Oxidative functionalization of indoles is one of the
most widely
used approaches to exploit the synthetic utility of indoles. In continuation
of our research interest in the green oxidation of indoles, we further
explore the oxidation of indoles with oxone–halide and discover
that the protecting group on the nitrogen of indoles plays a decisive
role in controlling the pathways of indole oxidation with oxone–halide.
An electron-withdrawing group on the nitrogen of indoles (N-EWG) enables
C2 halogenation with stoichiometric halide, while C3 halogenation
could be selectively achieved by using stoichiometric halide without
dependence on the electronic property of the protecting group on the
indole nitrogen. Different from our previous results obtained by using
catalytic halide, these findings lead to the development of an environmentally
friendly, efficient, and mild protocol for access to 2- or 3-haloindoles
(chloro and bromo). As compared to the previous synthetic methods
for 2-/3-haloindoles, our method exploits the in situ-generated reactive
halogenating species from oxone–halide for halogenation of
indoles and thus eliminates the use of stoichiometric halogenating
agents and the production of toxic and hazardous organic byproducts
derived from oxidants.
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