ncomms14801.pdf (475.35 kB)
Download file

Regioselective synthesis of C3 alkylated and arylated benzothiophenes

Download (475.35 kB)
journal contribution
posted on 23.09.2019, 14:30 by Harry J. Shrives, José A. Fernández-Salas, Christin Hedtke, Alexander P. Pulis, David J. Procter
Benzothiophenes are heterocyclic constituents of important molecules relevant to society, including those with the potential to meet modern medical challenges. The construction of molecules would be vastly more efficient if carbon–hydrogen bonds, found in all organic molecules, can be directly converted into carbon–carbon bonds. In the case of elaborating benzothiophenes, functionalization of carbon–hydrogen bonds at carbon-number 3 (C3) is markedly more demanding than at C2 due to issues of regioselectivity (C3 versus C2), and the requirement of high temperatures, precious metals and the installation of superfluous directing groups. Herein, we demonstrate that synthetically unexplored but readily accessible benzothiophene S-oxides serve as novel precursors for C3-functionalized benzothiophenes. Employing an interrupted Pummerer reaction to capture and then deliver phenol and silane coupling partners, we have discovered a directing group-free method that delivers C3-arylated and -alkylated benzothiophenes with complete regioselectivity, under metal-free and mild conditions.

Funding

We thank EPSRC (Postdoctoral Fellowship to J.A.F.-S.; Established Career Fellowship to D.J.P.), The University of Manchester (Lectureship to A.P.P.; Studentship to H.J.S.) and Novartis (Studentship to H.J.S.) for their generous support.

History

Citation

Nature Communications, 2017, 8, pp. 14801-14801

Author affiliation

/Organisation/COLLEGE OF SCIENCE AND ENGINEERING/Department of Chemistry

Version

VoR (Version of Record)

Published in

Nature Communications

Publisher

Nature Research (part of Springer Nature)

eissn

2041-1723

Acceptance date

02/02/2017

Copyright date

2017

Available date

23/09/2019

Publisher version

https://www.nature.com/articles/ncomms14801

Notes

The X-ray crystallographic coordinates for 3a have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition number CCDC 1511568. This data can be obtained free of charge from the CCDC via www.ccdc.cam.ac.uk/data_request/cif. The authors declare that all other data supporting the findings of this study are available within the article and its Supplementary Information file. https://www.nature.com/articles/ncomms14801#MOESM2766

Language

en

Usage metrics

Categories

Licence

Exports