配体调控的铜催化亚甲基环丙烷对映选择性双烯丙基化及开环烯丙基化反应

doi:10.1016/S1872-2067(26)65158-3

催化学报 ›› 2026, Vol. 89: 444-452.DOI: 10.1016/S1872-2067(26)65158-3

配体调控的铜催化亚甲基环丙烷对映选择性双烯丙基化及开环烯丙基化反应

袁洋^a, 葛方蓓^a, 吴小锋^a^,^b^,^*()

^a中国科学院大连化学物理研究所,大连洁净能源国家实验室,辽宁大连 116023,中国
^b莱布尼茨催化研究所,罗斯托克,德国

收稿日期:2026-01-16 接受日期:2026-02-22 出版日期:2026-10-18 发布日期:2026-09-01
通讯作者: *电子信箱: xwu2020@dicp.ac.cn (吴小锋).
基金资助:
国家重点研发项目(2023YFA1507500);国家自然科学基金(22572190);国家自然科学基金(22302198);国家自然科学基金(22571291);中国科学院战略性先导科技专项(XDB1530000)

Ligand-controlled divergent copper-catalyzed enantioselective dihydroallylation and ring-opening hydroallylation of methylenecyclopropanes

Yang Yuan^a, Fangbei Ge^a, Xiao-Feng Wu^a^,^b^,^*()

^aDalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences,Dalian 116023, Liaoning, China
^bLeibniz-Institut für Katalyse, Rostock 18059, Germany

Received:2026-01-16 Accepted:2026-02-22 Online:2026-10-18 Published:2026-09-01
Contact: *E-mail:xwu2020@dicp.ac.cn(X.-F. Wu).
Supported by:
National Key R&D Program of China(2023YFA1507500);National Natural Science Foundation of China(22572190);National Natural Science Foundation of China(22302198);National Natural Science Foundation of China(22571291);Strategic Priority Research Program of the Chinese Academy of Sciences(XDB1530000)

摘要/Abstract

摘要：

烯丙基结构单元广泛存在于天然产物、药物分子及功能材料中, 是构建分子多样性的重要合成砌块. 过渡金属催化的烯丙基化反应为高效引入烯丙基提供了有力手段, 其中铜氢(CuH)催化体系近年来发展迅速, 能够通过原位生成手性有机铜中间体, 实现对映选择性的碳碳键构建. 另一方面, 亚甲基环丙烷(MCPs)由于其显著的环张力和独特的反应活性, 在过渡金属催化下可发生β-碳消除等开环过程, 为构建多官能化骨架提供契机. 然而, 如何在同一催化体系中实现对亚甲基环丙烷的选择性开环与进一步官能团化, 并实现反应路径的可控, 仍具有挑战性. 基于此, 本文发展了一种配体调控的铜催化氢烯丙基化策略, 实现了亚甲基环丙烷与烯丙基磷酸酯的选择性转化, 为非共轭二烯及羰基化产物的构建提供了新方法.

本研究以CuCl为催化剂前体、硅烷为氢源, 在碱存在下原位生成CuH活性物种, 通过改变膦配体实现反应路径的可控分化. 当采用手性双膦配体(S,S)-Ph-BPE时, 反应经历开环氢烯丙基化-不对称氢烯丙基化串联过程, 高效构建手性1,9-二烯产物, 代表性底物3a的分离收率为73%, 对映选择性达99% ee; 底物适用范围广泛, 各类带有给电子基团或吸电子基团的芳基取代MCPs均能高效转化, 且一致地保持高对映选择性(93%->99% ee). 若将配体切换为Xantphos, 反应则停留在开环阶段, 专一性地通过单烯丙基化生成非共轭1,6-二烯, 收率达48%-63%. 机理实验表明, 该单烯丙基化中间体(S,S)-Ph-BPE存在下可进一步转化为手性双烯丙基化产物, 支持分步反应路径. 进一步的机理分析表明, 反应首先经历CuH对烯烃的插入形成环丙基甲基铜物种, 随后β-碳消除实现开环生成高烯丙基铜中间体, 经与烯丙基磷酸酯偶联得到1,6-二烯; 在手性配体作用下, 第二次区域与对映选择性氢铜化及烷基化过程生成1,9-二烯产物. 此外, 本体系可实现双组分不同烯丙基磷酸酯的一锅串联反应, 构建结构更复杂的手性二烯(93%->99% ee). 在10 bar CO压力条件下, 体系进一步拓展至羰基化氢烯丙基化反应, 成功合成α,β-不饱和酮以及手性酮化合物, 展现出良好的反应拓展性.

综上, 本工作实现了通过简单调控配体对铜催化反应路径的精准控制, 在同一体系中选择性获得1,6-或1,9-二烯产物, 并拓展至羰基化反应, 丰富了亚甲基环丙烷的官能化模式. 该策略为构建手性非共轭二烯和羰基化合物提供了高效平台, 也为发展可调控的铜氢催化串联反应提供了新的思路. 未来, 通过进一步发展新型手性配体和拓展底物类型, 有望实现更高效、更普适的张力环分子不对称转化.

