Trifluoroacetaldehyde ethyl

Indole has also been demonstrated to undergo a thermally induced condensation with trifluoroacetaldehyde ethyl hemiacetal to give a variety of products depending on the reaction conditions, e.g., the 6,12-dihydroindolo[3,2-f)]carbazole 172, which could be isolated in low yield from the mixture originating from the heating of equimolar amounts of the reactants in the absence of solvent. The formation of an intermediate indolenine species was suggested to account for the outcome (88JFC47). 

The indium-mediated allylation of trifluoroacetaldehyde hydrate (R = H) or trifluoroacetaldehyde ethyl hemiacetal (R = Et) with an allyl bromide in water yielded a-trifluoromethylated alcohols (Eq. 8.56).135 Lanthanide triflate-promoted indium-mediated allylation of aminoaldehyde in aqueous media generated (i-airiinoalcohols stereoselectively.136 Indium-mediated intramolecular carbocyclization in aqueous media generated fused a-methylene-y-butyrolactones (Eq. 8.57).137 Forsythe and co-workers applied the indium-mediated allylation in the synthesis of an advanced intermediate for azaspiracids (Eq. 8.58).138 Other potentially reactive functionalities such as azide, enone, and ketone did not compete with aldehyde for the reaction with the in situ-generated organo-indium intermediate. 

When trifluoroacetaldehyde ethyl hemiacetal [F3CCH(OH)OEt] is treated with enamines in hexane at room temperature, it provides a source of the aldehyde under mild conditions. Subsequent reaction with the enamine can be used to prepare -hydroxy-/ -trifluoromethyl ketones, F3CCH(OH)CH2COR. The enamine plays successive roles as base, ammonium counterion, and then carbon nucleophile as the sequence proceeds. 

Table 1. Thermal Condensation of Substituted Imidazoles with Trifluoroacetaldehyde Ethyl Hemiacetal [5]...

L-Proline catalyses direct aldols of trifluoroacetaldehyde ethyl (hemi)acetals, F3C-CFl(OH)-OX (X = H, CH2CH3, CH2CF3), with ketones at room temperature to produce /Miydroxy-/9-fluoromethylated ketones with des up to 96% and ees up to 91 %.97... 

A, heated at reflux with equimolar amount of trifluoroacetaldehyde ethyl hemiacetal, B, heated in a sealed tube (oil bath, 150-155 °C) with equimolar amount of tnfluoroacet-aldehyde ethyl hemiacetal... 

In the presence of catalytic amounts of anhydrons potassinm carbonate, phenols react with trifluoroacetaldehyde ethyl hemiacetal to give the / ara-alkylated prodncts (C-aUcylation of the phenolate anions). Thns, phenol nnder these conditions gives 4-(2,2,2-trifluoro-l-hydroxyethyl)phenol as the predominant prodnct. The reaction catalyzed by zinc halides predominantly gave the ortto-snbstitnted prodnct (eqnation 4) . ... 

Carbonyl compounds in certain protected forms such as gcm-diacetates" and hemiac-etals (e.g., trifluoroacetaldehyde ethyl hemiacetal ) also undergo allylation, giving in these cases homoallylic acetates and homoallyl alcohols, respectively. 

SFs-anilines, aldehydes, and arylacetylenes (15EJ01415). This method was inspired by the Fe(III)-catalyzed aerobically oxidative synthesis of quinoHnes developed by Tu and coworkers (09CEJ6332). Both 3- and 4-SF5-anihnes (39 and 11), various aldehydes—aromatic, heterocyclic, formaldehyde, trifluoroacetaldehyde ethyl glyoxylate, and aromatic alkynes can serve as reaction components to provide access to a series of 2-aryl substituted 6(7)-SF5-quinolines 104a—s (Scheme 26). Flowever, cyclization products were not observed when aliphatic alkynes were used under the reported conditions. 

One of the popular and widely used methods for the synthesis of 2-trifluoromethylimidazole involves the Radziszewski reaction (Debus-Radziszewski reaction) [2a]. Following the Davidson s modifications (using ammonium acetate in acetic acid instead of ammonia in alcohol) [13a], Lombardino and Wiseman prepared a series of 2-trifluoromethylimidazoles via the condensation of a-dicarbonyl compounds and trifluoroacetaldehyde ethyl hemiacetal (Scheme 4) [13b]. The reaction presumably proceeds via the formation of a diimide intermediate that subsequently undergoes condensation with the aldehyde to afford the final product. An anhydrous condition is highly recommended for better yields of imidazoles. 

