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. 2011 Dec 14;133(49):19960-5.
doi: 10.1021/ja2087085. Epub 2011 Nov 16.

Metal-free intermolecular oxidative C-N bond formation via tandem C-H and N-H bond functionalization

Abhishek A Kantak  1 , Shathaverdhan Potavathri, Rose A Barham, Kaitlyn M Romano, Brenton DeBoef
Affiliations

Metal-free intermolecular oxidative C-N bond formation via tandem C-H and N-H bond functionalization

Abhishek A Kantak et al. J Am Chem Soc. .

Abstract

The development of a novel intermolecular oxidative amination reaction, a synthetic transformation that involves the simultaneous functionalization of both a N-H and C-H bond, is described. The process, which is mediated by an I(III) oxidant and contains no metal catalysts, provides a rapid and green method for synthesizing protected anilines from simple arenes and phthalimide. Mechanistic investigations indicate that the reaction proceeds via nucleophilic attack of the phthalimide on an aromatic radical cation, as opposed to the electrophilic aromatic amination that has been reported for other I(III) amination reactions. The application of this new reaction to the synthesis of a variety of substituted aniline derivatives is demonstrated.

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Figures

Figure 1
Figure 1
Examples of high-value molecules containing anilines
Figure 2
Figure 2
Kinetic analysis of oxidative amination reaction with various amounts of PhI(OAc)2 (oxidant) and phthalimide.
Scheme 1
Scheme 1
Oxidative amination of substituted arenes
Scheme 2
Scheme 2
Two possible mechanisms for the oxidative amination
Scheme 3
Scheme 3
Resonance structures of the aryl radical cation explain the observed regioselectivities.
Scheme 4
Scheme 4
Formation of substitution products corroborates the intermediacy of arene radical cations.
See this image and copyright information in PMC

References

    1. For recent reviews describing oxidative C-C formation, see: Cho SH, Kim JY, Kwak J, Chang S. Chem. Soc. Rev. 2011;40:5068–5083.Yeung CS, Dong VM. Chem. Rev. 2011;111:1215.McGlacken GP, Bateman LM. Chem. Soc. Rev. 2009;38:2447.

    1. For recent reviews describing C-N formation via nitreneoid intermediates, see: Davies HML, Manning JR. Nature. 2008;451:417.Müller P, Fruit C. Chem. Rev. 2003;103:2905.

    1. For a partial review, see: ref. , pp. 12-16.

    1. For recent examples of Cu and Pd-catalyzed aminations, see: Tsang WCP, Zheng N, Buchwald SL. J. Am. Chem. Soc. 2005;127:14560.Thu H-Y, Yu W-Y, Che CM. J. Am. Chem. Soc. 2006;128:9048.Tsang WCP, Munday RH, Brasche G, Zheng N, Buchwald SL. J. Org. Chem. 2008;73:7603.Li B, Tian S, Fang Z, Shi Z. Angew. Chem. Int. Ed. 2008;47:1115.Jordan-Hore JA, Johansson CCC, Beck EM, Gaunt MJ. J. Am. Chem. Soc. 2008;130:16184.Miura T, Murakami M. Chem. Lett. 2009;38:328.John A, Nicholas KM. J. Org. Chem. 2011;76:4158.Xiao B, Gong T-J, Xu J, Liu Z-J, Liu L. J. Am. Chem. Soc. 2011;133:1466.Sun K, Li Y, Xiong T, Zhang J, Zhan Q. J. Am. Chem. Soc. 2011;133:1694.Yoo EJ, Ma S, Mei T-S, Chan KSL, Yu J-Q. J. Am. Chem. Soc. 2011;133:7652.

    1. For a recent examples of a metal-free amination, see: Cho SH, Yoon J, Chang S. J. Am. Chem. Soc. 2011;133:5696.Lamani M, Prabhu KR. Iodine-Catalyzed Amination of Benzoxazoles: A Metal-Free Route to 2-Aminobenzoxazoles under Mild Conditions. J. Org. Chem. 2011 [Online early access]. DOI: 10.1021/jo201402a. PublishedOnline: Aug 25, 2011.

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