cs7b00038_si_001.pdf (16.65 MB)
Remote C6-Selective Ruthenium-Catalyzed C–H Alkylation of Indole Derivatives via σ‑Activation
journal contribution
posted on 2017-03-06, 00:00 authored by Jamie
A. Leitch, Claire L. McMullin, Mary F. Mahon, Yunas Bhonoah, Christopher G. FrostThe
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.