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Issue 23, 2018
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Synthesis and applications of highly functionalized 1-halo-3-substituted bicyclo[1.1.1]pentanes

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Abstract

Bicyclo[1.1.1]pentanes (BCPs) are important bioisosteres of 1,4-disubstituted arenes, tert-butyl and acetylenic groups that can impart physicochemical benefits on drug candidates. Here we describe the synthesis of BCPs bearing carbon and halogen substituents under exceptionally mild reaction conditions, via triethylborane-initiated atom-transfer radical addition ring-opening of tricyclo[1.1.1.01,3]pentane (TCP) with alkyl halides. This chemistry displays broad substrate scope and functional group tolerance, enabling application to BCP analogues of biologically-relevant targets such as peptides, nucleosides, and pharmaceuticals. The BCP halide products can be converted to the parent phenyl/tert-butyl surrogates through triethylborane-promoted dehalogenation, or to other derivatives including carbonyls, alcohols, and heterocycles.

Graphical abstract: Synthesis and applications of highly functionalized 1-halo-3-substituted bicyclo[1.1.1]pentanes

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Publication details

The article was received on 23 Mar 2018, accepted on 20 May 2018 and first published on 21 May 2018


Article type: Edge Article
DOI: 10.1039/C8SC01355A
Citation: Chem. Sci., 2018,9, 5295-5300
  • Open access: Creative Commons BY license
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    Synthesis and applications of highly functionalized 1-halo-3-substituted bicyclo[1.1.1]pentanes

    D. F. J. Caputo, C. Arroniz, A. B. Dürr, J. J. Mousseau, A. F. Stepan, S. J. Mansfield and E. A. Anderson, Chem. Sci., 2018, 9, 5295
    DOI: 10.1039/C8SC01355A

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