Mild and Regioselective Synthesis of 3‐CF3‐Pyrazoles by the AgOTf‐Catalysed Reaction of CF3‐Ynones with Hydrazines

Gold‐ and silver‐catalysed reactions of trifluoromethylated ynones with aryl (alkyl) hydrazines were investigated. The use of (THD‐Dipp)AuOTf and AgOTf resulted in quick heterocyclization reactions to selectively give 3‐CF3‐pyrazoles. AgOTf was found to be the catalyst of choice, and various 3‐CF3‐p...

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Bibliographic Details
Published in:European journal of organic chemistry 2018-08, Vol.2018 (27-28), p.3750-3755
Main Authors: Topchiy, Maxim A., Zharkova, Daria A., Asachenko, Andrey F., Muzalevskiy, Vasiliy M., Chertkov, Vyacheslav A., Nenajdenko, Valentine G., Nechaev, Mikhail S.
Format: Article
Language:English
Subjects:
Aromatic compounds
Chemical synthesis
Fluorinated compounds
Fluorine
Functional groups
Gold
Hydrazines
Nitrogen heterocycles
Pyrazole
Pyrazoles
Regioselectivity
Silver
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Summary:Gold‐ and silver‐catalysed reactions of trifluoromethylated ynones with aryl (alkyl) hydrazines were investigated. The use of (THD‐Dipp)AuOTf and AgOTf resulted in quick heterocyclization reactions to selectively give 3‐CF3‐pyrazoles. AgOTf was found to be the catalyst of choice, and various 3‐CF3‐pyrazoles were formed in up to 99 % isolated yield with high regioselectivity. The reaction has a broad scope: 3‐CF3‐pyrazoles with alkyl and aryl substituents as well as different functional groups can be prepared by this approach. The known pyrazole drugs Celebrex® and SC‐560 were efficiently prepared to demonstrate the utility of the method. Mechanistic investigations revealed that the reaction involves the formation of a hemiaminal as a key intermediate. An efficient synthesis of 3‐CF3‐pyrazoles through the silver‐catalysed reaction of trifluoromethylated ynones with aryl (alkyl) hydrazines was developed. The heterocyclization took place very quickly and with high regioselectivity to give 3‐CF3‐pyrazoles in up to 99 % isolated yield. The known pyrazole drugs Celebrex® and SC‐560 were efficiently prepared to demonstrate the utility of the method.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.201800208