Trifluoromethylated optically active

Table V Diastereoselective Cyclopropanation with Trifluoromethylated Optically Active Ally lie Alcohols...

Facile synthesis of optically active trifluoromethylated compounds asymmetric Diels-Alder reaction of trifluoromethylated ot, -unsaturated sulfonamide under high-pressure conditions [79]... 

It is interesting to note that asymmetric induction was also observed (308) during generation of ylide 288 from achiral sulfonium salt 287a by means of chiral lithium 2,2,2-trifluoromethyl-a-phenylethoxide. The [2,3]sigmatropic rearrangement of the chiral ylide 288 obtained in situ in this way leads to optically active sulfide 289 of 5% optical purity. 

The synthesis of 2-(trifluoromethyl) derivatives is more difficult and the compound preferentially obtained depends on the substituents and on the reaction conditions. Thus, the reaction of tryptophan with TFAA gives the 5(47/)-oxazolone without racemization." However, when this optically active product is dissolved in acetonitrile the racemic 5(47/)-oxazolone is obtained. On the other hand, treatment of the optically active compound with hot aqueous dioxane gave the isomeric 5(27/)-oxazolone (see Scheme 7.2). 

The nature of the intermediate cationic species, whether it is a classical methyl cation or a nonclassical bridged cation, has also been determined. The deamination of optically active e c/o-2-aminobicyclo[2.2.1]hcplane-exo-2-carbonitrile gave 2-hydroxybicyclo[3.1. l]-heptane-1-carbonitrile (19) in 9% yield with 92% retention of the optical activity. Similarly, deamination of e.vo-2-trifluoromethylbicyclo[2.2.1]heptyl-e Jo-2-amine gave 1-trifluoromethyl-bicyclo[3.1.1]heptan-2-ol (20) in 11 % yield with 88% retention of the optical activity. These results are interpreted in terms of intermediate bridged cations.87... 

The authors have also investigated the absolute configuration of optically active carbinols with a trifluoromethyl group. The synthetic strategies employed are shown in Scheme 1. The absolute stereochemistry of the synthetic intermediate... 

Carbonyl Addition Diethylzinc has been added to benzaldehyde at room temperature in the presence of an ephedra-derived chiral quat (8) to give optically active secondary alcohols, a case in which the chiral catalyst affords a much higher enantioselectivity in the solid state than in solution (47 to 48, Scheme 10.6) [30]. Asymmetric trifluoromethylation of aldehydes and ketones (49 to 50, Scheme 10.6 [31]) is accomplished with trifluoromethyl-trimethylsilane, catalyzed by a quaternary ammonium fluoride (3d). Catalyst 3d was first used by the Shioiri group for catalytic asymmetric aldol reactions from silyl enol ethers 51 or 54 (Scheme 10.6) [32]. Various other 1,2-carbonyl additions [33] and aldol reactions [34] have been reported. 

Chiral crotonates derived from S-citronellol, l-(—)-menthol, and 5-solketol undergo 1,3-dipolar cycloaddition with cyclic and acyclic nitrones.66 Asymmetric 1,3-dipolar cycloaddition of optically active trifluoromethylated a, /i-unsaturated aryl sulfones (43) with nitrones yield the corresponding isoxazolidines (44) and (45) with high regio- and... 

Optically active lanthanide shift reagents such as tris-(3-trifluoromethyl-hydroxymethylene-( + )-camphorato) europium (4) are commercially available. They can be used for the direct determination of optical purity and for the measurement of enantiomeric composition. The differences in the lanthanide-induced shift between enantiomers can be as high as 1.8 p.p.m. depending on the geometry of the molecule. 

Sn2 reaction at a-carbon of trifluoromethyl group preparation of optically active 2-tri-fluoromethylaziridine. Tetrahedron Asymmetry 1997, 8, 2933-2937. 

Katagiri, T. Uneyama, K. Stereospecific substitution at a-carbon to trifluoromethyl group application to optically active fluorinated amino acid synthesis. Chirality 2003, 35, 4-9. 

The 5(2H)-oxazolones (213) present two sites, C(4) and C(5), to nucleophilic attack they usually react at the latter. The benzylidene derivative (214), the most thoroughly studied member of this class, possesses an additional electrophilic centre at the exocyclic carbon atom. However, alkaline hydrolysis of this compound affords phenylacetamide and benzoylformic acid by acyl-oxygen fission (equation 50). a-Keto acids are also obtained when 2-trifluoromethyl-5(4//)-oxazolones are hydrolyzed, the reaction involving preliminary isomerization to a 5(2//)-oxazolone. The example shown in equation (51) represents the first non-enzymatic synthesis of an optically active a-keto acid. An instance of nucleophilic attack at C(4) of a 5(2//)-oxazolone is the formation of the oxazolidinone (215) in a Grignard reaction (equation 52). However, the typical behaviour of unsaturated pseudooxazolones like (214) is conjugate addition of a nucleophile, followed by further transformations of the resulting 5(4F/)-oxazoIones. This is illustrated by the reaction of compound (214) with benzene in the presence of aluminum chloride to yield, after aqueous work-up, the acylamino acid (216 equation 53). 

Trifluoromethylation of enolates could be achieved by complexing the enolate with boron Lewis acids (Equation 118). The best boron Lewis acid for this purpose was 2-phenyl-l,3,2-benzodioxaborole 231. For enantio-selective trifluoromethylation, the optically active boron compound 232 was used (Equation 119). 

This reaction has also been applied to optically active trifluoromethylated a,/8-unsaturated sulfoncs. ... 

Candida antractica lipase B- and immobilised Mucor miehei lipase- catalysed alcoholysis and C-rugosa lipase- catalysed hydrolysis have been successfully used for the highly effective synthesis of optically active trifluoromethylated 1-and 2-hydroxyalkane-phosphonates (268) and (269) from their racemic O-acylated precursors (270) and (271) (Scheme 68). ... 

The Curtius rearrangement of the acyl azide derived from optically pure a-methoxy-a-(trifluoro-methyl)phenylacetic acid (MTPA 48) also proceeds with retention of configuration, giving a-methoxy-a-(trifluoromethyl)benzyl isocyanate (49 equation 26). The isocyanate (49) is useful for the determination of the enantiomeric composition of optically active primary and secondary amines. 

The reaction can be applied to amino acids if carried out in hydrogen fluoride, which serves to protect the amino group. If the amino acid is optically active, optical activity is retained. Thus L-leucine gives levorotalory 3-methyl-l-(trifluoromethyl)-butylamine. 

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