A General Approach towards NH‐Pyr­azoles That Bear Diverse Fluoroalkyl Groups by Means of Fluorinated Iminium Salts

Abstract

A new and general approach to important fluoroalkyl-substituted pyrazoles has been developed. The approach is based on the use of fluoroalkyl amino reagents and their Lewis acid activation to form a fluoroalkyl iminium salt that acts as a formal "fluoroacyl transfer reagent". Their interaction with readily available fluoroalkyl azines followed by spontaneous cyclization of the formed intermediates under acidic condi-

Recent advances in the synthesis of fluorinated hydrazones

“…Tuneable regioselectivity and broad substitution patterns was achieved by these methods. 51,52 Between 2013 and 2016, Bouyssi and co-workers reported a mild procedure for triuoromethylation of (hetero)aromatic aldehyde or aldehyde N,N-dialkylhydrazones using the Togni hypervalent iodine reagent with copper catalysis (Scheme 19). [53][54][55][56] The reaction pathway was proposed to begin with the activation of Togni s reagent 61 by Cu I via single-electron transfer (SET) to form Cu II species 62, which could act as a tri-uoromethyl radical donor.…”

A Major Advance in the Synthesis of Fluoroalkyl Pyrazoles: Tuneable Regioselectivity and Broad Substitution Patterns

“…This providedh ighly functionalized pyrazoles with structural diversity,b ut had drawbacks such as low atom efficiency,d ifficultr emovalo fb enzophenone and limitation to N-H pyrazoles. [11] Herein, we report af acile, robust and scalables trategy to synthesize highly functionalized bis(fluoroalkyl)pyrazoles showing diverse substitution patterns at the 1-positionu nder mild conditions without the use of difficult-to-remove benzophenone, which allows tunable introductiono ff luorinated groups Rf 1 /Rf 2 in the 3-and 5-positions.…”

“…We developed a general approach towards bis(fluoroalkyl)pyrazoles based on the use of FARs and fluorinated azines derived from benzophenone to introduce CHF 2 , CHFCl and CHFCF 3 substituents. This provided highly functionalized pyrazoles with structural diversity, but had drawbacks such as low atom efficiency, difficult removal of benzophenone and limitation to N ‐H pyrazoles …”

Synthesis of Fluoroalkyl Pyrazoles from In‐Situ‐Generated C2F5CHN2 and Electron‐Deficient Alkenes

“…The only examples described in the literature are summarized in Scheme . In particular, CF 3 CHF‐substituted pyrazoles were obtained by Fustero and co‐workers by treating the corresponding alcohol with DAST, while Leroux, Pazenok, and colleagues started from CF 3 CHF‐substituted vinamidinium salts . Otherwise, the synthesis of CF 3 CHF‐substituted pyrazoles remains unexplored.…”