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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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Supplementary files

Article information


Submitted
23 Mar 2018
Accepted
20 May 2018
First published
21 May 2018

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2018,9, 5295-5300
Article type
Edge Article

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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