Synthesis of Functionalized Methyl-Substituted Bicyclo[1.1.1]pentanes
DOI:
https://doi.org/10.17721/fujcV12I1P111-117Keywords:
Bicyclo[1.1.1]pentanes, BCP, photochemistry, flow chemistryAbstract
Synthesis of new functionalized methyl-substituted bicyclo[1.1.1]pentanes for medicinal chemistry is presented. All the products were obtained in multigram quantities with decent yields. The synthetic approaches reported are facile and scalable. We hope that this work will help process chemists at pharmaceutical companies with the preparation of bioactive bicyclo[1.1.1]pentanes suggested by medicinal chemists for clinical trials.
References
Shearer J, Castro J, Lawson A, MacCoss M, Taylor R. Rings in Clinical Trials and Drugs: Present and Future. Journal of Medicinal Chemistry 2022;65(13):8699-8712. https://doi.org/10.1021/acs.jmedchem.2c00473
Stepan A, Subramanyam C, Efremov I, Dutra J, O’Sullivan T, DiRico K, McDonald W, Won A, Dorff P, Nolan C, Becker S, Pustilnik L, Riddell D, Kauffman G, Kormos B, Zhang L, Lu Y, Capetta S, Green M, Karki K, Sibley E, Atchison K, Hallgren A, Oborski C, Robshaw A, Sneed B, O’Donnell C. Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor. Journal of Medicinal Chemistry 2012;55(7):3414-3424. https://doi.org/10.1021/jm300094u
Mykhailiuk P. Saturated bioisosteres of benzene: where to go next? Organic & Biomolecular Chemistry 2019;17(11):2839-2849. https://doi.org/10.1039/c8ob02812e
Locke G, Bernhard S, Senge M. Nonconjugated Hydrocarbons as Rigid‐Linear Motifs: Isosteres for Material Sciences and Bioorganic and Medicinal Chemistry. Chemistry – A European Journal 2019;25(18):4590-4647. https://doi.org/10.1002/chem.201804225
Macreadie L, Idrees K, Smoljan C, Farha O. Expanding Linker Dimensionality in Metal‐organic Frameworks for sub‐Ångstrom Pore Control for Separation Applications. Angewandte Chemie International Edition 2023;62(28):e202304094. https://doi.org/10.1002/anie.202304094
Subbaiah M, Meanwell N. Bioisosteres of the Phenyl Ring: Recent Strategic Applications in Lead Optimization and Drug Design. Journal of Medicinal Chemistry 2021;64(19):14046-14128. https://doi.org/10.1021/acs.jmedchem.1c01215
Kanazawa J, Uchiyama M. Recent Advances in the Synthetic Chemistry of Bicyclo[1.1.1]pentane. Synlett 2018;30(01):1-11. https://doi.org/10.1055/s-0037-1610314
Ma X, Nhat Pham L. Selected Topics in the Syntheses of Bicyclo[1.1.1]Pentane (BCP) Analogues. Asian Journal of Organic Chemistry 2019;9(1):8-22. https://doi.org/10.1002/ajoc.201900589
He F, Xie S, Yao Y, Wu J. Recent advances in the applications of [1.1.1]propellane in organic synthesis. Chinese Chemical Letters 2020;31(12):3065-3072. https://doi.org/10.1016/j.cclet.2020.04.023
Anderson J, Measom N, Murphy J, Poole D. Bridge Functionalisation of Bicyclo[1.1.1]pentane Derivatives. Angewandte Chemie International Edition 2021;60(47):24754-24769. https://doi.org/10.1002/anie.202106352
Shire B, Anderson E. Conquering the Synthesis and Functionalization of Bicyclo[1.1.1]pentanes. JACS Au 2023;3(6):1539-1553. https://doi.org/10.1021/jacsau.3c00014
Bellotti P, Glorius F. Strain-Release Photocatalysis. Journal of the American Chemical Society 2023;145(38):20716-20732. https://doi.org/10.1021/jacs.3c08206
Kaszynski P, McMurdie N, Michl J. Synthesis of doubly bridgehead substituted bicyclo[1.1.1]pentanes. Radical transformations of bridgehead halides and carboxylic acids. The Journal of Organic Chemistry 1991;56(1):307-316. https://doi.org/10.1021/jo00001a058
Caputo D, Arroniz C, Dürr A, Mousseau J, Stepan A, Mansfield S, Anderson E. Synthesis and applications of highly functionalized 1-halo-3-substituted bicyclo[1.1.1]pentanes. Chemical Science 2018;9(23):5295-5300. https://doi.org/10.1039/c8sc01355a
Wong M, Mousseau J, Mansfield S, Anderson E. Synthesis of Enantioenriched α-Chiral Bicyclo[1.1.1]pentanes. Organic Letters 2019;21(7):2408-2411. https://doi.org/10.1021/acs.orglett.9b00691
Pickford H, Nugent J, Owen B, Mousseau J, Smith R, Anderson E. Twofold Radical-Based Synthesis of N,C-Difunctionalized Bicyclo[1.1.1]pentanes. Journal of the American Chemical Society 2021;143(26):9729-9736. https://doi.org/10.1021/jacs.1c04180
Ripenko V, Sham V, Levchenko V, Holovchuk S, Vysochyn D, Klymov I, Kyslyi D, Veselovych S, Zhersh S, Dmytriv Y, Tolmachev A, Sadkova I, Pishel I, Horbatok K, Kosach V, Nikandrova Y, Mykhailiuk P. Light-enabled scalable synthesis of bicyclo[1.1.1]pentane halides and their functionalizations. Nature Synthesis 2024;3(12):1538-1549. https://doi.org/10.1038/s44160-024-00637-y
Downloads
Published
Issue
Section
License
Copyright (c) 2024 French-Ukrainian Journal of Chemistry
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
