Copper‐Catalyzed Trifluoromethylation of N,N‐Dialkylhydrazones

Abstract

Mild and practical: Trifluoromethylation of (hetero)aromatic aldehyde N,N‐dialkylhydrazones was achieved at room temperature by using Togni's trifluoromethylation reagent under CuCl catalysis (see scheme). This simple reaction is believed to occur by a CF3‐radical‐transfer mechanism and yields useful trifluoromethylated building blocks.

An overview of reductive trifluoromethylation reactions using electrophilic ‘+CF3’ reagents

“…Analogously, a complete regioselective three-component azidoand aminotrifluoromethylation of alkenes (52) under mild conditions was developed by using visible-light-driven photoredox catalyst [Ru(bpy) 3 ][PF 6 ] 2 and electrophilic ' þ CF 3 ' reagent (1c). 25 Various substituted styrenes as well as activated and non-activated alkenes are readily difunctionalized, affording b-trifluoromethylated azides (53) and amines (54) in good yields. Reaction mechanisms similar to that of the previously reported oxytrifluoromethylation of alkenes are suggested, in which CF 3 is generated from the reduction of 1c by activated [Ru(bpy) 3 ]*[PF 6 ] 2 via a SET process.…”

“…53 First, Togni's reagent 65a is reduced by Cu(I) to afford a CF 3 eI-ArCO 2 [Cu(II)] radical or a CF 3 radical, which reacts with 178 Furthermore, Bouyssi and Baudoin developed a practical procedure for the reductive trifluoromethylation of (hetero)aromatic aldehyde N,N-dialkylhydrazones with 65a and CuCl catalyst (Scheme 47). 54 To gain an insight into the possible mechanism of the reaction, the radical-trapping experiment was performed with TEMPO, in which the formation of the desired trifluoromethylated product was almost completely inhibited, and instead the TEMPO-CF 3 adduct was formed in almost quantitative yield, suggesting a radical process (Scheme 47). The reaction pathway may begin with the reduction of 65a by CuI via a single electron transfer (SET) to generate 96, which acts as a CF 3 radical donor.…”

Denitrogenative Hydrotrifluoromethylation of Benzaldehyde Hydrazones: Synthesis of (2,2,2‐Trifluoroethyl)arenes

“…[20] We were interested in exploitingt he electrophilic nature of 2 [21] to develop at ransitionmetal-free synthesis of 1,b ye xposingi tt oas uitable benzylic nucleophile such as ah ydrazone. [22] Arylaldehyde-derivedh ydrazones readily undergo trifluoromethylation at the azomethine carbon, [23] but to the best of our knowledge,t his reactivity has not been coupled with a denitrogenation event. Given our interest in HVI-mediated gem-difunctionalization reactions of diazo compounds and hydrazones, [24] we aimed to interrupt aW olff-Kishner reduction by having an anionic intermediate engage 2 instead of a Scheme1.Various syntheses of (2,2,2-trifluoroethyl)arenes 1.[a] Dr.…”

Gold‐Catalyzed Highly Selective Photoredox C(sp2)−H Difluoroalkylation and Perfluoroalkylation of Hydrazones

“…[10,11] Both Barriault [10a,b] and co-workers and our group [10c] have shown that [Au 2 (m-dppm) 2 ] 2+ is an efficient photocatalyst to readily generate active carbon-centered radicals from organic halides.W eh ave now examined the possibility of ad irect CÀH difluoroalkylation of benzaldehyde (1a)a nd its synthetic equivalents (oxime 2a,imines 3a-5a,and hydrazones 6a-9a) with diethyl (bromodifluoromethyl)phosphonate and ethyl 2bromo-2,2-difluoroacetate by using [Au 2 (m-dppm) 2 ](OTf) 2 (10)a st he photocatalyst in sunlight [12] (Scheme 1). [14] Even though the coppercatalyzed trifluoromethylation of N,N-dialkyl hydrazones with Tognis reagent is known, [15] atransition-metal-catalyzed C À Hd ifluoro-and perfluoroalkylation of hydrazones by photocatalysis with inexpensive and readily available R F À Br reagents is unprecedented. [14] Even though the coppercatalyzed trifluoromethylation of N,N-dialkyl hydrazones with Tognis reagent is known, [15] atransition-metal-catalyzed C À Hd ifluoro-and perfluoroalkylation of hydrazones by photocatalysis with inexpensive and readily available R F À Br reagents is unprecedented.…”

“…[13] The results demonstrate that hydrazones 8a and 9a can undergo ad ifluoroalkylation reaction in moderate yields with excellent stereo-and regioselectivities. [14] Even though the coppercatalyzed trifluoromethylation of N,N-dialkyl hydrazones with Tognis reagent is known, [15] atransition-metal-catalyzed C À Hd ifluoro-and perfluoroalkylation of hydrazones by photocatalysis with inexpensive and readily available R F À Br reagents is unprecedented.…”