仿生不对称催化烯烃双羟化反应研究进展

doi:10.6023/cjoc202504015

摘要/Abstract

高效、高选择性、环境友好的烯烃顺式双羟化催化体系的开发一直是合成化学及催化化学领域的重要研究目标. 自然界中的非血红素铁依赖型Rieske双加氧酶为此提供了经典范例, 这类酶能够实现芳烃的有氧区域选择性和立体选择性顺式双羟化反应——这是芳香化合物降解过程中的关键步骤. 该酶能将O₂分子的两个氧原子精准地引入产物, 生成顺式-1,2-二醇. 受Rieske双加氧酶的结构特征和反应机制的启发, 研究人员设计开发了非血红素铁和锰配合物作为其功能模拟物. 这些配合物能有效催化烯烃的不对称顺式双羟化反应, 选择性生成顺式-1,2-二醇. 本文重点介绍了近年来基于仿生策略的非血红素铁、锰配合物在不对称顺式双羟化反应中的研究进展, 并对相关反应机制进行了探讨.

关键词: 仿生催化, Rieske双加氧酶, 不对称双羟化, 高价金属-氧中间体, 非血红素金属配合物

The development of efficient, selective and environmentally friendly catalytic systems for olefin cis-dihydr- oxylation remains a key objective in synthetic and catalytic chemistry. Naturally occurring Rieske dioxygenases, nonheme iron-dependent enzymes, exemplify this transformation by enabling aerobic, regio-, and stereoselective cis-dihydroxylation of arenes—a critical step in aromatic degradation. These enzymes incorporate both oxygen atoms from O₂ into the cis- dihydrodiol product with high precision. Inspired by the structural and mechanistic features of Rieske dioxygenases, synthetic nonheme iron and manganese complexes have been designed as functional mimics. These complexes effectively mediate asymmetric cis-dihydroxylation of olefins, selectively yielding cis-dihydrodiol products. This review highlights the recent progress in bioinspired nonheme iron and manganese complexes for asymmetric cis-dihydroxylation, along with proposed reaction mechanisms.

Key words: biomimetic catalysis, Rieske dioxygenases, asymmetric cis-dihydroxylation, high-valent metal-oxygen species, nonheme metal complexes

引用此文

刘欣, 郑世鑫, 赵华杰, 陈洁, 王斌. 仿生不对称催化烯烃双羟化反应研究进展[J]. 有机化学, 2025, 45(12): 4257-4270.

Xin Liu, Shixin Zheng, Huajie Zhao, Jie Chen, Bin Wang. Recent Advances in Biomimetic Asymmetric Catalysis for Olefin cis-Dihydroxylation[J]. Chinese Journal of Organic Chemistry, 2025, 45(12): 4257-4270.

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图/表 20

图1. 手性顺式-1,2-二醇结构及Sharpless不对称双羟化

Figure 1. Enantioenriched cis-1,2-diols and Sharpless asymmetric dihydroxylation

图2. (A)萘双加氧酶中的电子传输链、(B) Rieske双加氧酶活性位点结构示意图、(C)假单胞菌属萘双加氧酶铁活性位点的三维结构[从左到右依次为: 萘双加氧酶与底物(PDB ID: 1O7G)、萘双加氧酶与O2 (PDB ID: 1O7M)和萘双加氧酶与产物(PDB ID: 1O7P)的复合物, 原子颜色标注: 紫色为铁、蓝色为氮、红色为氧、金色为碳]

Figure 2. (A) Electron transfer chain in NDO, (B) schematic structure of the active site of a Rieske dioxygenase, and (C) iron active site in NDO (Pseudomonas putida) during catalysis [left to right: Substrate-bound (PDB ID: 1O7G), O2-bound (PDB ID: 1O7M), and product-bound (PDB ID: 1O7P) states; Color code: violet=Fe, blue=N, red=O, gold=C]

图式1. 萘双加氧酶(NDO)可能的催化反应机理

Scheme 1. Proposed mechanistic pathways for NDO

图式2. 第一例非血红素铁催化烯烃顺式双羟化反应

Scheme 2. The first example of a nonheme iron complex that catalyzes olefin cis-dihydroxylation

Entry	Substrate	TON^a			RC^b/%
Entry	Substrate	cis-Diol	Epoxide	cis-Diol/Epoxide	RC^b/%
1	Styrene	8.0	0.1	80	—
2	1-Octene	7.6	0.1	76	—
3	Cyclohexene	6.2	0.7	9	—
4	cis-2-Heptene	4.9	0.7	7	99
5	trans-2-Heptene	4.9	0.5	10	˃ 99
6	Ethyl trans-crotonate	7.4	—	˃ 100	—
7	tert-Butyl acrylate	5.5	—	˃ 100	—
8	Dimethyl fumarate	5.3	—	˃ 100	—

表1. 底物限制量条件下配合物2催化各种烯烃氧化反应

Table 1. Catalytic oxidation of various olefins by 2 under substrate-limiting conditions

