双环[1.1.0]丁烷(BCBs)的不对称开环与异构化研究进展
Research Progress on Asymmetric Ring-Opening and Isomerization of Bicyclo[1.1.0]Butanes (BCBs)
DOI: 10.12677/hjcet.2026.163019, PDF,    科研立项经费支持
作者: 白继峰, 程曼芳, 阿布都热西提·阿布力克木*：新疆师范大学化学化工学院，新疆 乌鲁木齐
关键词: 异构化；BCBs；双环[n.1.1]烷烃；Isomerization； BCBs； Bicyclo[n.1.1]Alkanes
摘要: 近几年，通过利用双环丁烷[1.1.0]释放环张力作为反应驱动力，继而与极性亲核试剂自由基等发生开环反应制备双环[n.1.1]烷烃的策略引起了材料化学、药物化学等领域学者的广泛关注。但是到目前为止还没有专门综述来探讨关于BCBs的不对称开环与异构化的研究进展。因此，本文按照催化体系的不同，对近几年关于BCBs的不对称开环与异构化的研究进展进行详细的综述。着重介绍了手性金属、手性Brønsted酸等不同的催化方式在不对称开环与异构化反应中的应用情况，并对未来发展做出了展望。
Abstract: In recent years, the strategy of utilizing the release of ring strain from bicyclo[1.1.0]butanes (BCBs) as a reaction driving force, followed by ring-opening reactions with polar nucleophiles, radicals, etc., to prepare bicyclo[n.1.1]alkanes has attracted widespread attention from researchers in fields such as materials chemistry and medicinal chemistry. However, to date, no dedicated review has addressed the research progress on the asymmetric ring-opening and isomerization of BCBs. Therefore, this review provides a detailed overview of recent advances in the asymmetric ring-opening and isomerization of BCBs, categorized by different catalytic systems. The applications of various catalytic approaches, including chiral metal catalysis and chiral Brønsted acid catalysis, in asymmetric ring-opening and isomerization reactions are highlighted, and future perspectives in this field are also discussed.
文章引用：白继峰, 程曼芳, 阿布都热西提·阿布力克木. 双环[1.1.0]丁烷(BCBs)的不对称开环与异构化研究进展[J]. 化学工程与技术, 2026, 16(3): 192-199. https://doi.org/10.12677/hjcet.2026.163019

参考文献

[1] Wiberg, K.B., Lampman, G.M., Ciula, R.P., Connor, D.S., Schertler, P. and Lavanish, J. (1965) Bicyclo[1.1.0]butane. Tetrahedron, 21, 2749-2769. [Google Scholar] [CrossRef] 
[2] Meiboom, S. and Snyder, L.C. (1971) Nuclear Magnetic Resonance Spectra in Liquid Crystals and Molecular Structure. Accounts of Chemical Research, 4, 81-87. [Google Scholar] [CrossRef] 
[3] Gassman, P.G., Greenlee, M.L., Dixon, D.A., Richtsmeier, S. and Gougoutas, J.Z. (1983) X-Ray and Theoretical Analysis of the Relationship between Substituent Steric Effects and the Structure of Bicyclo[1.1.0]butane. the Unexpected Flexibility of the Bicyclo[1.1.0]butane Skeleton. Journal of the American Chemical Society, 105, 5865-5874. [Google Scholar] [CrossRef] 
[4] Kelly, C.B., Milligan, J.A., Tilley, L.J. and Sodano, T.M. (2022) Bicyclobutanes: From Curiosities to Versatile Reagents and Covalent Warheads. Chemical Science, 13, 11721-11737. [Google Scholar] [CrossRef] [PubMed]
[5] de Meijere, A., Kozhushkov, S.I. and Schill, H. (2006) Three-Membered-Ring-Based Molecular Architectures. Chemical Reviews, 106, 4926-4996. [Google Scholar] [CrossRef] [PubMed]
[6] Walczak, M.A.A., Krainz, T. and Wipf, P. (2015) Ring-Strain-Enabled Reaction Discovery: New Heterocycles from Bicyclo[1.1.0]butanes. Accounts of Chemical Research, 48, 1149-1158. [Google Scholar] [CrossRef] [PubMed]
