Exploring the Role of Coinage Metalates in Trifluoromethylation: A Combined Experimental and Theoretical Study

Abstract

Despite the knownn ucleophilic nature of [M(CF 3 ) 2 ] À (M = Cu, Ag, Au) complexes, their participation in trifluoromethylation reactions of aryl halides remains unexplored.H ere, for the first time, selective accesst oa [Cu(CF 3 ) 2 ] À species is reported, whichi su biquitous in Cumediated trifluoromethylations, and we rationalize its complex mechanistic scenario as well as its behavior compared to its silver and gold congeners through ac ombination of experimental and computational approaches.Undoubtedly, over the past years, trifluoromethyl organometallic compounds of coinage metalsh ave played ak ey role as reactive intermediates in organic synthesis. [1][2][3] In this context, fundamental studies on the reactivity of ate-type complexes as nucleophiles has received little attentionb ecause, until recently,o nly well-defined( Cat)[Au(CF 3 ) 2 ]c omplexes were isolable. [4] In 2018, we reported, for the first time, not only the isolation of au nique silver salt, (Cs)[Ag(CF 3 ) 2 ], but also its high efficiency as at ransmetalating reagent in Pd-catalyzed trifluoromethylations. [2d] Although differentl iterature reports have proposed the existence and involvemento fn ucleophilic[ Cu(CF 3 ) 2 ] À species in CÀCF 3 bond-forming reactions, their detailedc hemical behavior remains obscure. [3, 5] This can be attributed to challenges associatedw ith their selectivea ccess, their inherent instabilityand the existence of different neutraland ionic species in solution that are in equilibrium ( Figure 1).As part of our ongoing interest in the reactivity of ate-type complexes,w ew ondered whether it could be possible to unravel the potential of (Cat)[M(CF 3 ) 2 ]( M= Cu, Ag, Au) as reactive species in trifluoromethylation reactions and to compare/understandt heir performance. Herein, we explorep reviously inaccessible features of these rather unique [M(CF 3 ) 2 ] À species, including:i )adirect synthetic route fora ccessing unprecedented (Cs)[M(CF 3 ) 2 ]( M = Cu, Au) salts and their unambiguously characterization by single-crystal X-ray diffraction;i i) ac omprehensive experimental and computationala nalysis of coinage [M(CF 3 ) 2 ] À andt heir relative reactivity to ab enchmark aryl halide;a nd iii)the first experimentale vidence of the participation of [Cu(CF 3 ) 2 ] À in trifluoromethylation processes.Inspired by our previous results, we started our investigations by targeting access to (Cs)[M(CF 3 ) 2 ]( 1 M ,M= Cu, Au) using 1 Ag as aCF 3 shuttle. [2d] Gratifyingly,wewereable to in situ generate 1 Cu in quantitative yield using 1equiv of CuI and 1equiv of 1 Ag in THF or DMF at room temperature after one hour( reaction 1). [6] Although 1 Cu is insufficiently stable for isolation, [7] we confirmed its structure by using 19 FNMR spectroscopy,E SI-MS and single-crystal X-ray diffraction. [8] Thisr esult is certainly remarkable in view of the previously described difficulties to access to [Cu(CF 3 ) 2 ] À species in as electivem anner in solution. Underi dentical conditions, the reactionb etween 1 Ag and [AuCl(SMe...

Mechanistic Insight into Copper-Mediated Trifluoromethylation of Aryl Halides: The Role of CuI

“…In this case, these species were assigned as CF 3 Cu•KBr (−28.8 and an organocopper(III) species K + [Cu(CF 3 ) 4 ] − (−35.7 ppm) (Scheme1B). 17 Likewise, Yagupolskii and co-workers also reported, in 2010, that similar signals in the 19 F NMR spectrum that corresponded to the [CF To elucidate the structure of the observed [CF 3 Cu] species, several groups have tried to characterize the proposed structure by independent synthesis. In 2008, Vicic and co-workers reported the synthesis and characterization of a well-defined cuprate complex, [(SIMes) 2 Cu] + [Cu(CF 3 ) 2 ] − , with a chemical shift (−31.5 ppm in THF) close to those observed previously (Scheme 1D).…”

“…In 1986, the group of Burton reported the first spectroscopic studies of trifluoromethylcopper(I) species in this process (Scheme 1A). 15 A characteristic peak with a chemical shift of −28.8 ppm (A) in the 19 F NMR spectrum was generated upon mixing a solution of trifluoromethylzinc/ cadmium in DMF/HMPA with copper(I) salt at −50 °C. In the absence of HMPA, the peak disappeared at room temperature, and two new peaks at −32.3 ppm (B) and −35.5 ppm (C) in DMF were formed (Scheme 1A).…”

“…13a However, [(SIMes) 2 Cu] + [Cu(CF 3 ) 2 ] − reacted with aryl iodides sluggishly, and it was converted to more active neutral Cu(I) species [(SIMes)Cu(CF 3 )] that reacted with aryl iodides efficiently (Scheme 1). 18 In 2019, the groups of Peŕez-Temprano and Shen independently reported the preparation, characterization, and reactivity studies of crystalline ionic cuprate complexes Cs + [Cu(CF 3 ) 2 ] − (−31.1 ppm in DMF) 19 and [Ph 4 P] + [Cu(CF 3 ) 2 ] − (−31.4 ppm in THF or CDCl 3 ). 20 It was found that both complexes reacted with aryl iodides slowly at 50 or 100 °C (Scheme 1D).…”

“…20 DFT calculation by Peŕez-Temprano and co-workers proposed that the active copper species in the reaction was [(DMF)-Cu(CF 3 )], which was generated by thermal decomposition of [Cu(CF 3 )(I)] − . 19 Despite these advances in attempting to elucidate the active species in the copper-mediated/-catalyzed trifluoromethylation of aryl halides, several questions remain. (1) Is the species at −28.4 ppm in DMF [Cu(CF 3 )(I)] − ?…”

Nucleophilic Trifluoromethylation Reactions Involving Copper(I) Species: From Organometallic Insights to Scope

“…to devote our efforts towards unveiling the real role of cuprate species in nucleophilic trifluoromethylation reactions. 5 Recently, we were able to access, for the first time in a selective manner, [Cu(CF 3 )] 2 , ubiquitous in all the aforementioned transformations. We carried out the quantitative generation of these species in situ through a transmetalation reaction using its analogous silver ate-type complex, (Cs)[Ag(CF 3 )] 2 and CuI (Scheme 23).…”