Palladium-Catalyzed Chelation-Assisted Regioselective Oxidative Dehydrogenative Homocoupling/Ortho-Hydroxylation in N-Phenylpyrazoles

Abstract

A palladium-catalyzed pyrazole-directed regioselective oxidative C(sp2)-H functionalization of the N-phenyl ring in N-phenylpyrazoles to afford either a biaryl bis-pyrazole (via dehydrogenative homocoupling) or N-(o-hydroxyphenyl)pyrazole (via C-H oxygenation) or their mixture is described. The substitutions on the N-phenyl ring and the pyrazole ring and the dilution of the reaction medium with respect to the TFA/TFAA mixture (substrate concentration) have a remarkable influence on the outcome of the reaction. It was discovered that if the reactions were performed under highly dilute conditions (ca. 10 times) then N-(o-hydroxyphenyl)pyrazoles were the major or the sole products.

Pd‐Catalyzed Late‐Stage Monoacetoxylation and Monoiodination of 4‐Alkyl‐1,5‐diaryl‐1 H‐pyrazole‐3‐carboxylates via Direct Csp2−H Bond Activation

“…However, when methoxyacetic acid or bromoacetic acid wereu sed, the hydrolysisp roduct 3eb was obtained insteado ft he direct acyloxylatedp roducts. [18] When iodoacetic acid was used as the solvent under otherwise identicalc onditions, however, we did not obtain the expected acyloxylated product or hydrolysis product. Surprisingly,t he iodination of 1e was found to deliver the product 4e in an excellent yield of 90 %( Scheme 4).…”

Synthesis of Phenolic Compounds via Palladium Catalyzed C−H Functionalization of Arenes

“…described palladium‐catalyzed regioselective C(sp 2 )−H hydroxylation of N ‐phenyl ring of N ‐phenylpyrazole under oxidative condition. Along with the desired hydroxylated product, the formation of biaryl bis‐pyrazole via dehydrogenative homo‐coupling was also realized in this reaction (Figure ) . The yield of the desired product depends upon two important factors including a) the substitution on both the N ‐phenyl and pyrazole rings and b) the dilution of the reaction medium with respect to trifluoroacetic acid (TFA)/trifluoroacetic anhydride (TFAA) mixture.…”

Cycloamination strategies for renewable N-heterocycles

“…Pyrazoles are a class of structural motifs prevalent in biologically active agents and medicines, notably, Lexiscan, Xalkori, Celebrex, and Viagra, 151 and these motifs are also present in dyes and they are utilized as ligands for metal catalysts. 152,153 The synthesis of pyrazole derivative 32 from acetic anhydride reacting with glucose phenylosazone 31 which is readily derivable from glucose and phenylhydrazine in the presence of acetic acid was first reported by El Khadem et al (Scheme 11).…”