Medicinally Relevant Modification of the Isoquinoline-1,3-dione Scaffold via Metal-Free Arylation and Fluorination of Diazo Homophthalimides­ in Brønsted Acids

Andrei Golushko; Dmitry Dar’in; Grigory Kantin; Natalia Guranova; Aleksander V. Vasilyev; Mikhail Krasavin

doi:10.1055/s-0037-1611882

Synthesis, Table of Contents

Synthesis 2019; 51(20): 3815-3824
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

Andrei Golushko

^aSaint Petersburg State University, Saint Petersburg 199034, Russian Federation Email: m.krasavin@spbu.ru

,

Dmitry Dar’in

^aSaint Petersburg State University, Saint Petersburg 199034, Russian Federation Email: m.krasavin@spbu.ru

,

Grigory Kantin

^aSaint Petersburg State University, Saint Petersburg 199034, Russian Federation Email: m.krasavin@spbu.ru

,

Natalia Guranova

^aSaint Petersburg State University, Saint Petersburg 199034, Russian Federation Email: m.krasavin@spbu.ru

,

Aleksander V. Vasilyev∗

^aSaint Petersburg State University, Saint Petersburg 199034, Russian Federation Email: m.krasavin@spbu.ru

^bDepartment of Chemistry, Saint Petersburg State Forest Technical University, Institutsky per. 5, Saint Petersburg 194021, Russian Federation

,

Mikhail Krasavin∗

^aSaint Petersburg State University, Saint Petersburg 199034, Russian Federation Email: m.krasavin@spbu.ru

› Author Affiliations

Abstract

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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)-dione

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References

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Supplementary Material

Supporting Information

Medicinally Relevant Modification of the Isoquinoline-1,3-dione Scaffold via Metal-Free Arylation and Fluorination of Diazo Homophthalimides­ in Brønsted Acids

Medicinally Relevant Modification of the Isoquinoline-1,3-dione Scaffold via Metal-Free Arylation and Fluorination of Diazo Homophthalimides in Brønsted Acids