非血红素锰配合物催化的缺电子烯烃仿生不对称顺式羟基叠氮化反应

doi:10.1016/S1872-2067(26)65117-0

摘要/Abstract

摘要：

β-叠氮基醇及其衍生的邻位羟基叠氮化物是合成生物活性分子、药物前体以及点击化学相关功能材料的重要中间体, 尤其在抗肿瘤药物紫杉醇的合成中发挥关键作用. 然而, 目前尚缺乏能够一步实现烯烃区域选择性及对映选择性顺式羟基叠氮化的高效化学催化方法. 已有策略多采用不对称环氧化后再经开环的两步路线, 或依赖底物范围受限的酶催化途径.
近年来, 非血红素手性双氨基双吡啶甲基锰配合物因其在仿生氧化催化中的优异表现而备受关注, 能够介导C=C基团与过氧化氢(H₂O₂)的各种高度对映选择性转化, 如环氧化、顺-1,2-二羟基化和顺-1,2-羟基酰氧基化. 基于此, 本研究探索了该类锰配合物在对缺电子烯烃的直接顺式羟基叠氮化反应中的应用. 实验结果表明, 以一系列非血红素锰配合物为催化剂、H₂O₂为末端氧化剂、叠氮化三甲基硅烷为叠氮源, α,β-不饱和羰基化合物可顺利转化为相应的邻位顺羟基叠氮化物, 对映选择性高达96% ee, 且表现出良好的区域选择性. 反应过程中, 目标产物与环氧化副产物存在竞争生成关系. 通过增大催化剂骨架的空间位阻或增强其给电子能力, 可有效促进叠氮基回弹路径、抑制环氧闭环副反应, 从而提升目标产物的选择性.机理研究表明, 反应可能经由活性物种(N₃)Mnᵛ=O对碳碳双键的亲电进攻启动, 生成由苄位共轭效应稳定化的缺电子中间体; 该中间体随后经历区域及立体选择性的叠氮基回弹, 最终形成顺式加成产物. 这一历程与Rieske双加氧酶催化烯烃顺式双羟基化的机制在概念上高度一致.
本研究首次实现了非酶催化条件下烯烃的高对映选择性顺式羟基叠氮化反应, 揭示了非血红素锰配合物在过氧化氢氧化体系中一种全新的催化反应模式, 深化了对仿生金属氧活性物种亲电进攻与叠氮转移行为的认识. 该催化策略为β-叠氮基醇类化合物的简洁合成提供了有效手段, 在精细化工及药物化学领域具有潜在应用价值.

关键词: 不对称催化, 叠氮醇, 仿生化学, 过氧化氢, 顺位添加, 锰, 机理

Abstract:

Previously, chiral bis-amino-bis-pyridylmethyl and structurally related Mn complexes have been reported to mediate a variety of highly enantioselective biomimetic oxidative transformations of C=C groups with hydrogen peroxide, such as epoxidations, syn-1,2-dihydroxylations, and syn-1,2-hydroxy acyloxylations. Herein, we present one more facet of their versatile catalytic reactivity which enables the enantioselective conversion of olefinic substrates to the corresponding vicinal syn-hydroxy azides in up to 96% ee. The data collected here provide evidence in favor of the direct regio- and enantioselective vicinal syn-hydroxyazidation of the substrate, using H₂O₂ as terminal oxidant and TMSN₃ as an azide source. Such reactivity is conceptually similar to that of Rieske dioxygenases, capable of adding two cis-substituents to the C=C group in a syn-selective fashion. The bioinspired catalyst systems discussed herein provide facile access to a variety of enantiomerically enriched 1,2,3-trifunctionalized compounds, featuring both syn and anti 2,3-hydroxy azide moieties.

Key words: Asymmetric catalysis, Azidoalcohols, Biomimetic chemistry, Hydrogen peroxide, Syn-addition, Manganese, Mechanism

Vladimir I. Kurganskii, Dmitry P. Lubov, Alexander G. Medvedev, 王瑞虎, Konstantin P. Bryliakov. 非血红素锰配合物催化的缺电子烯烃仿生不对称顺式羟基叠氮化反应[J]. 催化学报, 2026, 88: 468-477.

Vladimir I. Kurganskii, Dmitry P. Lubov, Alexander G. Medvedev, Ruihu Wang, Konstantin P. Bryliakov. Bioinspired asymmetric syn-hydroxyazidation of electron-deficient olefins in the presence of nonheme Mn complexes[J]. Chinese Journal of Catalysis, 2026, 88: 468-477.

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https://www.cjcatal.com/CN/Y2026/V88/I9/468

图/表 5

Fig. 1. Time profiles of chalcone oxidation with H2O2 (2.3 equiv.) in HFIP:CH2Cl2 (2:1 v/v) in the presence of (S,S)-10 (1 mol%) and TMSN3 (2 equiv.) at ?20 °C. Relative concentrations: substrate (11a) black, epoxide (12a) blue, hydroxy azide (13a) olive. Enantiomeric excess: epoxide (ee of 12a) red, hydroxy azide (ee of 13a) orange.

