TMSCF₃ as a Convenient Source of CF₂=CF₂ for Pentafluoroethylation, (Aryloxy)tetrafluoroethylation, and Tetrafluoroethylation

Abstract

An ew method for the on-site preparation of tetrafluoroethylene (TFE) and ap rocedure for its efficient use in pentafluoroethylation by fluoride addition were developed by using as imple two-chamber system. The on-site preparation of TFE was accomplished by dimerization of difluorocarbene derived from (trifluoromethyl)trimethylsilane (TMSCF 3 )u nder mild conditions.O ther fluoroalkylation reactions,s uch as (aryloxy)tetrafluoroethylation and tetrafluoroethylation processes,w ere also achieved using as imilar approach.T his work not only demonstrates ac onvenient and safe approach for the generation and use of TFE in academic laboratories,but also provides anew strategy for pentafluoroethylation.Organofluorine compounds are widely used as functional materials,a grochemicals,a nd pharmaceuticals owing to the unique physical, chemical, and biological features that result from fluorine substitution. [1] Therefore,d eveloping novel methods for the straightforward incorporation of per-o r polyfluorinated groups into organic molecules has received significant attention in both academia and industry. [2] Te trafluoroethylene (TFE, CF 2 =CF 2 ), as abulk fluorochemical for the industrial manufacture of poly(tetrafluoroethylene) and copolymers with other alkenes, [3] is an ideal C2 building block for incorporating fluorinated moieties such as -CF 2 CF 2 -, HCF 2 CF 2 -, and CF 2 = CF-into small molecules. [4] However, TFE is suspected to be carcinogenic, unstable towards radicals,a nd prone to explode when in contact with air,a ll of which in turn require that TFE gas is handled with extreme caution, including during storage and transport. [3d, 5] To overcome the inherent limitations associated with using TFE gas in academic laboratories,s everal TFE precursors have been developed that release TFE gas on site in small amounts.A vailable methods include the reduction of 1,2-dihalotetrafluoroethanes (XCF 2 CF 2 Y; X, Y = Br,Cl) with zinc powder [6] and the pyrolysis of sodium perfluoropropionate [3d] or poly(tetrafluoroethylene) [7] at high temperatures. However,t he restricted availability of XCF 2 CF 2 Ya nd the harsh conditions required for the pyrolysis reactions have limited the utilizations of these methods,thus preventing the development of fluoroalkylation reactions with TFE in common research laboratories.T herefore,t he development of practical and operationally simple methods for the laboratory preparation of TFE is highly desirable.TheRuppert-Prakash reagent (TMSCF 3 )isreadily available and is the most extensively used trifluoromethylation reagent for avariety of applications. [8] In 2011, our group and the Prakash group cooperatively developed an efficient method for the preparation of gem-difluorocyclopropa(e)nes by using TMSCF 3 as an ovel difluorocarbene source in the presence of NaI (Scheme 1a). [9] During the investigation, we noticed that TFE was normally formed as aside product (see the Supporting Information). [9a] In 2014, Baker and coworkers observed that am ixture of TMSCF 3 and NaI in THF cou...

CuI‐Catalyzed Pentafluoroethylation of Aryl Iodides in the Presence of Tetrafluoroethylene and Cesium Fluoride: Determining the Route to the Key Pentafluoroethyl CuI Intermediate

“…[20] In the crystal lattice, the Y-shaped coordination geometry of 2,w hich manifests in an N-Cu-N bond angle of 80.79(8)8,i sc onsiderably distorted, which is also reflectedi nt he C-Cu-N bond angles [147.28(10)8/131.64(10)8]a nd the CuÀNd istances [2.101(2) / 2.013(4) ], whereas the degree of distortion in 2 is slightly smaller than that observed in (bpy)CuC 2 F 5 (bpy = 2,2'-bipyridyl). [4h] In agreement with the report by Hu, [11] treatment of 2 with iodobenzene (3a)i nD MF at 60 8Cy ieldedp entafluoroethylbenzene (4a)i n8 5% yield (Scheme 2). In response to the result of the stoichiometricr eaction, our subsequent efforts were devoted to the development of aC u I -catalyzed pentafluoroethylation of iodoarenes in the presence of metal fluoride as as ource of fluoridea nions.…”

