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Ligand‐controlled Regiodivergent C−H Alkenylation of Pyrazoles and its Application to the Synthesis of Indazoles
Author(s) -
Kim Hyun Tae,
Ha Hyeri,
Kang Geunhee,
Kim Og Soon,
Ryu Ho,
Biswas Abul Kalam,
Lim Sang Min,
Baik MuHyun,
Joo Jung Min
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201709162
Subject(s) - chemistry , regioselectivity , indazole , ligand (biochemistry) , pyrazole , electrophile , trifluoroacetic acid , palladium , catalysis , pivalic acid , combinatorial chemistry , hydrazine (antidepressant) , organic chemistry , medicinal chemistry , biochemistry , receptor , chromatography
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.