Yin Li, Xiao‐Bin Liu, Vadym Sham, Ivan Logvinenko, Jiang‐Hao Xue, Jun‐Yunzi Wu, Jia‐Luo Fu, Shuang Lin, Yuan Liu, Qingjiang Li, Pavel K. Mykhailiuk and Honggen Wang

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202422899

Three-dimensional saturated C(sp3)-rich bioisosteres for benzene

Jet Tsien, Chao Hu, Rohan R. Merchant and Tian Qin

Nat Rev Chem, 2024, 8, 605
DOI: 10.1038/s41570-024-00623-0

3-Substituted 6-Azabicyclo[3.1.1]heptanes: Nonclassical Piperidine Isosteres for Drug Discovery

Anton V. Chernykh, Bohdan V. Vashchenko, Svitlana V. Shishkina, Dmytro M. Volochnyuk and Oleksandr O. Grygorenko

J. Org. Chem., 2024, 89, 10440
DOI: 10.1021/acs.joc.4c00326

Light‐Driven Synthesis and Functionalization of Bicycloalkanes, Cubanes and Related Bioisosteres

Sara Cuadros, Julien Paut, Elsa Anselmi, Guillaume Dagousset, Emmanuel Magnier and Luca Dell'Amico

Angew Chem Int Ed, 2024, 63
DOI: 10.1002/anie.202317333

2‐Oxabicyclo[2.1.1]hexanes: Synthesis, Properties, and Validation as Bioisosteres of ortho‐ and meta‐Benzenes

Vadym V. Levterov, Yaroslav Panasiuk, Oleh Shablykin, Oleksandr Stashkevych, Kateryna Sahun, Artur Rassokhin, Iryna Sadkova, Dmytro Lesyk, Anna Anisiforova, Yuliia Holota, Petro Borysko, Iryna Bodenchuk, Nataliya M. Voloshchuk and Pavel K. Mykhailiuk

Angew Chem Int Ed, 2024, 63
DOI: 10.1002/anie.202319831

From Flat to 3D: Replacing Phenyl Rings with Saturated Bridged Bicyclic Mimetics to Mitigate Bioactivation and Optimize ADME Properties and Oral Bioavailability in Reverse Amide Orientation

Murugaiah A. M. Subbaiah, Shruti Surendran, Gaurav Saini, Lavanya Billava Ramappa, Sivashankaran Raju, Joyson Nandha, Himangshu Bhowmik, Enugurthi Krishna, Sushmita Janrao, Vijay Kumar, Shruti Shikha Choubey, Joothipriya Subramanian, Bhuvaneshwaran Anandamoorthy, Sukanta Kumar Sahoo, Raghavendra Veerapuram, Korlepara Vamsi Krishna, Manohar Yelleswarapu, Yogesh Kumar Gupta, Muthalagu Vetrichelvan, Anuradha Gupta, Salil Desai, Thanga Mariappan, Arvind Mathur and Prakash Ramaseshan Vachaspati

J. Med. Chem., 2026, 69, 8215
DOI: 10.1021/acs.jmedchem.5c03656

Stellane at the Forefront: Derivatization and Reactivity Studies of a Promising Saturated Bioisostere of ortho-Substituted Benzenes

Oleh K. Smyrnov, Kostiantyn P. Melnykov, Olexandr Ye. Pashenko, Dmytro M. Volochnyuk and Serhiy V. Ryabukhin

Org. Lett., 2024, 26, 4808
DOI: 10.1021/acs.orglett.4c01645

Bicyclo[2.1.1]hexanes via Intramolecular Formal (3+2)‐Cycloaddition

Alexander S. Harmata, Elene Tatunashvili, Abigail Chang, Tao Wang and Corey R. J. Stephenson

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202413695

Lewis Acid Catalyzed Cycloaddition Reaction of Bicyclo[1.1.0]butanes

Hui Yang, Jie Chen and Ling Zhou

Synlett, 2025, 36, 788
DOI: 10.1055/a-2456-9789

Catalytic Intermolecular Asymmetric [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes: Practical Synthesis of Enantioenriched Highly Substituted Bicyclo[2.1.1]hexanes

Ying-Jie Li, Zhi-Long Wu, Qiang-Shuai Gu, Tingting Fan, Ming-Hao Duan, Lihong Wu, Yu-Tao Wang, Ji-Peng Wu, Fang-Lei Fu, Fan Sang, Ai-Ting Peng, Yuyang Jiang, Xin-Yuan Liu and Jin-Shun Lin

J. Am. Chem. Soc., 2024, 146, 34427
DOI: 10.1021/jacs.4c10968

Smallest Bicycles in Medicinal Chemistry: Where Are We Now?

