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Isoquinolone-4-Carboxylic Acids by Ammonia-Ugi-4CR and Copper-Catalyzed Domino Reaction.

ABSTRACT: Highly substituted isoquinolone-4-carboxylic acid is an important bioactive scaffold; however, it is challenging to access it in a general and short way. A Cu-catalyzed cascade reaction was successfully designed involving the Ugi postcyclization strategy by using ammonia and 2-halobenzoic acids as crucial building blocks. Privileged polysubstituted isoquinolin-1(2H)-ones were constructed in a combinatorial format with generally moderate to good yields. The protocol, with a ligand-free catalytic system, shows a broad substrate scope and good functional group tolerance toward excellent molecular diversity. Free 4-carboxy-isoquinolone is now for the first time generally accessible by a convergent multicomponent reaction protocol.

SUBMITTER: Wang Q

PROVIDER: S-EPMC8291606 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Isoquinolone-4-Carboxylic Acids by Ammonia-Ugi-4CR and Copper-Catalyzed Domino Reaction.

Wang Qian Q Mgimpatsang Kumchok C KC Li Xin X Dömling Alexander A

The Journal of organic chemistry 20210629 14

Highly substituted isoquinolone-4-carboxylic acid is an important bioactive scaffold; however, it is challenging to access it in a general and short way. A Cu-catalyzed cascade reaction was successfully designed involving the Ugi postcyclization strategy by using ammonia and 2-halobenzoic acids as crucial building blocks. Privileged polysubstituted isoquinolin-1(2<i>H</i>)-ones were constructed in a combinatorial format with generally moderate to good yields. The protocol, with a ligand-free cat ...[more]

PMID: 34184894

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