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Bicyclobutanes As Unusual Building Blocks for Complexity Generation in Organic Synthesis

Overview
Journal Commun Chem
Publisher Springer Nature
Specialty Chemistry
Date 2023 Jan 25
PMID 36697911
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Abstract

Bicyclobutanes are among the most highly strained isolable organic compounds and their associated low activation barriers to reactivity make them intriguing building-blocks in organic chemistry. In recent years, numerous creative synthetic strategies exploiting their heightened reactivity have been presented and these discoveries have often gone hand-in-hand with the development of more practical routes for their synthesis. Their proclivity as strain-release reagents through their weak central C-C bond has been harnessed in a variety of addition, rearrangement and insertion reactions, providing rapid access to a rich tapestry of complex molecular scaffolds. This review will provide an overview of the different options available for bicyclobutane synthesis, the main classes of compounds that can be prepared from bicyclobutanes, and the associated modes of reactivity used.

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References
1.
McNamee R, Thompson A, Anderson E . Synthesis and Applications of Polysubstituted Bicyclo[1.1.0]butanes. J Am Chem Soc. 2021; 143(50):21246-21251. DOI: 10.1021/jacs.1c11244. View

2.
McNamee R, Haugland M, Nugent J, Chan R, Christensen K, Anderson E . Synthesis of 1,3-disubstituted bicyclo[1.1.0]butanes directed bridgehead functionalization. Chem Sci. 2021; 12(21):7480-7485. PMC: 8171340. DOI: 10.1039/d1sc01836a. View

3.
Kelly C, Colthart A, Constant B, Corning S, Dubois L, Genovese J . Enabling the synthesis of perfluoroalkyl bicyclobutanes via 1,3 γ-silyl elimination. Org Lett. 2011; 13(7):1646-9. DOI: 10.1021/ol200121f. View

4.
Yu X, Lubbesmeyer M, Studer A . Oligosilanes as Silyl Radical Precursors through Oxidative Si-Si Bond Cleavage Using Redox Catalysis. Angew Chem Int Ed Engl. 2020; 60(2):675-679. DOI: 10.1002/anie.202011738. View

5.
Silvi M, Aggarwal V . Radical Addition to Strained σ-Bonds Enables the Stereocontrolled Synthesis of Cyclobutyl Boronic Esters. J Am Chem Soc. 2019; 141(24):9511-9515. DOI: 10.1021/jacs.9b03653. View