[7] Hui, C., Liu, Y., Jiang, M. and Wu, P. (2022) Cyclobutane-Containing Scaffolds in Bioactive Small Molecules. Trends in Chemistry, 4, 677-681. [Google Scholar] [CrossRef] 
[8] van der Kolk, M.R., Janssen, M.A.C.H., Rutjes, F.P.J.T. and Blanco-Ania, D. (2022) Cyclobutanes in Small-Molecule Drug Candidates. ChemMedChem, 17, e202200020. [Google Scholar] [CrossRef] [PubMed]
[9] Tsien, J., Hu, C., Merchant, R.R. and Qin, T. (2024) Three-Dimensional Saturated C(sp3)-Rich Bioisosteres for Benzene. Nature Reviews Chemistry, 8, 605-627. [Google Scholar] [CrossRef] [PubMed]
[10] Shire, B.R. and Anderson, E.A. (2023) Conquering the Synthesis and Functionalization of Bicyclo[1.1.1]pentanes. JACS Au, 3, 1539-1553. [Google Scholar] [CrossRef] [PubMed]
[11] Zhang, X., Smith, R.T., Le, C., McCarver, S.J., Shireman, B.T., Carruthers, N.I., et al. (2020) Copper-Mediated Synthesis of Drug-Like Bicyclopentanes. Nature, 580, 220-226. [Google Scholar] [CrossRef] [PubMed]
[12] Harmata, A.S., Spiller, T.E., Sowden, M.J. and Stephenson, C.R.J. (2021) Photochemical Formal (4+2)-Cycloaddition of Imine-Substituted Bicyclo[1.1.1]pentanes and Alkenes. Journal of the American Chemical Society, 143, 21223-21228. [Google Scholar] [CrossRef] [PubMed]
[13] Frank, N., Nugent, J., Shire, B.R., Pickford, H.D., Rabe, P., Sterling, A.J., et al. (2022) Synthesis of Meta-Substituted Arene Bioisosteres from [3.1.1]propellane. Nature, 611, 721-726. [Google Scholar] [CrossRef] [PubMed]
[14] Yu, T., Yang, J., Wang, Z., Ding, Z., Xu, M., Wen, J., et al. (2023) Selective [2σ+2σ] Cycloaddition Enabled by Boronyl Radical Catalysis: Synthesis of Highly Substituted Bicyclo[3.1.1]heptanes. Journal of the American Chemical Society, 145, 4304-4310. [Google Scholar] [CrossRef] [PubMed]
[15] Wen, K., Peng, Y. and Zeng, X. (2020) Advances in the Catalytic Asymmetric Synthesis of Quaternary Carbon Containing Cyclobutanes. Organic Chemistry Frontiers, 7, 2576-2597. [Google Scholar] [CrossRef] 
[16] Hancock, E.N., Wahl, J.M. and Brown, M.K. (2019) Recent Advances in the Synthesis Ofgem-Dimethylcyclobutane Natural Products. Natural Product Reports, 36, 1383-1393. [Google Scholar] [CrossRef] [PubMed]
[17] Xu, H., Zhang, W., Shu, D., Werness, J.B. and Tang, W. (2008) Synthesis of Cyclobutenes by Highly Selective Transition-Metal-Catalyzed Ring Expansion of Cyclopropanes. Angewandte Chemie International Edition, 47, 8933-8936. [Google Scholar] [CrossRef] [PubMed]
[18] Masarwa, A., Fürstner, A. and Marek, I. (2009) Metal-Catalyzed Rearrangement of Enantiomerically Pure Alkylidenecyclopropane Derivatives as a New Access to Cyclobutenes Possessing Quaternary Stereocenters. Chemical Communications, 2009, 5760-5762. [Google Scholar] [CrossRef] [PubMed]
[19] Odabachian, Y. and Gagosz, F. (2009) Cyclobutenes as Isolable Intermediates in the Gold(I)-Catalysed Cycloisomerisation of 1,8-Enynes. Advanced Synthesis & Catalysis, 351, 379-386. [Google Scholar] [CrossRef] 
