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. 2023 Jan 12;6:9. doi: 10.1038/s42004-022-00811-3

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — A Overview of the different synthetic approaches to bicyclobutanes categorised by the bonds formed. B The landmark first synthesis of a bicyclobutane derivative by Wiberg and Ciula. C The most commonly used synthetic routes to bicyclobutanes, highlighting the derivatives that can be formed with each route with a focus on the substitution pattern and functional groups that can be incorporated. HMDS bis(trimethylsilyl)amide, TMS trimethylsilyl, Ms methane sulfonyl, tol tolyl, pin pinacol, Ts para-toluene sulfonyl, NTTL N-1,8-naphthaloyl-(S)-tert-leucine; Boc tert-butoxycarbonyl, EWG electron-withdrawing group, LG leaving group, Nu nucleophile, El electrophile.