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

Research output

Abstract

Protonation of 4-diazoisoquinoline-1,3(2 H,4 H)-diones in Bronsted acids gives rise to diazonium cations that can be trapped with arenes to give 4-arylisoquinoline-1,3(2 H,4 H)-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.

Original languageEnglish
Pages (from-to)3815-3824
Number of pages10
JournalSynthesis (Germany)
Volume51
Issue number20
DOIs
Publication statusPublished - 1 Jan 2019

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Fluorination
Scaffolds
Cations
Positive ions
Metals
Acids
Fluorine
Protonation
Carboxylic Acids
Carboxylic acids
Atoms
isoquinoline

Scopus subject areas

  • Catalysis
  • Organic Chemistry

Cite this

@article{6c57009d855f4c23993b2621641c5f75,
title = "Medicinally Relevant Modification of the Isoquinoline-1,3-dione Scaffold via Metal-Free Arylation and Fluorination of Diazo Homophthalimides{\^A}-in Bronsted Acids",
abstract = "Protonation of 4-diazoisoquinoline-1,3(2 H,4 H)-diones in Bronsted acids gives rise to diazonium cations that can be trapped with arenes to give 4-arylisoquinoline-1,3(2 H,4 H)-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.",
keywords = "arylation, Bronsted acids, diazo compounds, fluorohalogenation, Friedel-Crafts reaction, homophthalimides, isoquinoline-1,3(2 H,4 H)-dione, monofluorination",
author = "Andrei Golushko and Dmitry Dar'in and Grigory Kantin and Natalia Guranova and Vasilyev, {Aleksander V.} and Mikhail Krasavin",
year = "2019",
month = "1",
day = "1",
doi = "10.1055/s-0037-1611882",
language = "English",
volume = "51",
pages = "3815--3824",
journal = "Synthesis",
issn = "0039-7881",
publisher = "Georg Thieme Verlag",
number = "20",

}

TY - JOUR

T1 - Medicinally Relevant Modification of the Isoquinoline-1,3-dione Scaffold via Metal-Free Arylation and Fluorination of Diazo HomophthalimidesÂ-in Bronsted Acids

AU - Golushko, Andrei

AU - Dar'in, Dmitry

AU - Kantin, Grigory

AU - Guranova, Natalia

AU - Vasilyev, Aleksander V.

AU - Krasavin, Mikhail

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Protonation of 4-diazoisoquinoline-1,3(2 H,4 H)-diones in Bronsted acids gives rise to diazonium cations that can be trapped with arenes to give 4-arylisoquinoline-1,3(2 H,4 H)-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.

AB - Protonation of 4-diazoisoquinoline-1,3(2 H,4 H)-diones in Bronsted acids gives rise to diazonium cations that can be trapped with arenes to give 4-arylisoquinoline-1,3(2 H,4 H)-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.

KW - arylation

KW - Bronsted acids

KW - diazo compounds

KW - fluorohalogenation

KW - Friedel-Crafts reaction

KW - homophthalimides

KW - isoquinoline-1,3(2 H,4 H)-dione

KW - monofluorination

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U2 - 10.1055/s-0037-1611882

DO - 10.1055/s-0037-1611882

M3 - Article

AN - SCOPUS:85072991940

VL - 51

SP - 3815

EP - 3824

JO - Synthesis

JF - Synthesis

SN - 0039-7881

IS - 20

ER -