Regio-Selective C3- and N-Alkylation of Indolines in Water under Air Using Alcohols
Milan Maji, Ishani Borthakur, Sameer Srivastava and Sabuj Kundu*
*Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, Uttar Pradesh,
India, Email: sabuj
iitk.ac.in
M. Maji, I. Borthakur, S. Srivastava, S. Kundu, J. Org. Chem., 2022, 87, 5603-5616.
DOI: 10.1021/acs.joc.1c03040
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Abstract
Iridium-catalyzed tandem dehydrogenation of N-heterocycles and alcohols enables regio-selective C-H and N-H bond functionalizations of indolines to provide a diverse range of N- and C3-alkylated indolines/indoles. The practical applicability of this methodology was demonstrated by the preparative-scale synthesis and synthesis of a psychoactive drug, N,N-dimethyltryptamine.
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proposed mechanism
Details
The article discusses a novel method for regio-selective C3- and N-alkylation of indolines using alcohols in water under air, facilitated by a cooperative iridium catalyst. This approach leverages the tandem dehydrogenation of N-heterocycles and alcohols, providing an eco-friendly alternative to traditional methods that often require organic solvents. The study highlights the synthesis of various N- and C3-alkylated indolines/indoles, demonstrating the practical applicability through preparative-scale synthesis and the production of the psychoactive drug N,N-dimethyltryptamine (DMT). The research includes extensive kinetic and control experiments, as well as density functional theory (DFT) calculations, to propose a catalytic cycle and understand the reaction mechanism. The findings emphasize the advantages of using water as a solvent, such as its abundance, low cost, and environmental friendliness, making the methodology suitable for both academic and industrial applications. The study also explores the scope of the protocol with a wide range of primary alcohols, achieving good to excellent yields. This work represents a significant advancement in the development of greener and sustainable synthetic protocols for the functionalization of indolines.
Key Words
ID: J42-Y2022
