Synfacts 2010(9): 0995-0995  
DOI: 10.1055/s-0030-1258002
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart ˙ New York

Copper-Catalyzed Synthesis of Isatins from Formyl-N-arylformamides

Contributor(s): Victor Snieckus, Timothy Hurst
B.-X. Tang, R.-J. Song, C.-Y. Wu, Y. Liu, M.-B. Zhou, W.-T. Wei, G.-B. Deng, D.-L. Yin, J.-H. Li*
Hunan Normal University, Changsha, P. R. of China
Further Information

Publication History

Publication Date:
23 August 2010 (online)

Significance

The synthesis of isatins 2 via the copper-catalyzed intramolecular oxidative cyclization of formyl-N-arylformamides 1 is described. Although unprotected N-arylformamides (R² = H) do not participate in the reaction, a variety of N-alkylated substrates perform equally well. Electron-rich substrates were found to give the best yields (typically >75%), whilst those bearing strong EWGs (Ac, CF3) gave only moderate yields (50% and 30%, respectively). Notably, substrates with meta-substituents led to mixtures of products. However, ortho-substituted derivatives were well tolerated. A mechanism is proposed involving intermediates 3 and 4 based on extensive KIE and control experiments, in situ FTIR, and HRMS analysis.