Abstract
The site-selective functionalization of an indole template offers exciting possibilities for the derivatization of molecules with useful biological properties. Herein, we report the remote C6-selective C-H alkylation of indole derivatives enabled by dual cyclometalation/redox ruthenium catalysis. Remote alkylation was achieved using N-pyrimidinyl indoles with an ancillary ester directing group at the C3 position. This ancillary directing group proved pivotal to reactivity at C6, with yields up to 92% achieved. A one-pot procedure to install this directing group followed by remote C6 functionalization has also been reported; both processes are shown to proceed via ruthenium redox catalysis. Computationally calculated Fukui indices elucidated that the C6 position was the most reactive vacant C-H site toward potential functionalization. When this investigation was coupled with deuterium incorporation studies, a C2-cyclometalation/remote σ-activation pathway was deduced.
Original language | English |
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Pages (from-to) | 2616-2623 |
Number of pages | 8 |
Journal | ACS Catalysis |
Volume | 7 |
Issue number | 4 |
Early online date | 6 Mar 2017 |
DOIs | |
Publication status | Published - 7 Apr 2017 |
Keywords
- heteroaromatics
- homogeneous catalysis
- indole
- remote functionalization
- ruthenium
ASJC Scopus subject areas
- Catalysis
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Equipment
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Balena High Performance Computing (HPC) System
Facility/equipment: Equipment
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High Performance Computing (HPC) Facility
Chapman, S. (Manager)
University of BathFacility/equipment: Facility