Issue 23, 2018

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

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

Supplementary files

Article information

Article type
Edge Article
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
Creative Commons BY license

Chem. Sci., 2018,9, 5295-5300

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

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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