Photoinduced, Copper-Catalyzed Alkylation of Amines: A Mechanistic Study of the Cross-Coupling of Carbazole with Alkyl Bromides

We
have recently reported that a variety of couplings of nitrogen,
sulfur, oxygen, and carbon nucleophiles with organic halides can be
achieved under mild conditions (−40 to 30 °C) through
the use of light and a copper catalyst. Insight into the various mechanisms
by which these reactions proceed may enhance our understanding of
chemical reactivity and facilitate the development of new methods.
In this report, we apply an array of tools (EPR, NMR, transient absorption,
and UV–vis spectroscopy; ESI–MS; X-ray crystallography;
DFT calculations; reactivity, stereochemical, and product studies)
to investigate the photoinduced, copper-catalyzed coupling of carbazole
with alkyl bromides. Our observations are consistent with pathways
wherein both an excited state of the copper­(I) carbazolide complex
([CuI(carb)2]−) and an excited
state of the nucleophile (Li­(carb)) can serve as photoreductants of
the alkyl bromide. The catalytically dominant pathway proceeds from
the excited state of Li­(carb), generating a carbazyl radical and an
alkyl radical. The cross-coupling of these radicals is catalyzed by
copper via an out-of-cage mechanism in which [CuI(carb)2]− and [CuII(carb)3]− (carb = carbazolide), both of which have been
identified under coupling conditions, are key intermediates, and [CuII(carb)3]− serves as the persistent
radical that is responsible for predominant cross-coupling. This study
underscores the versatility of copper­(II) complexes in engaging with
radical intermediates that are generated by disparate pathways, en
route to targeted bond constructions.