Site-selective arene C-H amination via photoredox catalysis
Lighting the way to aryl C-N bonding
Medicinal chemists like to add N bonds to the C atoms of aromatic rings to make bioactive compounds. By harnessing the energy in visible light, Romero et al. made these links and transformed C-H into C-N bonds. They used a blue-absorbing acridinium ion to activate a ring C for an incoming N partner. A nitroxyl radical co-catalyst (TEMPO) then choreographed the transfer of the H atom to O. The reaction worked for a broad range of substrates, including ammonium as a N source.
Science, this issue p. 1326
Abstract
Over the past several decades, organometallic cross-coupling chemistry has developed into one of the most reliable approaches to assemble complex aromatic compounds from preoxidized starting materials. More recently, transition metal–catalyzed carbon-hydrogen activation has circumvented the need for preoxidized starting materials, but this approach is limited by a lack of practical amination protocols. Here, we present a blueprint for aromatic carbon-hydrogen functionalization via photoredox catalysis and describe the utility of this strategy for arene amination. An organic photoredox-based catalyst system, consisting of an acridinium photooxidant and a nitroxyl radical, promotes site-selective amination of a variety of simple and complex aromatics with heteroaromatic azoles of interest in pharmaceutical research. We also describe the atom-economical use of ammonia to form anilines, without the need for prefunctionalization of the aromatic component.
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Supplementary Material
Summary
Materials and Methods
Tables S1 to S4
NMR Spectra
Resources
File (aac9895-romero-sm.pdf)
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Published In
Science
Volume 349 | Issue 6254
18 September 2015
18 September 2015
Copyright
Copyright © 2015, American Association for the Advancement of Science.
Submission history
Received: 9 July 2015
Accepted: 19 August 2015
Published in print: 18 September 2015
Acknowledgments
Financial support was provided by the David and Lucile Packard Foundation, Merck, and an Amgen Young Investigator Award. N.A.R is grateful for an NSF Graduate Fellowship, and K.A.M. was supported by a Francis Preston Venable Graduate Fellowship. A provisional patent has been filed on the methods presented here (U.S. patent application no. 62/170,632).
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