Aldehydes unsaturated trifluoromethyl

Abele, H., Haas, A., and Lieb, M., Efforts in synthesizing a,P-unsaturated trifluoromethyl-substituted aldehydes, Chem. Ber, 119, 3502, 1986. 

The organocatalysed asymmetric cycloaddition reaction of a,p-unsaturated ketones and aldehydes is scarcely studied, especially for fluorine-containing substrates. In this area, Liu et al. have reported unusual inverse-electron-demand oxa-Diels-Alder reactions of a,p-unsaturated trifluoromethyl ketones with aldehydes catalysed by chiral a,a-diphenylprolinol trimethylsilyl ether. It was shown that the addition of pura-fluorophenol and silica gel along with this catalyst was necessary, otherwise the reaction was very slow and a poor yield was obtained. Under these optimal conditions, the expected cyclic adducts were obtained in good yields and high fl n-diastereo- and enantioselectivities, as shown in Scheme 6.11. 

Inverse-electron-demand hetero-Diels-Alder reaction of enolizable aldehydes with a,P-unsaturatedketophosphonates [27], o-quinones [28], a-keto-a,p-unsaturated esters [29], a,P-unsaturated trifluoromethyl ketones [30], and o-benzoquinone diimide [31] was also reported. 

To overcome these problems with the first generation Brmsted acid-assisted chiral Lewis acid 7, Yamamoto and coworkers developed in 1996 a second-generation catalyst 8 containing the 3,5-bis-(trifluoromethyl)phenylboronic acid moiety [10b,d] (Scheme 1.15, 1.16, Table 1.4, 1.5). The catalyst was prepared from a chiral triol containing a chiral binaphthol moiety and 3,5-bis-(trifluoromethyl)phenylboronic acid, with removal of water. This is a practical Diels-Alder catalyst, effective in catalyzing the reaction not only of a-substituted a,/ -unsaturated aldehydes, but also of a-unsubstituted a,/ -unsaturated aldehydes. In each reaction, the adducts were formed in high yields and with excellent enantioselectivity. It also promotes the reaction with less reactive dienophiles such as crotonaldehyde. Less reactive dienes such as isoprene and cyclohexadiene can, moreover, also be successfully employed in reactions with bromoacrolein, methacrolein, and acrolein dienophiles. The chiral ligand was readily recovered (>90%). 

Another general method for the preparation of 19,19,19- and 20,20,20-trifluor-oretinals involves the aldol condensation of trifluoroacetone with an ethylenic aldehyde. When performed in the presence of acetic acid and piperidine, it affords an a, S-unsaturated ketone. Applied to cyclocitral and its homologues, the method leads to polyenic trifluoromethyl ketones. From these ketones, the various tri-fluorinated retinoids are prepared by known methods (Figure 4.24). ... 

In similar work, CF3CC12C02CH3 yields methyl a-trifluoromethyl-o<, )-un-saturated carboxylates when reacted with a zinc-copper couple, aldehydes, and acetic anhydride [67] (equation 55). This methodology gives (Z)-a-fluoro-a- -unsaturated carboxylates from the reaction of carbonyl compounds with CFCI2CO2CH3 and zinc and acetic anhydride [68],... 

A hetero Diels-Alder reaction of a,[)-unsaturated ketones or aldehydes with, V,A,-dibuty 1(3,3,3-trifluoro-l-propynyl)-amine 100 affords 2-(dibutylamino)-3-(trifluoromethyl)-4//-pyrans in good yield (Equation 51). However, 3-methoxy and P-phenyl-a,()-unsaturated ketones fail to react under these conditions (Equation 51) <2000CL666>. 

The effectiveness of the 1,1.1-trichlorotrifluoroethane/triphenylphosphane system in reactions with aldehydes, which lead to the formation of (trifluoromethyl)alkenes, has been demonstrated. The reaction with aromatic and a,) -unsaturated aliphatic aldehydes proceeds with high stereoselectivity (the Z-isomcr is formed exclusively), whereas the reaction with other aliphatic aldehydes affords a mixture of the Z- and /T-isomers in proportions ranging from 2 1 to 3 1. 

Alkyl, aryl, and unsaturated aldehydes can be transformed to the corresponding x-trifluoro-mcthylated alcohols in 86-96% yield by trifluoromethylation of the aldehydes with sodium triethylgermanidc/phenyl trifluoromethyl sulfide.75... 

The first example of preparation of an a,P-unsaturated aldehyde from unprotected 1-formylmethylphosphonate involved the rather reactive substrate hexafluoroacetone. Thus, diethyl 1-formyhnethylphosphonate reacts with hexafluoroacetone in n-BujO at room temperature in the presence of t-BuOK to give the 3,3-Z /i(trifluoromethyl)propenal in 54% yield. " " Another example describes the formation of an aji-unsaturated aldehyde in 62% yield from unprotected 1-formyhnethylphosphonate under Masamune conditions (LiCl, DIE A, MeCN, room temperature).3" ... 

The solubility of the catalyst salt is improved by the use of 3,5-bis(trifluoromethyl)phenylborate or triflate anions. Unsaturated fatty acids can be reduced in the same way.173 Hydrogenations in sc carbon dioxide can be more selective than in the gas phase while using 35 times less catalyst.174 Cyclohexene was reduced with hydrogen and a polysilox-ane-supported palladium catalyst in in a continuous-flow reactor in 95-98% yields. Epoxides, oximes, nitriles, aldehydes, ketones, and nitro compounds can also be reduced. By varying the temperature, the products from the reduction of nitrobenzene can be selected from aniline, cyclo-hexylamine, dicyclohexylamine, and cyclohexane. In the... 

Unusual reactivity of hydrazones containing trifluoromethyl group with unsaturated aldehydes was exploited by Rueping. These components under the catalysis of a Bronsted acid and catalyst C2a afforded [3 + 3] anulation. The reaction afforded chiral trifluoromethylated dihydropyr-idazines (Scheme 8.30). 

Scheme 8.30 Reaction of trifluoromethyl hydrazones with unsaturated aldehydes.

Keywords a,p-Unsaturated aldehydes, ( )-l-phenyl-2-(2,2,2-trifluoroethylidene), PTSA, toluene, room temperature, electrocyclic/sigmatropic rearrangement, 3-trifluoromethyl-l,4-dihydropyridazines... 

Ishihara and coworkers have demonstrated that fluorinated alkynylamines (112) react smoothly with a variety of aldehydes or ketones, in the presence of a catalytic amount of Bp3 OEt2 and of 4A molecular sieves, to give the corresponding a-(trifluoromethyl)-a,P-unsaturated amides (113) in good yields and high Z E selectivity (Equation 68) [71]. 

On the other hand, trifluoromethylated ynamines can be prepared in three steps, starting from pentafluoropropanol (Scheme 26.52). Thus, obtained ynamines can react with various aldehydes as well as ketones in the presence of 10 mol% of BF3 OEt2 and MS 4 A in CH2CI2 at room temperature to afford a-trifluoromethyl-a,(3-unsaturated amides in good to high yields.When aldehydes are used as carbonyl compounds, (Z)-a,(3-unsaturated amides... 

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