Trifluoropyruvate imine

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. ... 

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]. 

Similarly, 1-alkylpyrroles, indoles, furans, thiophenes [60], a-picoline [61], enols, malonates [76], and organometallic compounds [56, 62] react with acyl imines of trifluoropyruvates to give derivatives of a-trifluoromethyl a-amino acids... 

A surpnsing feature of the reactions of hexafluoroacetone, trifluoropyruvates, and their acyl imines is the C-hydroxyalkylation or C-amidoalkylaOon of activated aromatic hydrocarbons or heterocycles even in the presence of unprotected ammo or hydroxyl functions directly attached to the aromatic core Normally, aromatic amines first react reversibly to give N-alkylated products that rearrange thermally to yield C-alkylated products. With aromatic heterocycles, the reaction usually takes place at the site of the maximum n electron density [55] (equaUon 5). 

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,... 

The acyl imines of methyl trifluoropyruvate react as heterodienes with electron-rich olefins in [4 + 2] cycloadditions, as exemplified by the synthesis of trifluoro-methyl aspartic acid (Figure 5.29). ... 

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. 

In the synthesis of hydroxamic acid 19a, having a free quaternary amino group (see Scheme 4.4), the intermediate sulfone 21 was synthesized by Pd-catalyzed reaction of phenol with p-bromo derivative 20 [24], Lithiation of 20, followed by nucleophilic addition to the A-Cbz imine of trifluoropyruvate 22 [25] afforded the a-CF3 a-amino acid derivative 23 in fair yields. Basic hydrolysis of the ester function gave the carboxylic acid 24, which was submitted to condensation with ()-15 n-hydroxylamine, affording hydroxamate 25. The subsequent hydrogenolysis of 25 afforded the target molecule 19a. 

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]. 

Base-catalyzed deprotonation-alkylation of trifluoroalanine is not easy because a-trifluoromethylated carbanions readily undergo defluorination in general [90]. Therefore, a-alkylated trifluoroalanines have been prepared either by alkylation of imines obtained from trifluoropyruvates [54, 57]or by Strecker cyanation [56] to trifluoroketimines fol-... 

Imines 299 of trifluoropyruvates are so strongly electrophilic that they undergo spontaneous ene-type carbon-carbon bond formation between 298 and 299 on their being mixed, as shown in Scheme 9.64. a-Trifluoromethylated tryptophan and its related amino esters 300 have been prepared (see Scheme 9.64) [95]. 

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. 

In 2001 Sokolov with co-workers extended the reaction to aminouracil. In a case of benzoyl imine 849 the reaction with nracil 925 gives C-aminoalkylated product 927 cyclized into fused pyrimidine derivative 928 (compare with amopyrazole behaviour, see Scheme 180). It should be noted, that similar sequence with imine of trifluoropyruvate 926 leads instead of 849 to pyrroIo[2,3-d]pyrimidine derivative 929 (Scheme 194) [559],... 

Addition of lithiated alkoxy ethynyl anion with chiral Al-sulfinyl imines proceeds with dr >95 5, which can be reversed in the presence of BF3. Excellent diastereoselec-tivity has been reported for zinc-mediated addition of methyl and terminal alkynes to chiral IV-f-butanesulfinyl ketimines (to form 3-amino oxindoles). Zinc-BINOL complexes have been used to achieve enantioselective addition of terminal alkynes to N-(diphenylphosphinoyl)imines (up to 96% cc) and terminal 1,3-diynes to IV-arylimines to trifluoropyruvates (up to 97% yield and 97% ee). ... 

The first section of this chapter describes the preparation and several synthetic applications of a-fluoroalkyl P-sulfmyl enamines and imines the second deals with the chemistry of di- and trifluoropyruvaldehyde A, 5-ketals, stereochemically stable synthetic equivalents of P-di and P-trifluoro a-amino aldehydes, which can be prepared from the corresponding p-sulfinyl enamines the third overviews the preparation of chiral sulfinimines of trifluoropyruvate and their use to prepare a library of a-trifluoromethyl (Tfm) a-amino acids the fourth section is mainly dedicated to the asymmetric synthesis of monofluorinated amino compounds, using a miscellany of methods such as MifstmobuAike azidation of P-hydroxy sulfoxides, ring opening of fluoroalkyl epoxides with nitrogen-centered nucleophiles and 1,3-dipolar cycloadditions with chiral fluorinated dipolarophiles. 

We decided to investigate the E wis aldol reaction (54,55) of the chiral a-hydroxy acetic anion equivalent 47 with the A -Cbz imine of trifluoropyruvate 33. Screening of several enolates and reaction conditions revealed that titanium enolate of the oxazolidinone 47, prepared with 1 equiv. ofTiCU and l.l equiv. of/-Pr2NEt, reacts with excellent stereocontrol affording the "Evans" syn diastereomer 48, in 88% isolated yield, having the correct stereochemistry to be used as intermediate for the synthesis of the targeted 2-Tfm-sphingolipids. 

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