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Rhodium(III)-catalyzed arene and alkene C-H bond functionalization leading to indoles and pyrroles.
J Am Chem Soc. 2010 Dec 29; 132(51):18326-39.JA

Abstract

Recently, the rhodium(III)-complex [Cp*RhCl(2)](2) 1 has provided exciting opportunities for the efficient synthesis of aromatic heterocycles based on a rhodium-catalyzed C-H bond functionalization event. In the present report, the use of complexes 1 and its dicationic analogue [Cp*Rh(MeCN)(3)][SbF(6)](2) 2 have been employed in the formation of indoles via the oxidative annulation of acetanilides with internal alkynes. The optimized reaction conditions allow for molecular oxygen to be used as the terminal oxidant in this process, and the reaction may be carried out under mild temperatures (60 °C). These conditions have resulted in an expanded compatibility of the reaction to include a range of new internal alkynes bearing synthetically useful functional groups in moderate to excellent yields. The applicability of the method is exemplified in an efficient synthesis of paullone 3, a tetracyclic indole derivative with established biological activity. A mechanistic investigation of the reaction, employing deuterium labeling experiments and kinetic analysis, has provided insight into issues of reactivity for both coupling partners as well as aided in the development of conditions for improved regioselectivity with respect to meta-substituted acetanilides. This reaction class has also been extended to include the synthesis of pyrroles. Catalyst 2 efficiently couples substituted enamides with internal alkynes at room temperature to form trisubstituted pyrroles in good to excellent yields. The high functional group compatibility of this reaction enables the elaboration of the pyrrole products into a variety of differentially substituted pyrroles.

Authors+Show Affiliations

Centre for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Canada K1N 6N5. dstuart@fas.harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21133376

Citation

Stuart, David R., et al. "Rhodium(III)-catalyzed Arene and Alkene C-H Bond Functionalization Leading to Indoles and Pyrroles." Journal of the American Chemical Society, vol. 132, no. 51, 2010, pp. 18326-39.
Stuart DR, Alsabeh P, Kuhn M, et al. Rhodium(III)-catalyzed arene and alkene C-H bond functionalization leading to indoles and pyrroles. J Am Chem Soc. 2010;132(51):18326-39.
Stuart, D. R., Alsabeh, P., Kuhn, M., & Fagnou, K. (2010). Rhodium(III)-catalyzed arene and alkene C-H bond functionalization leading to indoles and pyrroles. Journal of the American Chemical Society, 132(51), 18326-39. https://doi.org/10.1021/ja1082624
Stuart DR, et al. Rhodium(III)-catalyzed Arene and Alkene C-H Bond Functionalization Leading to Indoles and Pyrroles. J Am Chem Soc. 2010 Dec 29;132(51):18326-39. PubMed PMID: 21133376.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rhodium(III)-catalyzed arene and alkene C-H bond functionalization leading to indoles and pyrroles. AU - Stuart,David R, AU - Alsabeh,Pamela, AU - Kuhn,Michelle, AU - Fagnou,Keith, Y1 - 2010/12/06/ PY - 2010/12/8/entrez PY - 2010/12/8/pubmed PY - 2011/4/30/medline SP - 18326 EP - 39 JF - Journal of the American Chemical Society JO - J Am Chem Soc VL - 132 IS - 51 N2 - Recently, the rhodium(III)-complex [Cp*RhCl(2)](2) 1 has provided exciting opportunities for the efficient synthesis of aromatic heterocycles based on a rhodium-catalyzed C-H bond functionalization event. In the present report, the use of complexes 1 and its dicationic analogue [Cp*Rh(MeCN)(3)][SbF(6)](2) 2 have been employed in the formation of indoles via the oxidative annulation of acetanilides with internal alkynes. The optimized reaction conditions allow for molecular oxygen to be used as the terminal oxidant in this process, and the reaction may be carried out under mild temperatures (60 °C). These conditions have resulted in an expanded compatibility of the reaction to include a range of new internal alkynes bearing synthetically useful functional groups in moderate to excellent yields. The applicability of the method is exemplified in an efficient synthesis of paullone 3, a tetracyclic indole derivative with established biological activity. A mechanistic investigation of the reaction, employing deuterium labeling experiments and kinetic analysis, has provided insight into issues of reactivity for both coupling partners as well as aided in the development of conditions for improved regioselectivity with respect to meta-substituted acetanilides. This reaction class has also been extended to include the synthesis of pyrroles. Catalyst 2 efficiently couples substituted enamides with internal alkynes at room temperature to form trisubstituted pyrroles in good to excellent yields. The high functional group compatibility of this reaction enables the elaboration of the pyrrole products into a variety of differentially substituted pyrroles. SN - 1520-5126 UR - https://www.unboundmedicine.com/medline/citation/21133376/Rhodium_III__catalyzed_arene_and_alkene_C_H_bond_functionalization_leading_to_indoles_and_pyrroles_ L2 - https://doi.org/10.1021/ja1082624 DB - PRIME DP - Unbound Medicine ER -