Entry	Substrate	Yield^a/%			RC^b/%
Entry	Substrate	cis-Diol	Epoxide	cis-Diol/Epoxide	RC^b/%
1	1-Octene	67	20	3.4	—
2	1-Decene	62	18	3.4	—
3	Vinylcyclohexane	57	16	3.6	—
4	Cyclohexene	45	30	1.5	—
5	cis-2-Heptene	60	20	3.0	97
6	trans-2-Heptene	61	14	4.4	99

表2. 底物限制量条件下配合物3催化各种烯烃氧化反应

Table 2. Catalytic oxidation of various olefins by 3 under substrate-limiting conditions

图3. 用于催化烯烃不对称双羟化反应的非血红素铁配合物

Figure 3. Nonheme iron complexes utilized in asymmetric cis-dihydroxylation of olefins

Entry	Complex	Labile site	Substrate	TON^a			ee/%
Entry	Complex	Labile site	Substrate	cis-Diol	Epoxide	cis-Diol/Epoxide	ee/%
1	4^b	Two cis-α	trans-2-Heptene	0.3	5.4	0.055	29
2	5^c	Two cis-β	trans-2-Heptene	7.5	2.4	3.1	79
3			cis-2-Heptene	7.8	4.5	1.7	9
4			1-Octene	8.1	1.3	6.2	60
5			tert-Butyl acrylate	10	0.5	20	23
6	6^d	Two cis-α	trans-2-Heptene	1.1	5.1	0.22	38
7			1-Octene	1.7	2.6	0.67	11
8			tert-Butyl acrylate	0.1	3.0	0.033	—
9	7^d	Two cis-α	trans-2-Heptene	5.2	0.2	26	97
10			cis-2-Heptene	3.4	0.6	5.7	11
11			1-Octene	6.4	0.1	64	76
12			Styrene	6.5	<0.1	>65	15
13			tert-Butyl acrylate	4.0	<0.1	>40	68
14			Ethyl trans-crotonate	7.5	0.1	>75	78
15	8^d	Two cis-α	trans-2-Heptene	3.6	0.9	4	78
16			1-Octene	4.6	0.5	9	29
17			tert-Butyl acrylate	2.7	<0.1	>27	23

表3. 烯烃大大过量条件下的非血红素铁催化不对称双羟化

Table 3. Nonheme iron-catalyzed asymmetric cis-dihydroxylation in the presence of a large excess of olefins

图4. 带有线性四齿氮配体的八面体立体异构铁配合物的配位模式

Figure 4. Coordination modes for octahedral stereogenic-at-iron complexes with linear N4 ligand

图式3. 经由假定三价铁-过氧氢中间体的非血红素铁催化以双氧水为氧源的烯烃不对称双羟化反应

Scheme 3. Nonheme iron-catalyzed asymmetric cis-dihydroxy- lation of olefins with H2O2 via a putative FeIII—OOH intermediate

图式4. 非血红素铁配合物催化以H2O2为氧化剂的烯烃环氧化与双羟化的可能反应机理

Scheme 4. Proposed pathways for olefin epoxidation and cis-dihydroxylation mediated by nonheme iron complex and H2O2 (Sol=CH3CN or CH3OH)

图式5. 非血红素铁催化三取代烯烃不对称双羟化反应

Scheme 5. Nonheme iron-catalyzed asymmetric cis-dihydroxy- lation of trisubstituted olefins

图5. 用于催化烯烃不对称双羟化反应的非血红素锰配合物

Figure 5. Nonheme manganese complexes utilized in asymmetric cis-dihydroxylation of olefins

图式6. 抗衡离子调控的非血红素铁催化烯烃不对称双羟化反应

Scheme 6. Nonheme iron-catalyzed asymmetric cis-dihydroxy- lation by modulating the counterions of the ferrous complex

图式7. 含手性羧酸配体的双核三价锰配合物催化不对称双羟化反应

Scheme 7. Asymmetric cis-dihydroxylation with a dinuclear Mn(III) complex containing chiral carboxylato ligands

图式8. 单核锰配合物催化以过硫酸氢钾制剂为氧源的烯烃不对称双羟化反应

Scheme 8. Mononuclear manganese-catalyzed asymmetric cis- dihydroxylation with oxone

图式9. 单核锰配合物催化以H2O2为氧化剂的烯烃不对称双羟化反应

Scheme 9. Mononuclear manganese-catalyzed asymmetric cis- dihydroxylation with H2O2

图式10. 单核锰配合物催化以KHSO5为氧化剂的烯烃不对称双羟化反应

Scheme 10. Mononuclear manganese-catalyzed asymmetric cis-dihydroxylation with KHSO5

图6. MnIII(H2O)(OOH)经水分子辅助路径生成HO—MnV=O的DFT吉布斯能垒计算

Figure 6. DFT-computed Gibbs energy profiles (in kcal mol−1) for water-assisted formation of HO—MnV=O from MnIII(H2O)- (OOH)

图式11. 单核非血红素锰催化烯烃不对称双羟化的可能反应机理

Scheme 11. Mechanistic proposal for asymmetric cis-dihydroxylation catalyzed by mononuclear nonheme Mn complex

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