Fig. 2. X-ray molecular crystal structure of the hydroxyl azide 13b. Ellipsoids are drawn at the 50% probability level. C gray, O red, H light gray.

Scheme 1. Proposed mechanisms of 2,3-hydroxy acyloxylation (top, cf. Ref. [28]) and 2,3-hydroxy azidation (bottom).

Fig. 3. Hammett plots of Log{(100+ee)/(100−ee)} vs. σ+p for the hydroxyazidation of p-substituted chalcones by the systems 8/TMSN3/H2O2 (A) and 10/ TMSN3/H2O2 (B).

Scheme 2. Examples of semi-preparative syntheses of chiral syn (A) and anti (B) 2-hydroxy-3-azides using bioinspired Mn complexes as catalysts.

参考文献

[1]	J. Hamilton-Miller, W. Brumfitt, Infection, 1974, 2, 82-94.
[2]	L. Sun, Y. Peng, W. Yu, Y. Zhang, L. Liang, C. Song, J. Hou, Y. Qiao, Q. Wang, J. Chen, M. Wu, D. Zhang, E. Li, Z. Han, Q. Zhao, X. Jin, B. Zhang, Z. Huang, J. Chai, J.-H. Wang, J. Chang, J. Med. Chem., 2020, 63, 8554-8566.
[3]	K. Klumpp, V. Lévêque, S. Le Pogam, H. Ma, W.-R. Jiang, H. Kang, C. Granycome, M. Singer, C. Laxton, J. Q. Hang, K. Sarma, D. B. Smith, D. Heindl, C. J. Hobbs, J. H. Merrett, J. Symons, N. Cammack, J. A. Martin, R. Devos, I. Nájera, J. Biol. Chem., 2006, 281, 3793-3799.
[4]	H. X. Ding, K. K. C. Liu, S. M. Sakya, A. C. Flick, C. J. O’Donnell, Bioorg. Med. Chem., 2013, 21, 2795-2825.
[5]	M. Meldal, C. W. Tornøe, Chem. Rev., 2008, 108, 2952-3015.
[6]	R. Li, D. J. Jansen, A. Datta, Org. Biomol. Chem., 2009, 7, 1921-1930.
[7]	P. Thirumurugan, D. Matosiuk, K. Jozwiak, Chem. Rev., 2013, 113, 4905-4979.
[8]	D.-M. Gou, Y. C. Liu, C. S. Chen, J. Org. Chem., 1993, 58, 1287-1289.
[9]	L. Thijs, J. J. M. Porskamp, A. A. W. M. van Loon, M. P. W. Derks, R. W. Feenstra, J. Legters, B. Zwanenburg, Tetrahedron, 1990, 46, 2611-2622.
[10]	H. Sugihara, K. Daikai, X.-L. Jin, H. Furuno, J. Inanaga, Tetrahedron Lett., 2002, 43, 2735-2739.
[11]	M. Lanier, M. Le Blanc, R. Pastor, Tetrahedron, 1996, 52, 14631-14640.
[12]	J.-F. Wu, N.-W. Wan, Y.-N. Li, Q.-P. Wang, B.-D. Cui, W.-Y. Han, Y.-Z. Chen, iScience, 2021, 24, 102883.
[13]	M. Wu, B. Wang, S. Wang, C. Xia, W. Sun, Org. Lett., 2009, 11, 3622-3625.
[14]	R. V. Ottenbacher, K. P. Bryliakov, E. P. Talsi, Adv. Synth. Catal., 2011, 353, 885-889.
[15]	O. Y. Lyakin, R. V. Ottenbacher, K. P. Bryliakov, E. P. Talsi, ACS Catal., 2012, 2, 1196-1202.
[16]	I. Garcia-Bosch, L. Gómez, A. Polo, X. Ribas, M. Costas, Adv. Synth. Catal., 2012, 354, 65-70.
[17]	D. Shen, B. Qiu, D. Xu, C. Miao, C. Xia, W. Sun, Org. Lett., 2016, 18, 372-375.
[18]	R. V. Ottenbacher, D. G. Samsonenko, E. P. Talsi, K. P. Bryliakov, ACS Catal., 2016, 6, 979-988.
[19]	J. Du, C. Miao, C. Xia, Y.-M. Lee, W. Nam, W. Sun, ACS Catal., 2018, 8, 4528-4538.
[20]	R. V. Ottenbacher, V. I. Kurganskiy, E. P. Talsi, K. P. Bryliakov, Adv. Synth. Catal., 2021, 363, 2778-2782.
[21]	B. Wang, J. Lin, Q. Sun, C. Xia, W. Sun, ACS Catal., 2021, 11, 10964-10973.
[22]	J. Tian, J. Lin, J. Zhang, C. Xia, W. Sun, Adv. Synth. Catal., 2022, 364, 593-600.
[23]	A. G. Medvedev, D. A. Grishanov, A. A. Mikhaylov, A. V. Churakov, T. A. Tripol’skaya, R. V. Ottenbacher, K. P. Bryliakov, A. I. Shames, O. Lev, P. V. Prikhodchenko, Inorg. Chem., 2022, 61, 8193-8205.
[24]	C. Miao, B. Wang, Y. Wang, C. Xia, Y.-M. Lee, W. Nam, W. Sun, J. Am. Chem. Soc., 2016, 138, 936-943.