Vladimir Kubyshkin and Pavel K. Mykhailiuk

Chem. Rev., 2026, 126, 3829
DOI: 10.1021/acs.chemrev.5c00779

Recent Progress in Accessing Multi-functionalized Caged Hydrocarbons: En Route to Highly Functionalized Saturated (Bio)isosteres of Benzene Rings

Shota Nagasawa and Yoshiharu Iwabuchi

Synthesis, 2025, 57, 1153
DOI: 10.1055/a-2360-8218

Salen-Ti-Catalyzed Formal [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes with Alkenes

Enhui Zhou, Yihe Zhu, Lu Qiu, Fangyi Jin, Yaning Han, Erjun Hao and Lei Shi

Synthesis, 2026
DOI: 10.1055/a-2837-4073

σ-Bond insertion reactions of two strained diradicaloids

Arismel Tena Meza, Christina A. Rivera, Huiling Shao, Andrew V. Kelleghan, K. N. Houk and Neil K. Garg

Nature, 2025, 640, 683
DOI: 10.1038/s41586-025-08745-1

Enantioselective [2π + 2σ] cycloaddition of bicyclobutanes with imines: An efficient approach to chiral 2-aza-bicyclo[2.1.1]hexanes

Xuan-Ge Zhang, Jun-Jia Chen, Zi-Yang Zhou, Jia-Xin Li and Qi-Lin Zhou

Chem Catalysis, 2025, 5, 101295
DOI: 10.1016/j.checat.2025.101295

Simultaneous Activation of Bicyclobutanes and Indolyl Alcohols with HFIP: Access to Indole‐Fused Bicyclo[3.1.1]Heptanes

Shiksha Deswal, Rohan Chandra Das, Deeptanu Sarkar and Akkattu T. Biju

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202501655

Spiro[3.3]heptane as a Saturated Benzene Bioisostere**

Kateryna Prysiazhniuk, Oleksandr P. Datsenko, Oleksandr Polishchuk, Stanislav Shulha, Oleh Shablykin, Yelyzaveta Nikandrova, Kateryna Horbatok, Iryna Bodenchuk, Petro Borysko, Dmytro Shepilov, Iryna Pishel, Vladimir Kubyshkin and Pavel K. Mykhailiuk

Angew Chem Int Ed, 2024, 63
DOI: 10.1002/anie.202316557

Lewis Acid-Catalyzed Asymmetric [2σ + 2π] Cycloaddition Reactions of Bicyclo[1.1.0]butanes and Vinyl Azido/Diazo Compounds

Haosong Ren, Zhongren Lin, Tianxiang Li, Zhenyue Li, Xinhong Yu and Jun Zheng

ACS Catal., 2025, 15, 4634
DOI: 10.1021/acscatal.5c00303

Simultaneous Activation of Bicyclobutanes and Indolyl Alcohols with HFIP: Access to Indole‐Fused Bicyclo[3.1.1]Heptanes

Shiksha Deswal, Rohan Chandra Das, Deeptanu Sarkar and Akkattu T. Biju

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202501655

Light‐Enabled [2σ + 2π] Cycloadditions of Bicyclo[1.1.0]butanes and Alkenes by Ti‐Salen Photocatalysis

Jinping Xing, Dexia Li, Tianxiang Li, Yang Xu, Haosong Ren and Jun Zheng

ChemistryEurope, 2026, 4
DOI: 10.1002/ceur.202500139

Sc(OTf)3‐Catalyzed Ring‐Opening Reactions of Donor‐Acceptor Cyclopropanes/Bicyclo[1.1.0]butanes: Access to 3‐Substituted Chromenones, Cyclopenta[b]chromenones and 2‐Aminobicyclo[2.1.1]hexanes

Poonam Rani and Sampak Samanta

Adv Synth Catal, 2025, 367
DOI: 10.1002/adsc.202500132

Eu(OTf)3‐Catalyzed Formal Dipolar [4π+2σ] Cycloaddition of Bicyclo‐[1.1.0]butanes with Nitrones: Access to Polysubstituted 2‐Oxa‐3‐azabicyclo[3.1.1]heptanes

