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Synthesis 2019; 51(20): 3815-3824
DOI: 10.1055/s-0037-1611882
DOI: 10.1055/s-0037-1611882
paper
Medicinally Relevant Modification of the Isoquinoline-1,3-dione Scaffold via Metal-Free Arylation and Fluorination of Diazo Homophthalimides in Brønsted Acids
Synthesis of diazo homophthalimides was supported by the Russian Science Foundation Grant No. 19-75-30008. Electrophilic reactions of diazo compounds with arenes and fluorination reactions were supported by the Russian Science Foundation Grant No. 18-13-00008.Further Information
Publication History
Received: 16 May 2019
Accepted after revision: 13 June 2019
Publication Date:
08 July 2019 (online)
Abstract
Protonation of 4-diazoisoquinoline-1,3(2H,4H)-diones in Brønsted acids gives rise to diazonium cations that can be trapped with arenes to give 4-arylisoquinoline-1,3(2H,4H)-diones (homophthalimides). This provides a new, metal-free approach to 4-aryltetrahydroisoquinolines (obtainable from respective homophthalimides by reduction). Similarly, a fluorine atom can be introduced by trapping the diazonium cation with HF. This led to the preparation of the first examples of 4-monofluoro-substituted isoquinoline-1,3-diones (as well as their 4-bromo-4-fluoro and 4-chloro-4-fluoro variants), important carboxylic acid isosteres on their own and precursors of useful 4-fluorotetrahydroisoquinoline building blocks.
Key words
homophthalimides - diazo compounds - arylation - Friedel–Crafts reaction - monofluorination - fluorohalogenation - Brønsted acids - isoquinoline-1,3(2H,4H)-dioneSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611882. Copies of 1H and 13C NMR spectra and crystallographic data are provided.
- Supporting Information
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