Synthesis 2019; 51(20): 3815-3824
DOI: 10.1055/s-0037-1611882
paper
© Georg Thieme Verlag Stuttgart · New York

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

Andrei Golushko
a  Saint Petersburg State University, Saint Petersburg 199034, Russian Federation   Email: m.krasavin@spbu.ru
,
Dmitry Dar’in
a  Saint Petersburg State University, Saint Petersburg 199034, Russian Federation   Email: m.krasavin@spbu.ru
,
Grigory Kantin
a  Saint Petersburg State University, Saint Petersburg 199034, Russian Federation   Email: m.krasavin@spbu.ru
,
Natalia Guranova
a  Saint Petersburg State University, Saint Petersburg 199034, Russian Federation   Email: m.krasavin@spbu.ru
,
Aleksander V. Vasilyev
a  Saint Petersburg State University, Saint Petersburg 199034, Russian Federation   Email: m.krasavin@spbu.ru
b  Department of Chemistry, Saint Petersburg State Forest Technical University, Institutsky per. 5, Saint Petersburg 194021, Russian Federation
,
Mikhail Krasavin
a  Saint Petersburg State University, Saint Petersburg 199034, Russian Federation   Email: m.krasavin@spbu.ru
› Author Affiliations
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.

Supporting Information

 
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