioselective Oxidation of Allylic C—H Bonds

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