Alkenes trifluoromethyl

Syntheses of fluoro-substituted pyrazoles continue to be of interest. Both 3- and 5-fluoropyrazoles (44 and 45, respectively) can be prepared from 43 <96JOC2763>. Treatment of 43 with hydrazine followed by N-alkylation provides 44, whereas reactions with monosubstituted hydrazines afford 45. The 4-(trifluoromcthyl)pyrazoles 47 are obtained from J-trifluoromethyl vinamidinium salt 46 <96TL1829>. The 5-trifluoromethyl-3-carboethoxypyrazoles 49 are obtained from the 1,3-dipolar cycloadditions of trifluoromethyl alkenes 48 with ethyl diazoacetate <96T4383>. 

Treatment of difluoroallylic alcohols with sulfur(II) or phosphorus(III) halides resulted in [2,3]-rearrangement (Eq. 135) under mild conditions [349]. This method constitutes a potential alternative route to difluorophosphonates, and to difluorosulfoxides and sulfones. The Jussieu group showed that thionyl chloride or bromide converted difluoroallylic alcohols to the corresponding halodi-fluoromethyl allylic compounds (Eq. 136) [350]. Exposure to DAST afforded the trifluoromethyl congeners [351, 352] and Kumadaki showed that /i-chloro-y,y-difluoroallylic alcohols afforded the trifluoromethyl alkene products upon treatment with HF. 

The anti-SN2 substitution of allylic aziridines (see Section 10.5.2.1.3.2) has been extended to the synthesis of the methyl-substituted D-Ala-Ala alkene isostere 153 (Scheme 33)J91 For the corresponding (trifluoromethyl) alkene isostere, the aziridine precursor could not be formed. Instead, allylic SN2 displacement (see Section 10.5.2.1.3.1) of the mesylate 154 occurred readily to provide the Ala-D-Ala isostere 155. 

Table 21. l,l-BLs(trifluoromethyl)alkenes Prepared from Hexafluoroisopropylidenetriphenylphosphorane [5[Pg.590]

A convenient method for the synthesis of l,l-bis(trifluoromethyl)alkenes 13 from aldehydes and 2.2-dichlorohexafluoropropanc in the presence of triphenylphosphane has been developed. ... 

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. 

With 1,1-disubstituted trifluoromethylated alkenes, such as a-(trifluoromethyl)styrene, cycloaddition w ith nitrone 1 is regioselective, and a 50 50 mixture of the ais/ /ranj-isomers is obtained, as observed in Diels-Alder cycloaddition reactions (see Section 2.1.1.6.2.1.1.).5 When the reaction is performed solvent-free under microwave irradiation, instead of under thermal conditions (boiling toluene), the yield is improved from 65% to 98% and the reaction time decreases from 48 hours to 4 minutes, however, stereoselectivity is not improved.79... 

Wipf, P., Henninger, T. C. and Geib, S. J. (1998) Methyl- and (trifluoromethyl)alkene peptide isosteres synthesis and evaluation of their potential as P-tum promoters and peptide mimetics. J. Org. Chem., 63, 6088-6089. 

In 1998, Wipf and co-workers demonstrated that the replacement of a peptidic amide bond with a trifluoromethylated alkene mimics well the P-turn structure of the original peptide [7]. AMI-calculated dipolar moments of the amide bond and various alkene isosteres suggested the electrostatic similarity between the amide and the trifluoromethylalkene functionalities (see Figure 10.17) [7]. 

Synthetic applications of dithietane 35 are not limited to its use as a source of hexafluorothioacetone. This compound is also a valuable precursor for the synthesis of a variety of fluorinated sulfur-containing derivatives. For example, the pyrolysis of 35 at 325 C results in the high-yield formation of (CF3)2C=C(CF3)2. The reaction of 35 with PhaP was found to be a convenient route to (Ph)3P=C(CF3)2, which was used for the preparation of l,l-bis(trifluoromethyl) alkenes and CF2=C(CF3)P(0)(0R)2. Recently reported transformation of fluorinated thietanes involves reductive ring expansion to substituted dihydrothiophenes. For example, the treatment of compound 47 with aluminum powder in the presence of a catalytic amount of PbCl2 resulted in an interesting ring expansion process leading to the formation of compound 48 in excellent yield (Scheme 2.23). Readily available fluorinated cycloadducts 49... 

