Trifluoropyruvate ethyl

Excellent enantioselectivity has also been obtained using 3,3 -6 s-(l-naphthyl) BINOL-phosphoric acids [311]. A -Tosyl imines of aryl aldehydes were also examined using a binaphthyl Pd(II) carbene complex as the catalyst. Enantioselectivity in the 50-75% range was obtained [312]. Imines formed from ot-phenylethylamine and ethyl 3,3,3-trifluoropyruvate give adducts with 85-97% de in the presence of TEA [313]. The chiral auxiliary can be removed by hydrogenolysis. 

To a sealable glass reaction vessel under inert atmosphere containing 5-methylindole (0.5 mmol) and cinchonidine (102, 0.0375 mmol) was added 3 mL anhydrous Et20. The solution was stirred at -8 °C (salt-ice cooling bath) for 30 min. Then 0.75 mmol ethyl 3,3,3-trifluoropyruvate was added, and the mixture was stirred at -8 °C (salt-ice cooling bath) for 3 h. The mixture was concentrated with removal of the solvent and excess ethyl trifluoropyruvate... 

Trifluoroalanine has also been prepared by reducing trifluoropyruvate imines (ethyl trifluoropyruvate is available commercially it is prepared either from per-fluoropropene oxide or by trifluoromethylation of ethyl or f-butyl oxalate). These imines are obtained by dehydration of the corresponding aminals or by Staudinger reaction. They can also be obtained by palladium-catalyzed carbonylation of trifluoroacetamidoyl iodide, an easily accessible compound (cf. Chapter 3) (Figure 5.4). Reduction of the imines affords protected trifluoroalanines. When the imine is derived from a-phenyl ethyl amine, an intramolecular hydride transfer affords the regioisomer imine, which can further be hydrolyzed into trifluoroalanine. ... 

Trifluorovinylstannane has been successfully employed in the Stille crosscoupling reaction with aryl or vinyl halides in the presence of a palladium catalyst [190, 191] (Scheme 68). Recently, ethyl 3-(tributylstannyl)-2-methoxyacrylate was prepared from ethyl trifluoropyruvate in several steps and used in the Stille reaction for the synthesis of a-fluoro-keto acid derivatives [192] (Scheme 69). 

Uneyama has described some interesting reactions of the N-aryl imines of ethyl trifluoropyruvate. Tandem alkylation/defluorination occurred (Eq. 97) upon exposure to diethylzinc, via attack at nitrogen and SN2 displacement of fluoride anion [279]. Interestingly, an alkylzinc halide reagent attacked regioselec-tively at carbon, perhaps the more expected outcome. 

Prakash, Olah, and co-workers256 have prepared Mosher s acid analogs by the hydroxyalkylation of substituted benzenes with ethyl trifluoropyruvate [Eq. (5.95)]. Deactivated aromatics (fluorobenzene, chlorobenzene) required the use of excess triflic acid indicative of superelectrophilic activation.3 5 In contrast to these observations, Shudo and co-workers257 reported the formation gem-diphenyl-substituted ketones in the alkylation of benzene with 1,2-dicarbonyl compounds [Eq. (5.96)]. In weak acidic medium (6% trifluoroacetic acid-94% triflic acid), practically no reaction takes place. With increasing acidity the reaction accelerates and complete conversion is achieved in pure triflic acid, indicating the involvement of diprotonated intermediates. 

Bravo et al. treated (Ss)-(+)-p-toluenesulfinamide (63), prepared by hydrolysis of 44,23 with triphenylphosphine in the presence of DEAD to give the N-sulfinyl iminophosphorane 64 in 92% yield.45 The Staudinger, aza-Wittig reaction of 64 with methyl or ethyl trifluoropyruvate afforded the unstable sulfinimine 65. Attempts to purify the imino sulfinimines by flash chromatography resulted in hydrolysis. 

The TiCl4-catalyzed reaction of A-acyloxazolidin-2-thione 2 (see Scheme 4.1) with ethyl trifluoropyruvate 3 afforded two diastereomeric adducts 4 and 5, out of four possibilities, in low diastereomeric ratio. The reaction features a favorable scale-up effect, affording -70% yield on a hundred-milligram scale, and 90% on a ten-gram scale. Several alternative conditions were explored, but no improvement in diastereocontrol was achieved. 

Oxazolidine 144 obtained from amino alcohol 143 and ethyl trifluoropyruvate is also a synthetic intermediate for 2-amino-2-trifluoromethylpentanoic acid 145. Lewis acid-catalyzed allylation of 144 with allyl silane occurs in excellent yield with a moderate stereoselectivity. Meanwhile, O-tert-butyldimethylsilyl-protected imine 146 gives better diastereoselectivity although yield is poor (see Scheme 9.31) [57]. 