关键词: 铜催化, 烯丙基化, 发散合成, 对映选择性, 羰基化

Abstract:

We report a tunable, ligand-controlled protocol for the copper-hydride-catalyzed functionalization of methylenecyclopropanes (MCPs) with allyl phosphates. This divergent methodology enables selective access to two distinct classes of unsaturated scaffolds, dictated by the specific phosphine ligand employed. When the chiral bisphosphine ligand (S,S)-Ph-BPE is utilized, the reaction proceeds via an enantioselective dihydroallylation cascade, affording nonconjugated chiral 1,9-dienes with high yields and excellent enantioselectivities (up to > 99% ee). Alternatively, switching the ligand to Xantphos confines the reaction at the ring-opening stage, selectively delivering nonconjugated 1,6-dienes via mono-allylation. Mechanistic studies support a stepwise pathway initiated by hydrocupration and β-carbon elimination, wherein the mono-allylated intermediate can be isolated and subsequently converted into the di-allylated product. The versatility of this platform is further demonstrated through a modular one-pot cascade employing two distinct allylic phosphates to generate structurally complex chiral dienes. Additionally, the catalytic system has been extended to carbonylative hydroallylation, providing efficient access to α,β-unsaturated ketones and chiral ketones. This strategy represents a robust approach for the stereoselective construction of diverse dienes and carbonyl-containing frameworks from strained ring systems.

Key words: Copper catalysis, Hydroallylation, Divergent Synthesis, Enantioselective, Carbonylation

袁洋, 葛方蓓, 吴小锋. 配体调控的铜催化亚甲基环丙烷对映选择性双烯丙基化及开环烯丙基化反应[J]. 催化学报, 2026, 89: 444-452.

Yang Yuan, Fangbei Ge, Xiao-Feng Wu. Ligand-controlled divergent copper-catalyzed enantioselective dihydroallylation and ring-opening hydroallylation of methylenecyclopropanes[J]. Chinese Journal of Catalysis, 2026, 89: 444-452.

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链接本文: https://www.cjcatal.com/CN/10.1016/S1872-2067(26)65158-3

https://www.cjcatal.com/CN/Y2026/V89/I10/444

图/表 8

Scheme 1. Copper hydride catalyzed hydroallylation of unsaturated C-C bonds. (a) CuH-catalyzed enantioselective hydroallylation of alkenes. (b) CuH-catalyzed anti-Markovnikov hydroallylation of alkynes. (c) This work: CuH-catalyzed selective hydroallylation of MCPs.

Table 1 Optimization of the reaction conditions a.

Entry	Variation from above conditions	Yield of 3a (%)	ee of 3a (%)	Yield of 4a (%)
1	None	87 (73)^b	99	trace
2	(MeO)₂MeSiH instead of PMHS	45	95	9
3	(EtO)₂MeSiH instead of PMHS	51	99	nd
4	THF instead of DME	85	99	12
5	1,4-Dioxane instead of DME	71	99	15
6	2a-1 instead of 2a	37	98	6
7	2a-2 instead of 2a	28	97	4
8	Without LiO^tBu	0	—	0
9	L2 instead of L1	trace	—	24
10	L3 instead of L1	trace	—	43
11	L4 instead of L1	5	nd	17
12	L5 instead of L1	0	—	54
13^c	L5 instead of L1	0	—	70 (61)^b

Scheme 2. Substrate scope for enantioselective dihydroallylation. Reaction conditions: 1 (0.1 mmol), 2 (0.3 mmol), CuCl (10 mol%), (S,S)-Ph-BPE (12 mol%), LiOtBu (3 equiv.), PMHS (4 equiv.), 30 °C and DME (0.5 mL). Isolated yields; ee’s were determined by chiral HPLC.

Scheme 3. Substrate scope for ring-open hydroallylation. Reaction conditions: 1 (0.1 mmol), 2 (0.15 mmol), CuCl (10 mol%), Xantphos (12 mol%), LiOtBu (2 equiv.), PhMe2SiH (3 equiv.), 30 °C and THF (0.5 mL). Isolated yields.

Scheme 4. One-pot cascade hydroallylation with two different allylic phosphates. Reaction conditions: 1a (0.1 mmol), allylic phosphate (0.15 mmol), CuCl (10 mol%), Xantphos (12 mol%), LiOtBu (2 equiv.), PhMe2SiH (3 equiv.), and THF (0.5 mL) were stirred at 30 °C for 20 h, then, the second allylic phosphate (0.15 mmol), CuCl (10 mol%), (S,S)-Ph-BPE (12 mol%), LiOtBu (0.2 mmol) and (MeO)2MeSiH (0.2 mmol) was added and the mixture was stirred for another 20 h. Isolated yields; ee’s were determined by chiral HPLC.

Scheme 5. Synthetic transformations.

Fig. 1. Proposed reaction pathways.

Scheme 6. Substrate scope for carbonylative hydroallylation. Reaction conditions: 1 (0.1 mmol), 2 (0.2 mmol), CuCl (10 mol%), (rac)-Segphos (12 mol%), LiOtBu (2 equiv.), PMHS (3 equiv.), 50 °C, DCE (0.5 mL) and CO (10 bar). a Reaction conditions: 1a (0.1 mmol), 2a (0.3 mmol), CuCl (10 mol%), (S,S)-Ph-BPE (12 mol%), LiOtBu (3 equiv.), PMHS (4 equiv.), 50 °C, DCE (0.5 mL) and CO (10 bar). Isolated yields, ee was determined by chiral HPLC.

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配体调控的铜催化亚甲基环丙烷对映选择性双烯丙基化及开环烯丙基化反应

Ligand-controlled divergent copper-catalyzed enantioselective dihydroallylation and ring-opening hydroallylation of methylenecyclopropanes

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