[25]	N. Choukairi Afailal, S.-C. Chan, M. Costas, Angew. Chem. Int. Ed., 2025, 64, e202504356.
[26]	R. V. Ottenbacher, A. A. Bryliakova, V. I. Kurganskii, P. V. Prikhodchenko, A. G. Medvedev, K. P. Bryliakov, Chem. Eur. J., 2023, 29, e202302772.
[27]	J. Chen, J. Zhang, Y. Sun, Y. Xu, Y. Yang, Y.-M. Lee, W. Ji, B. Wang, W. Nam, B. Wang, J. Am. Chem. Soc., 2023, 145, 27626-27638.
[28]	V. A. Sherstyuk, R. V. Ottenbacher, E. P. Talsi, K. P. Bryliakov, ACS Catal., 2024, 14, 498-507.
[29]	J. Chen, W. Song, Y.-M. Lee, W. Nam, B. Wang, Coord. Chem. Rev., 2023, 477, 214945.
[30]	K. P. Bryliakov, Coord. Chem. Rev., 2024, 508, 215793.
[31]	R. V. Ottenbacher, D. P. Lubov, D. G. Samsonenko, A. A. Nefedov, K. P. Bryliakov, J. Catal., 2024, 429, 115275.
[32]	R. V. Ottenbacher, D. G. Samsonenko, A. A. Nefedov, E. P. Talsi, K. P. Bryliakov, J. Catal., 2021, 399, 224-229.
[33]	R. V. Ottenbacher, D. G. Samsonenko, E. P. Talsi, K. P. Bryliakov, ACS Catal., 2014, 4, 1599-1606.
[34]	R. V. Ottenbacher, D. G. Samsonenko, A. A. Nefedov, K. P. Bryliakov, J. Catal., 2022, 415, 12-18
[35]	V. I. Kurganskiy, R. V. Ottenbacher, M. V. Shashkov, E. P. Talsi, D. G. Samsonenko, K. P. Bryliakov, Org. Lett., 2022, 24, 8764-8768.
[36]	The effect of azide source on the activation of bis-amino-bis-pyridylmethyl Mn complexes was scrutinized in Ref. [31]. Solid azide sources, such as NaN₃, Bu₄N₃ were shown [31] to be poor additives, deteriorating the catalytic conversions and entailing the need for unacceptably high excess of H₂O₂ (6-10 equiv.). An additional drawback is the difficulties with maintaining reaction mixture homogeneity when using NaN₃ or Bu₄N₃, which did not allow reducing the temperatures below -10…-20 °C. That is why solid azide sources were not used in this work.
[37]	V. I. Kurganskiy, A. A. Bryliakova, A. G. Medvedev, M. V. Shashkov, K. P. Bryliakov, ACS Catal., 2025, 15, 14938-14954.
[38]	R. V. Ottenbacher, D. G. Samsonenko, A. A. Bryliakova, A. A. Nefedov, K. P. Bryliakov, J. Catal., 2023, 425, 32-39.
[39]	W. Sun, Q. Sun, Acc. Chem. Res., 2019, 52, 2370-2381.
[40]	R. V. Ottenbacher, E. P. Talsi, K. P. Bryliakov, Chem. Rec., 2018, 18, 78-90.
[41]	N. Choukairi Afailal, M. Borrell, M. Cianfanelli, M. Costas, J. Am. Chem. Soc., 2024, 146, 240-249.
[42]	Log {(100+ee) /(100-ee)} plots vs. non-polar σ_p Hammett substituent parameters showed inferior correlations for both complexes.
[43]	In the case of catalyst 10, the point corresponding to p-Me-substituted chalcone (the least electron-deficient substrate in the series) dropped out of the common trend;the reason for this discrepancy is not clear at the moment.
[44]	Our preliminary data show that a similar deviation for p-Me substituted chalcone may be the case for Mn-catalyzed epoxidations of chalcones in the media of poly-β-fluorinated alcohols; this work is in progress.
[45]	The term Log {(100+ee)/(100-ee)}, equivalent to Log (k_major/k_minor), is proportional to the ΔΔG^≠ (where ΔΔG^≠ is the free energy difference between the two diastereomeric transition states leading to two enantiomeric products): Log {(100+ee)/(100-ee)} = -ΔΔG^≠/2.303RT, cf. Refs. [ 28] and [41].
[46]	A. A. Afon’kin, L. M. Kostrikin, A. E. Shumeiko, A. F. Popov, A. A. Matveev, V. N. Matvienko, A. F. Zabudkin, Russ. Chem. Bull., 2012, 61, 2149-2162.