Issue 7, 2024

Synthesis of 6-azaindoles via formal electrophilic [4 + 1]-cyclization of 3-amino-4-methyl pyridines: new frontiers of diversity

Abstract

A scalable and efficient synthesis of 2-trifluoromethyl-3-trifluoroacetyl-6-azaindoles from 3-amino-4-methylpyridines under treatment with TFAA is disclosed. The reaction scope and limitations of pyridine and electrophilic components were investigated. Activation of the methyl group in aminomethylpyridines under mildly acidic conditions appeared promising for significantly expanding the scope of principally novel substrates. Examining the pyridine components using trifluoroacetic anhydride (TFAA) as a model electrophile allowed us to divide them into three groups with different impacts on the reaction outcome. Among the electrophilic components, difluoroacetic anhydride (DFAA), trichloroacetic anhydride (TCAA) and Vilsmeier–Haack reagent (VHR) were inspected. Combining the results led to a cyclization mechanism rationalizing our observations.

Graphical abstract: Synthesis of 6-azaindoles via formal electrophilic [4 + 1]-cyclization of 3-amino-4-methyl pyridines: new frontiers of diversity

Supplementary files

Article information

Article type
Research Article
Submitted
21 Nov 2023
Accepted
08 Feb 2024
First published
08 Feb 2024

Org. Chem. Front., 2024,11, 2088-2094

Synthesis of 6-azaindoles via formal electrophilic [4 + 1]-cyclization of 3-amino-4-methyl pyridines: new frontiers of diversity

S. P. Ivonin, V. V. Voloshchuk, E. B. Rusanov, S. Suikov, S. V. Ryabukhin and D. M. Volochnyuk, Org. Chem. Front., 2024, 11, 2088 DOI: 10.1039/D3QO01937C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements