Ligand‐controlled Regiodivergent C−H Alkenylation of Pyrazoles and its Application to the Synthesis of Indazoles

Regioselective C4‐, C5‐, and di‐alkenylations of pyrazoles were achieved. An electrophilic Pd catalyst generated by trifluoroacetic acid (TFA) and 4,5‐diazafluoren‐9‐one (DAF) leads to C4‐alkenylation, whereas KOAc and mono‐protected amino acid (MPAA) ligand Ac‐Val‐OH give C5‐alkenylation. A combina...

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Published in:Angewandte Chemie International Edition 2017-12, Vol.56 (51), p.16262-16266
Main Authors: Kim, Hyun Tae, Ha, Hyeri, Kang, Geunhee, Kim, Og Soon, Ryu, Ho, Biswas, Abul Kalam, Lim, Sang Min, Baik, Mu‐Hyun, Joo, Jung Min
Format: Article
Language:English
Subjects:
Acetic acid
alkenylation
Amino acids
Chemical reactions
C−H activation
indazole
Ligands
Organic chemistry
Oxidation
Palladium
Pyrazole
Pyrazoles
Silver
Trifluoroacetic acid
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Summary:Regioselective C4‐, C5‐, and di‐alkenylations of pyrazoles were achieved. An electrophilic Pd catalyst generated by trifluoroacetic acid (TFA) and 4,5‐diazafluoren‐9‐one (DAF) leads to C4‐alkenylation, whereas KOAc and mono‐protected amino acid (MPAA) ligand Ac‐Val‐OH give C5‐alkenylation. A combination of palladium acetate, silver carbonate, and pivalic acid affords dialkenylation products. Annulation through sequential alkenylation, thermal 6π‐electrocyclization, and oxidation gives functionalized indazoles. This comprehensive strategy greatly expands the range of readily accessible pyrazole and indazole derivatives, enabling useful regiodivergent C−H functionalization of pyrazoles and other heteroaromatic systems. A regioselective C−H functionalization of pyrazoles was developed to provide C4‐, C5‐, and di‐alkenyl pyrazoles using three distinctive Pd catalytic systems. The systematic preparation of alkenyl pyrazoles enabled the synthesis of multifunctionalized indazoles and π‐extended pyrazoles from readily available, inexpensive pyrazoles and olefins.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201709162