Jian Zhang, Jia‐Yi Su, Hanliang Zheng, Hao Li and Wei‐Ping Deng

Angew Chem Int Ed, 2024, 63
DOI: 10.1002/anie.202318476

Access to 2-Oxabicyclo[2.1.1]hexanes and their use in Scaffold Hopping

Olivier Lorthioir, Niall Anderson, Scott Boyd, Luca Carlino, Paul Davey, William Hodds, Megan Howard, Marika Lindhagen, Katie Proctor, Okky Dwichandra Putra, Theo Smith, Oliver Turner, Alfie Woodhouse and Millie Woodward

Org. Lett., 2024, 26, 9179
DOI: 10.1021/acs.orglett.4c02221

(Bio)isosteres of ortho- and meta-substituted benzenes

H Erik Diepers and Johannes C L Walker

Beilstein J. Org. Chem., 2024, 20, 859
DOI: 10.3762/bjoc.20.78

Recent Progress in (3+3) Cycloadditions of Bicyclobutanes to Access Bicyclo[3.1.1]heptane Derivatives

Jian-Jun Feng

Synlett, 2025, 36, 621
DOI: 10.1055/a-2406-3243

Assessing the rigidity of cubanes and bicyclo(1.1.1)pentanes as benzene bioisosteres

Graham Pattison

Bioorganic & Medicinal Chemistry, 2024, 102, 117652
DOI: 10.1016/j.bmc.2024.117652

Bicyclo[2.1.1]hexanes via Intramolecular Formal (3+2)‐Cycloaddition

Alexander S. Harmata, Elene Tatunashvili, Abigail Chang, Tao Wang and Corey R. J. Stephenson

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202413695

Recent Advances in Catalytic Asymmetric Transformations of Bicyclobutane: A Versatile Building Block for Enantiopure Bioisosteric Molecules

Yejin Koo, Jinwook Jeong and Sungwoo Hong

ACS Catal., 2025, 15, 8078
DOI: 10.1021/acscatal.5c01900

Facile Synthesis of Housanes by an Unexpected Strategy

Yanyao Liu, Somanea Tranin, Yu-Che Chang, Evan B. Piper, Thomas Fessard, Ryan Van Hoveln, Christophe Salome and M. Kevin Brown

J. Am. Chem. Soc., 2025, 147, 6318
DOI: 10.1021/jacs.4c13298

Lewis Acid-Catalyzed 1,3-Dipolar Cycloaddition of Bicyclobutanes with Isatogens: Access to Tetracyclic 2-Oxa-3-azabicyclo[3.1.1]heptanes

Shiksha Deswal, Rohan Chandra Das, Deeptanu Sarkar and Akkattu T. Biju

JACS Au, 2025, 5, 136
DOI: 10.1021/jacsau.4c00839

Calcium(II)‐Catalyzed Synthesis of Sulfoximinocyclopentenones

Xiangmeng Chen, Christophe Bour, Emilie Kolodziej, Régis Guillot, Nicolas S. George, Aurélien Alix and Vincent Gandon

Adv Synth Catal, 2025, 367
DOI: 10.1002/adsc.202401085

2‐Oxabicyclo[2.1.1]hexanes: Synthesis, Properties, and Validation as Bioisosteres of ortho‐ and meta‐Benzenes

Vadym V. Levterov, Yaroslav Panasiuk, Oleh Shablykin, Oleksandr Stashkevych, Kateryna Sahun, Artur Rassokhin, Iryna Sadkova, Dmytro Lesyk, Anna Anisiforova, Yuliia Holota, Petro Borysko, Iryna Bodenchuk, Nataliya M. Voloshchuk and Pavel K. Mykhailiuk

Angewandte Chemie, 2024, 136
DOI: 10.1002/ange.202319831

Saturated F2‐Rings from Alkenes

Yin Li, Xiao‐Bin Liu, Vadym Sham, Ivan Logvinenko, Jiang‐Hao Xue, Jun‐Yunzi Wu, Jia‐Luo Fu, Shuang Lin, Yuan Liu, Qingjiang Li, Pavel K. Mykhailiuk and Honggen Wang

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202422899

Lewis Acid Catalyzed Cycloaddition of Bicyclobutanes with Ynamides for the Synthesis of Polysubstituted 2‐Amino‐bicyclo[2.1.1]hexenes

Qian‐Qian Hu, Liu‐Yang Wang, Xing‐Hao Chen, Ze‐Xiang Geng, Jie Chen and Ling Zhou