Chaume, G., Van Severen, M-C., Marinkovic, S. and Brigaud, T. (2006) Straightforward synthesis of (S)- and (W)-a-tri II uoromclhyl proline from chiral oxazolidines derived from ethyl trifluoropyruvate. Org. Lett., 8, 6123-6126. 

Simple esters did not lead to addition products. However, the Barbier procedure was effective, even at atmospheric pressure, when the ester was activated by an electron-withdrawing group ethyl trifluoropyruvate and hexafluoroacetone were respectively obtained from diethyl oxalate and ethyl trifluoroacetate (Fig. 9). 

For many years now, the reactivity of trifluoromethyl bromide has been underestimated. During the past decade the major breakthrough in this area has been the realisation that trifluoromethylation of organic compounds with this halide can be induced by mild reductants such as thiolates, zinc or sulfoxylate radical anion. Nowadays, a great variety of fluorinated products are available by these new methods sodium triflinate and triflic acid, trifluoromethylated alcohols, trifluoromethyl-containing aromatic compounds, ethyl trifluoropyruvate, trifluoromethylsulfides. ... 

Ene reaction of 26 with ethyl trifluoropyruvate (29) proceeded with high enan-tioselectivity using the dicationic Pd catalyst prepared by the reaction of SEGPHOS (XIV-3)-PdCl2 with AgSbFg to give 30 with 96% ee quantitatively [8]. 

The most challenging combination for this transformation is the use of an aldehyde as source of nucleophUe and a ketone as electrophile. This reaction has been successfully achieved by using several aldehydes 5 with high electrophilic ketones (38), such as diethyl ketomalonate or ethyl trifluoropyruvate, in the presence of... 

Ethyl trifluoropyruvate has been activated in TfOH medium for the hydroxyalkylation of arenes to give valuable Mosher s acid derivatives in good to excellent yields. Even Selectfluor has been activated in TfOH to effect electrophilic fluorination of arenes including fluorobenzene and chlorobenzene. ... 

Sokolov VB, Aksinenko AY, Martynov IV (2001) Reaction of 6-amino-1,3-dimethyluracil with hexafluoroacetone and ethyl trifluoropyruvate benzoyUmines. Russ Chem BuU 50 1113-1114... 

In order to create a novel class of acaricide and insecticide, a series of 2-substituted-3-TFQ were synthesized by utilizing ethyl trifluoropyruvate as a novel source for CF3 moiety, and acaricidal and insecticidal activity were determined. 

N-Boc-protected ethyl trifluoropyruvate imine was effectively used in a F-C reaction with indole derivatives for synthesizing, in high selectivities, quaternary a-amino acids via catalysis with chiral phosphoric acid 26e [64]. A binaphthyl-based chiral sulfonimide [42c] and a chiral squaramide-based hydrogen bond donor [42a] were used as effective catalysts for promoting F-C reaction of indoles with imines. Recently, the F-C alkylation of arenes with glyoxylate imine was described via a chiral phosphoric add (Scheme 35.11) [34]. 

Bolm et al. have developed a highly enantioselectlve Friedel-Crafts reaction of A-Boc-protected ethyl trifluoropyruvate imlne (289) with a wide variety of indole derivatives (288) catalysed by the chiral phosphoric acid (253) to afford quaternary a-amino acids (290) in excellent yields (up to 99%) and high enantioselectivities (up to 98 2 er) (Scheme 75). ° ... 

An asymmetric intermolecular carbonyl-ene reaction catalyzed by 1 mol% of chiral A-triflyl phosphoramide (/ )-4t (1 mol%, R = 4-MeO-CgH ) was developed by Rueping and coworkers (Scheme 69) [88], Various a-methyl styrene derivatives 163 underwent the desired reaction with ethyl a,a,a-trifluoropyruvate 164 to afford the corresponding a-hydroxy-a-trifluoromethyl esters 165 in good yields along with high enantioselectivities (55-96%, 92-97% ee). The presence of the trifluoromethyl group was crucial and the use of methyl pyruvate or glyoxylate instead of 164 resulted in lower reactivities or selectivities. 

Scheme 69 Carbonyl-ene reaction of a-methyl styrenes and ethyl a,a,a-trifluoropyruvate...

Asymmetric hydrogenation of imines derived from trifluoropyruvate, in the presence of a chiral complex of palladium (ligand = (R)-BINAP), affords ethyl (/f)-trifluoroalaninate with ca. 90% The ee values strongly depend on the solvent,... 

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