Polyfluoroalkoxylation of aromatic rings has been achieved by SnAt reactions of dinitrobenzenes with polyfluoro alcohols in the presence of excess TBAF (eq 51). Finally, TBAF-assisted Homer-Wadsworth-Emmons reactions provide a convenient entry into trifluoromethylated alkenes (eq 52). 4... 

Fig. 2 Proposed reaction mechanism for the synthesis of trifluoromethylated alkenes from potassium vinyltrifluoroborates by photoredox catalysis. Reproduced from ref. 87 with permission from The Royal Society of Chemistry.

A full account of the synthesis of the mercurials PhHg-CXCI-CF, (X = Br or Cl) and their plications in synthesis as direct thermal sources of chloro(trifluoromethyl)carbene (Vol. 1, p. 87) is also available now. The bromide (X = Br) is the preferred reagent since it decomposes at a lower temperature (used at 130—140 °C) than the chloride (X = Cl slow at 160 C), and examples of its use in the preparation of 1-chloro-l-(trifluoro-methyl)cyclopropanes, l-chloro-2,2,2-trifluoroethylsilanes (see p. 197), and l-chloro-l-(trifluoromethyl)alkenes [PhHgCBrCICFs... 

The addition of azomethine ylides 102 formed by heating of the aziridines 77a,b (R=t-Bu) to the trifluoromethylated alkenes 103 led to mixtures of the diastereomeric pyrrolidines 104 and 105. Subsequent elimination of HF by treatment with sodium methoxide in methanol gave predominantly the pyrrole 106 and minor amount of the regioisomer 107 [43]. 3,4-Bis(trifluoromethyl)pyrrole 108 with a free nitrogen atom was obtained using iV-trimethylsilyl aziridine 77c [48],... 

As mentioned in the previous section, trifluoromethylated alkenes are promising building blocks for pharmaceuticals, agrochemicals, and functional materials [112-116]. But reported synthetic methods via trifluoromethylation exhibited limited substrate scopes with respect to hetero-aromatics and functional groups [117-121]. We found that application of potassium vinyltrifluoroborates 23, which are regarded as electron-rich alkenes, to our photocatalytic oxytrifluoro-methylation leads to efficient formation of trifluoromethylated alkenes 24 via deboronation. We revealed that our photoredox-catalyzed protocol for construction of Caikenyi-CF3 bonds exhibits broad scope in an efficient and stereoselective manner. 

Photoreaction often provokes an issue of scalability because efficient reaction requires a transparent reaction system. As a demonstration of scalability of the present reaction, the trifluoromethylation of 23h was carried out on a gram scale (Scheme 19). As a result, the trifluoromethylated alkene with quinoline moiety 24h, which is a herbicide-related molecule [116], was obtained in a good yield (64%, 1.06 g) with an excellent /Z selectivity (>99/[Pg.388]

Scheme 20 A plausible mechanism for -selective formation of trifluoromethylated alkenes...

Work on the synthesis of l,l,l-trifluoro-2-trifluoromethylpenta-2,4-diene from hexafluoroacetone has cast considerable doubt on an earlier claim regarding the preparation of this monomer. The successful method now reported involves dehydration of l,l-bis(trifluoromethyl)alken-l-ols obtained from hexafluoroacetone and propene (c/. p. 75), e.g. 

Although several reviews have been published regarding the preparation of trifluoromethylated molecules, there seems to be none dealing specifically with the synthetic methods for the preparation of substances bearing a CF3 group at the multiple bond. This review especially concerns the stereoselective preparation of trifluoromethylated alkenes 1 and allenes 2 as shown in Rgure 26.1.Trifluoromethylated alkynes 3 as well as aromatics 4 are also included to some extent in this review. 

CFa-attached heteroaromatics can easily be synthesized as well. Very importandy, trifluoromethylated alkenes, of which diere have been limited studies on the direct synthetic methods, can participate very well in the cross coupling, although a decrease of the yields can be observed and in addition the alkenes are partially isomerized during the reaction. 

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