The condensation of l-phenyl-3,3,3-trifluoro-l,2-propanedione monohydrate with various aldehydes in the presence of ammoninm acetate afforded the corresponding 4-phenyl-5-trifluorDmethylimidazoles (Scheme 31) [44]. For the preparation of 2,5-bis(trifluoromethyl)imidazoles, trifluoroacetaldehyde ethyl hemiacetal was used in excess instead of the aldehydes. The prerequisite diketone, that was isolated as its monohydrate, was prepared from the corresponding ketone using SeOa-... 

Loh, T.-P. Li, X. R. (1996) A versatile and practical synthesis of a-trifluoromethylated alcohols from trifluoroacetaldehyde ethyl hemi-acetal in water, J. Chem. Soc., Chem. Commun., 1929-30. 

NCCCN+C approach was also used for the preparation of fused dihydropyrimidines. In particular, reaction of intines 668 with trifluoroacetaldehyde ethyl hemiacetal in the presence of acidic catalyst gave pyrimido[4,5-d]pyrimidine derivatives 669, although in low yields (14-28 %) (Scheme 139) [401],... 

Fig. 8.14 Sn/InCb or In-mediated allylation of trifluoroacetaldehyde ethyl hemiacetal.

Single crystals of difluoromethane bis(sulfinic acid) anhydride 17 were isolated, after the cesium salt 119 was stored in the presence of traces of water vapor for several weeks <1998JFC(89)55>. Treatment of difluoromethane-l,l-bis(sulfonyl fluoride) 120 with liquid ammonia led to the formation of the cyclic ammonium imide 121 <1997ZNB359, 1997WO9731909>, while reaction of sulfamide 122 with trifluoroacetaldehyde O-ethyl hemiacetal afforded the cyclic aminal 60 (Scheme 41) < 1999S1731 >. 

Xanthates have been used most frequently because they offer the best combination in terms of reactivity, stability, and accessibility. Potassium 0-ethyl xanthate is commercially available and cheap. It is an excellent nucleophile and many xanthates can be made trivially by displacement of a suitable leaving group. The examples of radical additions displayed in Scheme 3 are representative and underscore many of the desirable features discussed above. As can be seen, the xanthate reagent is readily made from the hemiacetal of trifluoroacetaldehyde and adds efficiently to a large assortment of olefins [7]. 1,2-Dichloroethane was used as the solvent but many other solvents can be used. Several related trifluoromethylated xanthates have been prepared and can be used to introduce a trifiuoromethyl group into a complex molecule or to prepare various fiuorinated starting materials [8-10]. 

Cyclohexylpropionic acid was deprotonated with 2.2 equivalent of lithium diisopropylamide and the resulting dianion was condensed with trifluoroacetaldehyde which was generated in situ from its ethyl hemiacetal. The P-hydroxy acid 1 was isolated as a racemic mixture of two diastereomers. Silylation with tert-butyldimethylsilyl triflate was followed by ester hydrolysis to give the acid 2. A Curtius rearrangement with diphenylphosphoryl azide in the presence of benzyl alcohol afforded the protected P-amino alcohol 3 which was used in the preparation of the trifluoromethyl alcohol I. Oxidation using the Dess-Martin periodinane reagent (9) yielded the trifluoromethyl ketone II as a mixture of diastereomers. The signal for the carbonyl carbon in the 13C-NMR spectrum of this ketone appeared at 94.5 ppm and this is consistent with the hydrated form of the trifluoromethyl ketone. 

Further improvements resulted from the use of a probe for sonication.325 Jhe higher reactivity seems not to be due to an increased surface area, but rather to morphological and composition changes, as evidenced by electron microscopy and sputtered neutral mass spectrometry.i< When applied to ethyl bromo propionate and trifluoroacetaldehyde, the resulting p-hydroxy esters are obtained in good yields with predominance of the threo isomer.272... 

The products from addition of cyanide to aldehydes and ketones are often versatile substrates that lend themselves for further transformations to useful compounds. The early use of the dangerous HCN gas for this cyanohydrin formation could be circumvented by using TMSCN instead, as discovered by Evans etaL [43, 44). Loh et al subsequently reported the first adaptation of the TMSCN addition to aldehydes and ketones in water using Inp3 as the Lewis acid catalyst, with success even for trifluoro ethyl hemiacetal, the commercially available form of trifluoroacetaldehyde [45] (Figure 8.22). However, this procedure is not successful for ketones. 

---