[20] López-Carrillo, V. and Echavarren, A.M. (2010) Gold(I)-Catalyzed Intermolecular [2+2] Cycloaddition of Alkynes with Alkenes. Journal of the American Chemical Society, 132, 9292-9294. [Google Scholar] [CrossRef] [PubMed]
[21] Frébault, F., Luparia, M., Oliveira, M.T., Goddard, R. and Maulide, N. (2010) A Versatile and Stereoselective Synthesis of Functionalized Cyclobutenes. Angewandte Chemie International Edition, 49, 5672-5676. [Google Scholar] [CrossRef] [PubMed]
[22] Schotes, C. and Mezzetti, A. (2011) Enantioselective Ficini Reaction: Ruthenium/PNNP-Catalyzed [2+2] Cycloaddition of Ynamides with Cyclic Enones. Angewandte Chemie International Edition, 50, 3072-3074. [Google Scholar] [CrossRef] [PubMed]
[23] Niyomchon, S., Audisio, D., Luparia, M. and Maulide, N. (2013) Regio-and Enantioselective Cyclobutene Allylations. Organic Letters, 15, 2318-2321. [Google Scholar] [CrossRef] [PubMed]
[24] Maturi, M.M. and Bach, T. (2014) Enantioselective Catalysis of the Intermolecular [2+2] Photocycloaddition between 2-Pyridones and Acetylenedicarboxylates. Angewandte Chemie International Edition, 53, 7661-7664. [Google Scholar] [CrossRef] [PubMed]
[25] Leonori, D. and Aggarwal, V.K. (2014) Lithiation-Borylation Methodology and Its Application in Synthesis. Accounts of Chemical Research, 47, 3174-3183. [Google Scholar] [CrossRef] [PubMed]
[26] Fawcett, A., Biberger, T. and Aggarwal, V.K. (2019) Carbopalladation of C-C σ-Bonds Enabled by Strained Boronate Complexes. Nature Chemistry, 11, 117-122. [Google Scholar] [CrossRef] [PubMed]
[27] Tyler, J.L. and Aggarwal, V.K. (2023) Synthesis and Applications of Bicyclo[1.1.0]butyl and Azabicyclo[1.1.0]butyl Organometallics. Chemistry—A European Journal, 29, e202300008. [Google Scholar] [CrossRef] [PubMed]
[28] Shen, H., Popescu, M.V., Wang, Z., de Lescure, L., Noble, A., Paton, R.S., et al. (2023) Iridium-Catalyzed Asymmetric Difunctionalization of C-C σ-Bonds Enabled by Ring-Strained Boronate Complexes. Journal of the American Chemical Society, 145, 16508-16516. [Google Scholar] [CrossRef] [PubMed]
[29] Sun, Y.W., Zhao, J.H., Yan, X.Y., et al. (2024) Asymmetric Synthesis of Atropisomers Featuring Cyclobutane Boronic Esters Facilitated by Ring-Strained Bate Complexes. Nature Communications, 15, Article No. 10810. [Google Scholar] [CrossRef] [PubMed]
[30] Zhang, H., Liang, W.J., Xiao, J.A., et al. (2024) Palladium-Catalyzed Allylic Amination of Vinyl Bicyclo[1.1.0]butanes: A Strain Release Approach toward Alkylidenecyclobutanes. Green Synthesis and Catalysis, 1-5. [Google Scholar] [CrossRef] 
[31] Shi, F., Frank, N., Leutzsch, M., Zhu, C., Tsuji, N. and List, B. (2026) Catalytic Asymmetric Activation of Bicyclobutanes. Nature Synthesis, 5, 527-533. [Google Scholar] [CrossRef] 
[32] Lin, S.L., Chen, Y.H., Liu, H.H., et al. (2023) Enantioselective Synthesis of Chiral Cyclobutenes Enabled by Brønsted Acid-Catalyzed Isomerization of BCBs. Journal of the American Chemical Society, 145, 21152-21158. [Google Scholar] [CrossRef] [PubMed]