Trifluorocrotonate

The chemical shifts of trifluoromethyl groups at the terminus of a,(3-unsaturated carbonyl compounds are not affected by the presence of the carbonyl group, as is indicated by the examples in Scheme 5.37, and as exemplified by the fluorine NMR of 4,4,4-trifluorocrotonic acid, given in Fig. 5.14. 

Proton and Carbon Spectra of a -Unsaturated Carbonyl Compounds. Characteristic proton and carbon data for a,(3-unsaturated carbonyl compounds are provided in Scheme 5.38. Such spectra are exemplified by the proton and carbon spectra of 4,4,4-trifluorocrotonic acid in Figs. 5.15 and 5.16. 

The 1,3-dipolar cycloaddition of imidazolinone 123 with ethyl m-4,4,4-trifluorocrotonate 124 provided, after 36 h at reflux, the regio- and stereoisomer 125 (90%), accompanied with traces of three other unidentified cycloadducts (10%) <2001JFC275>. Compound 125 was isolated in 70% yield (Scheme 15). The structures of the final product were elucidated by nuclear Overhauser effect (NOE) experiments. This high selectivity is the result of a preferred ///////-orientation of both ester and CF3 groups in the transition state and of an impeded ////////-approach of the CFj-substituted terminus of the alkene to the sterically hindered ct-site of 123. 

The corresponding syzz-isomer was, on the other hand, prepared from the potassium permanganate-mediated oxidation of trifluorocrotonate 10, derived from -hydroxy-butyrate. In this procedure, the diol ester with syn relative configuration was the only product detected. After acetylation, syn-11 was employed as a substrate for the enzymatic resolution affording both (2S,3S)-11... 

FIGURE 5.18. HNMRspectrum of 4,4,4-trifluorocrotonic acid (vinylic area)... 

A solution of A -henzyl-C-ethoxycarbonyl nitrone (4 1.178 g, 5.7 mmol) and ethyl ( )-4.4,4-trifluorocroton-ale (0.958 g. 5.7 mmol) in toluene (40 mL) was refluxed for 5 h. The solvent was removed under reduced prcssurcand the residue was crystallized from hexane to givecompound6 yield 1.54g(72%) mp70 71 C. 

With 1,2-disubstituted alkenes, such as ethyl 4,4,4-trifluorocrotonate, 1,3-dipolar cycloadditions are not rcgiosclective and a mixture of 4- and 5-(trifluoromethyl)dihydroisoxazoles are obtained. ... 

Ethyl 4,4,4-trifluorocrotonate. 1,1-disubstituted fluoroalkenes and even trisubstituted fluoroalkenes readily react with nonstabilized azomethine ylides at room temperature to provide. in each case, only one regio- and stereoisomer 13 in high yield. 

Pyrrolidines obtained from trifluorocrotonates have been used to synthesize new fluoroquinolones. Starting from the trifluoromethyl analog of Hagemann s ester, it is possible to prepare a perhydroisoindolone with an angular trifluoromethyl substituent. ... 

The highly reactive ethyl ( ,)-4.4.4-trifluorocrotonate (5) reacts at room temperature with metalloazomethine ylides, generated from iniines of a-amino esters in the presence of silver salts, providing, in each case, one regio- and stercoadduct 12. The ester substituent governs this selectivity.98... 

Starting from ethyl 4, 4, 4-trifluorocrotonate, racemic aziridine carboxylic acid 96 was prepared as shown in Scheme 9.22 [46] and was then subjected to lipase-catalyzed esterification. Methyl ester 97 was obtained in 35% yield with excellent enantiomeric purity. Acid-catalyzed ring opening of aziridine 97 proceeded regio- and stereoselectively, affording 2-substituted (2R,3R) or (2/ ,3S)-3-amino-4,4,4-trifluorobutanoates 98 in high yields [47]. 

Addition of lithium enolate (56) to trifluorocrotonate (55) proceeded smoothly in almost quantitative yields with excellent stereoselectivity. The intramolecular chelation in 57 retards the retro-aldol reaction. On the other hand, nonfluorinated crotonate (59) provided 60 in a poor yield because of the faster retro-aldol reaction [26]. The stereochemistry of the chelated intermediate (57) was proven by trapping 57 as its ketenesilylacetal (61). Pd-catalyzed Ireland-Claisen rearrangement of 61 proceeded stereospecifically to give a single stereoisomer (62), suggesting a rigid control of the three consecutive stereocenters (Scheme 3.12) [27]. 

The corresponding syn-isomer was, on the other hand, prepared from the potassium permanganate-mediated oxidation of trifluorocrotonate 12, derived from... 

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