Angew Chem Int Ed, 2024, 63
DOI: 10.1002/anie.202405781

Catalytic Asymmetric Synthesis of Chiral Caged Hydrocarbons as Arenes Bioisosteres

Xue‐Chun Yang, Ji‐Jie Wang, Yuanjiu Xiao and Jian‐Jun Feng

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202505803

Eu(OTf)3‐Catalyzed Formal Dipolar [4π+2σ] Cycloaddition of Bicyclo‐[1.1.0]butanes with Nitrones: Access to Polysubstituted 2‐Oxa‐3‐azabicyclo[3.1.1]heptanes

Jian Zhang, Jia‐Yi Su, Hanliang Zheng, Hao Li and Wei‐Ping Deng

Angewandte Chemie, 2024, 136
DOI: 10.1002/ange.202318476

Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity

Pablo Garrido-García, Irene Quirós, Paula Milán-Rois, Silvia Ortega-Gutiérrez, Mar Martín-Fontecha, Luis A. Campos, Álvaro Somoza, Israel Fernández, Thomas Rigotti and Mariola Tortosa

Nat. Chem., 2025, 17, 734
DOI: 10.1038/s41557-025-01746-7

Synthesis of 2‐Substituted Bicyclo[2.1.1]Hexan‐1‐ols via SmI2‐Mediated Reductive Cyclization Reactions

Chih‐Wei Hsu, Chun‐Fu Wu, Yung‐Chi Lee and Woo‐Jin Yoo

Adv Synth Catal, 2024, 366, 4747
DOI: 10.1002/adsc.202400891

Asymmetric C–H Functionalization of Bicyclo[2.1.1]hexanes and Their 2-Oxa- and 2-Aza Derivatives via Rhodium Carbene Intermediates

Ziyi Chen, Duc Ly, Yuzuru Kanda, Vadym V. Levterov, Yaroslav Panasiuk, Pavel K. Mykhailiuk, Djamaladdin G. Musaev and Huw M. L. Davies

J. Am. Chem. Soc., 2026, 148, 2709
DOI: 10.1021/jacs.5c19070

Palladium-catalyzed enantioselective [2σ + 2π] cycloadditions of vinyl-carbonyl-bicyclo[1.1.0]butanes with arylidenemalononitriles

Tianzhu Qin and Weiwei Zi

Chinese Chemical Letters, 2026, 37, 111072
DOI: 10.1016/j.cclet.2025.111072

Spiro[3.3]heptane as a Saturated Benzene Bioisostere**

Kateryna Prysiazhniuk, Oleksandr P. Datsenko, Oleksandr Polishchuk, Stanislav Shulha, Oleh Shablykin, Yelyzaveta Nikandrova, Kateryna Horbatok, Iryna Bodenchuk, Petro Borysko, Dmytro Shepilov, Iryna Pishel, Vladimir Kubyshkin and Pavel K. Mykhailiuk

Angewandte Chemie, 2024, 136
DOI: 10.1002/ange.202316557

Synthesis of Borylated Carbocycles by [2 + 2]-Cycloadditions and Photo-Ene Reactions

Jarett M. Posz, Neetu Sharma, Paige A. Royalty, Yanyao Liu, Christophe Salome, Thomas C. Fessard and M. Kevin Brown

J. Am. Chem. Soc., 2024, 146, 10142
DOI: 10.1021/jacs.4c01557

Facile access to bicyclo[2.1.1]hexanes by Lewis acid-catalyzed formal cycloaddition between silyl enol ethers and bicyclo[1.1.0]butanes

Sai Hu, Yuming Pan, Dongshun Ni and Li Deng

Nat Commun, 2024, 15
DOI: 10.1038/s41467-024-50434-6

Iodine(I)‐Induced Skeletal Rearrangement of α‐Bicyclobutanyl Alcohols and Amines: A Universal Approach to 2‐Oxabicyclo[2.1.1]hexanes and 2‐Azabicyclo[2.1.1]hexanes

Yuchen Wang, Lin Zheng, Xin Liu, Chi Zhang, Yongjiu Li, Qingfu Li, Xingyu Zhang, Wei Lin and Chenguang Liu

Angew Chem Int Ed, 2026, 65
DOI: 10.1002/anie.202523632

Light‐Driven Synthesis and Functionalization of Bicycloalkanes, Cubanes and Related Bioisosteres

Sara Cuadros, Julien Paut, Elsa Anselmi, Guillaume Dagousset, Emmanuel Magnier and Luca Dell'Amico