“…[10b] After our manuscript on this oxycupration chemistry was published online, we noted that, during roughly thes ame period,H ua nd co-workers had developed related( aryloxy)tetrafluoroethylation and pentafluoroethylation reactions, in which TFE was prepared in situf rom CF 3 SiMe 3 . [11] Although they demonstrated the related syntheticu tility of pentafluoroethylations employing TFE, special efforts to distinguish two possible routes to the key CuÀC 2 F 5 intermediates, that is, the fluorocupration of TFE [12,13] or the transmetalation between CsC 2 F 5 and copper(I) halide, [3b, 14] were not undertaken. In addition, applicationso ft hese Cu-catalyzed pentafluoroethylations were not carried out.…”

“…When iodobenzene 3a was employed, the catalytic reaction proceeded quantitativelyt oy ield 4a.T he use of electron-rich aryl iodides,s uch as p-tert-butyl-(3k), p-benzyloxy-(3l), and pmethoxy-iodoarene(3m), afforded the corresponding products (4k-m)i ne xcellent yield. In contrast, the reactions with p-iodoethylbenzoate (3n)a nd o-iodopyridine derivative (3o) proceeded sluggishly.I na ddition, the reactions with iodoarenes bearing an itro group (3p-r)p roceeded slowly,w hereasa stoichiometric treatment of 3p-r with in situ generated 2 resulted in the cleanf ormation of 4p-r. [11] In this catalytic system,t he electron-withdrawing group, especially the nitro substituent, might impede the regeneration of the key intermediates 1 and/or 2.M oreover,d iiodoarene derivatives (3s,t) could be employed as substrates for the preparation of bis-(pentafluoroethyl)arenes (4s,t), where an increased catalyst loading was required. When 2-bromo-8-iododibenzofuran (3u) was employed, 2-bromo-8-(pentafluoroethyl)dibenzofuran (4u) was obtained as the major product, albeit that trace amount of 4s were also detected duet oapentafluoroethylationo ft he C(sp 2 )ÀBr bond.…”

Deuteriodifluoromethylation and gem‐Difluoroalkenylation of Aldehydes Using ClCF2H in Continuous Flow

“…[22b,d] While literature precedents on the Wittig gem-difluoroalkenylation employed high reaction temperatures, [22c-e] we postulated that the enhanced heat transfer might also accelerate the dissociation of the ylide as well as dimerization of difluorocarbene to form tetrafluoroethylene. [23] We found that a decrease in temperature improved the reaction yields with 0 8C being the optimal (Table 1, entry 1-5). This is presumably due to the stabilization of the transient ylide.…”

From C1 to C2: TMSCF3 as a Precursor for Pentafluoroethylation

“…[5] Most of the current methods for the syntheses of pentafluoroethylated aromatic compounds use ac ertain C 2 F 5 source,b ut these reactions suffer from the following drawbacks:1 )not readily available,e xpensive or hard to handle C 2 F 5 sources;2 )harsh reaction conditions;3 )potentially explosive gaseous intermediate,a nd/or 4) low yields. [6][7][8][9][10][11][12] Owing to these problems,a ne fficient method for the synthesis of aromatic pentafluoroethyl compounds using ar elatively inexpensive,c ommercially available,e asy to handle reagent with simple manipulation is highly desired. TMSCF 3 ,n ow known as the Ruppert-Prakash reagent, has been the most widely used and versatile trifluoromethylation reagent for various substrates [2d,h,13] since its preparation by Ruppert et al [14] and application in nucleophilic trifluoromethylation by Prakash et al [15] Foralong time, TMSCF 3 was only considered atrifluoromethylation reagent (Scheme 1a,p ath a).…”