Ruppert-Prakash reagent

In 1994, the first enantioselective trifluoromethylation reaction was achieved with the Ruppert-Prakash reagent, TMSCF3, in the presence of the cinchona-based quaternary ammonium fluoride 140 [65]. The chiral induction can arise from the dual activation mode of the catalyst, that is, the fluoride anion acts as the nucleophilic activator of (TMS)CF3 and the chiral ammonium cation activates the carbonyl group of 141. However, the observed ee values of the obtained carbinols 142 do not exceed 51 % and decrease considerably when nonaromatic carbonyl compounds (15% ee for R1 = n-C7H15 R2 = H) are used, which implies that 7t-7t stacking interactions between the carbonyl compound and cinchoninium occur (Scheme 8.54). 

Carbazoles 292 and azaindoles were trifluoromethylated selectively to 294 under copper catalysis with the Ruppert—Prakash reagent in the presence of trimethyl borate, 1,10-phenanthroline, and KF as a base. This reaction is also applicable to a variety of other arenes and heteroarenes (140L4268). 

A short review examines nucleophilic trifluoromethylation of C=N bonds imines, hydrazones, and nitrones, together with iminium cations and azomethine imines, mainly focusing on the Ruppert-Prakash reagent, TMS-CF3. ... 

CBrF) with (20), respectively, led to the formation of (25) (and (26)) via a spontaneous ring opening of intermediate gem-dihalocyclopropanes (21) (and (22)) to form cations (23) (and (24)). The mechanism has been further supported by DFT calculations highlighting the exceptional stability of cations (23) and (24). Besides, Cp2 carbene generated from trimethyl(trifluoromethyl)silane (i.e., the Ruppert-Prakash reagent) has been shown to add smoothly not only to C=C but also C C bonds, thus furnishing valuable gem-difluorocyclopropanes and. gem-difluorocyclopropenes, respectively. ... 

Trimethyl(trifluoromethyl)silane (Me3SiCF3), commonly referred to as the Ruppert-Prakash reagent, serves as a trifluoromethyl anion equivalent, which is remarkable because of the instability of the anion with respect to decomposition to difluorocar-bene and fluoride ... 

Li and Mitsudera also describe the sjp C—H activation of THlQs but, in this case, introduce a trifluoromethyl group using DDQ and the Ruppert-Prakash reagent under mild conditions (Scheme 7.16). The Ruppert-Prakash reagent has been successfully used to provide alpha-trifluoromethylated amine derivatives this protocol provides a more direct and simpler synthetic pathway. 

The Ruppert—Prakash reagent [(trifluoromethyl)trimethylsilane] was employed to prepare N-substituted o-trifluoroacetylanilines 133, then subjected to a ring closure to give 9-trifluoromethylacridines 134 (2012 JFC272), Scheme 49. The trifluoromethyl-substituted acridines are of interest to medicinal chemists. 

A number of research groups have investigated the Cu-mediated conversion of C-B bonds in to C-CF3 groups. Clearly this has been driven by the ready availability of boronate starting materials. In 2010, Qing combined copper triflate with the Ruppert-Prakash reagent, KF and silver carbonate to effect the desired transformation. The conditions described display a broad scope of functional group tolerance (Scheme 15.97). 

In a novel approach, an enantiomerically pure derivative of 2-amino-4,4,4- trifluorobutanoic acid was synthesized via nucleophilic trifluoromethylation (Figure 3) (5). In the key step. Gamer s aldehyde (2) (6), an oxazolidine derived from L-serine, reacted with the Ruppert-Prakash reagent, TMS-CF3 (a trifluoromethide equivalent) (7) and tetrabutylammonium fluoride. (S) - 5,5,5,5, 5, 5 - Hexafluoroleucine (3) (88% ee) was prepared in 18% overall yield from hexafluoroacetone and ethyl bromopyruvate in seven steps (8). The highly enantioselective reduction of the keto carbonyl group of 4 to the hydroxyester 5 either by baker s yeast and sucrose (91% ee) or by catecholborane and an oxazaborolidine catalyst (99% ee) was the pivotal reaction of the sequence. These workers (9) also prepared (-)-(R)- 4,4,4,4, 4, 4 -hexafluorovaline (6) (98% ee). The key step was the separation of the tosylate salts of the diastereomers formed by anti-Michael addition of (+)-(R)-... 

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