Angewandte Chemie, 2024, 136
DOI: 10.1002/ange.202317333

Photoredox Activation of Donor‐Acceptor Cyclopropanes: Distonic Radical Cation Reactivity in [3+2] Cycloaddition Reactions

Subhashis Mondal, Saradindu Debnath, Rabindranath Lo and Soumitra Maity

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202419426

Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp3)–N coupling

Kang-Ning Yuan, Hongjun Zhuang, Jie Wei, Yu Shen, Hong-Qing Yao, Ming-Hong Li, Lin-Lin Xu and Ming Shang

Nat Commun, 2025, 16
DOI: 10.1038/s41467-024-54648-6

Discovery Process Chemistry: An Innovation Hub at the Interface of Academia, the Pharmaceutical Industry, and Contract Research Organizations

Matthew A. Horwitz

Synthesis, 2025, 57, 925
DOI: 10.1055/a-2380-6425

Modular Synthesis of Azidobicyclo[2.1.1]hexanes via (3 + 2) Annulation of α-Substituted Vinyl Azides and Bicyclo[1.1.0]butanes

Sai Hu, Yuhong Gao, Yuming Pan, Dongshun Ni and Li Deng

J. Org. Chem., 2024, 89, 15151
DOI: 10.1021/acs.joc.4c01920

Síntesis de bioisósteros 3D de arenos mediante métodos fotocatalíticos

Sara Cuadros Huertas

AnQuimRSEQ, 2026, 122, 63
DOI: 10.62534/rseq.aq.2113

Catalytic Asymmetric Synthesis of Chiral Caged Hydrocarbons as Arenes Bioisosteres

Xue‐Chun Yang, Ji‐Jie Wang, Yuanjiu Xiao and Jian‐Jun Feng

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202505803

Chemo‐, Diastereo‐, and Enantioselective (3+2) Cycloadditons of Bicyclobutanes with Enals Enabled by Synergistic Palladium and Organocatalysis

Feng Wu, Quanxin Peng, Yu‐Jie Li, Yuanjiu Xiao and Jian‐Jun Feng

Chin. J. Chem., 2026, 44, 241
DOI: 10.1002/cjoc.70355

Annulation of Hydroxyarenes and Derivatives with Bicyclo[1.1.0]butanes by Synergistic Combination of Metal Lewis Acid and Organic Acid

Qihang Guo, Dongshun Ni and Li Deng

JACS Au, 2025, 5, 5059
DOI: 10.1021/jacsau.5c00956

Pyridine-boryl radical-catalyzed [3π + 2σ] cycloaddition for the synthesis of pyridine isosteres

Yuan Liu, Shuang Lin, Zhengwei Ding, Yin Li, Ya-Jie Tang, Jiang-Hao Xue, Qingjiang Li, Pengfei Li and Honggen Wang

Chem, 2024, 10, 3699
DOI: 10.1016/j.chempr.2024.08.010

Photoredox Activation of Donor‐Acceptor Cyclopropanes: Distonic Radical Cation Reactivity in [3+2] Cycloaddition Reactions

Subhashis Mondal, Saradindu Debnath, Rabindranath Lo and Soumitra Maity

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202419426

Strain‐Enabled Radical‐Polar Crossover Annulation to Access Spiro‐, Fused‐, and Enantioenriched‐Aza/Oxa‐Bicyclo[3.1.1]Heptanes

Bhismalochan Ghorai, Buddhadeb Sahana and Durga Prasad Hari

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202506747

Regiospecific dearomative [2π + 2σ] photo-cycloaddition of polyfluoronaphthalenes with bicyclo[1.1.0]butanes via energy transfer catalysis

Sayan K. Jana, Anusha Biswas, Sanat Kumar Mahapatra, Lisa Roy and Biplab Maji

Cell Reports Physical Science, 2026, 103223
DOI: 10.1016/j.xcrp.2026.103223

Synthetic Strategies and Applications of Fluorine‐Containing Bridged Bicyclic Compounds

Simone Baldon, Luca Dell'Amico and Sara Cuadros

Eur J Org Chem, 2024, 27
DOI: 10.1002/ejoc.202400604

Intramolecular [2+2] Cycloadditions of α‐Heteroatom Substituted γ,δ‐Unsaturated Ketenes

Tzi‐Chi Liu, Zih‐Hao Lin and Woo‐Jin Yoo

Asian J Org Chem, 2024, 13
DOI: 10.1002/ajoc.202400302