Fluorinated Pyrazoles and Indazoles

Development and Mechanistic Investigations of a Base-Free Suzuki–Miyaura Cross-Coupling of α,α-Difluoroacetamides via C–N Bond Cleavage

“…For instance, α-fluorinated α′,β′-unsaturated ketones have recently attracted much interest as advanced intermediates for the synthesis of fluoroalkyl-substituted heterocycles and most notably pyrazole-based drugs and agrochemicals. However, methods to access these compounds remain sporadic and often rely on multiple-step pathways combined with the use of specialized reagents . Pleasingly, the successful participation of trans -β-styrylboronic acid in the cross-coupling reaction with 1g through C (acyl) –N bond activation provides a straightforward access to α,α-difluorinated enone 3 in a good yield.…”

Fluoroalkyl Amino Reagents (FARs): A General Approach towards the Synthesis of Heterocyclic Compounds Bearing Emergent Fluorinated Substituents

“…Whereas synthetics approaches towards pyrazoles bearing “classical” fluorinated substituents (F and CF 3 ) have been widely studied and reviewed by Fustero et al [ 78 ], the introduction of fluoroalkyl groups other than CF 3 onto various N-based heterocycles is still the focus of intense research interest. In 2008, Pazenok et al reported the utilization of TFEDMA for the preparation of ethyl 3-(difluoromethyl)-1-methyl-1 H -pyrazole-4-carboxylate (DFMMP), the key intermediate of Bixafen ® (a modern SDHI fungicide) [ 79 ].…”

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

“…Fluorinated pyrimidines, pyrimidine analogues and pyrazoles [20,21] play a prominent role in several clinically important pharmaceuticals [22][23][24][25]. These compounds act against HIV or HIV-related diseases [26], such as opportunistic fungal infections, and represent nucleoside analogues which can either act as antimetabolites or as nucleoside reverse transcriptase inhibitors (NRTIs).…”