ncomms14801.pdf (475.35 kB)
Regioselective synthesis of C3 alkylated and arylated benzothiophenes
journal contribution
posted on 2019-09-23, 14:30 authored by Harry J. Shrives, José A. Fernández-Salas, Christin Hedtke, Alexander P. Pulis, David J. ProcterBenzothiophenes 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. 14801-14801Author affiliation
/Organisation/COLLEGE OF SCIENCE AND ENGINEERING/Department of ChemistryVersion
- VoR (Version of Record)