Olefins trifluoromethylation

Eeng C, Loh T-P (2012) Copper-catalyzed olefinic trifluoromethylation of enamides at room temperature. Chem Sci 3 3458-3462... 

Lastly, a-trimetfayisflyl enolates have been added to trifluoromethyl ketones to effect Peterson olefination of the tnfluoromethyl ketones [IS (equation 13)... 

Homer-Emmons reagents react with trifluoromethyl ketones to form tnfluo romethylated olefins, however, the double bond can isomerize out of conjugation with the carboxylic acid group with the product olefin that bears a y-proton [37] (equation 30)... 

Fluoride ion produced from the nucleophilic addition-elimination reactions of fluoroolefins can cataly7e isomerizations and rearrangements The reaction of per fluoro-3-methyl-l-butene with dimethylamine gives as products 1-/V,/Vdimeth-ylamino-1,1,2,2,4,4,4-heptafluoro-3-trifluoromethylbutane, N,W-dimetliyl-2,2,4,4,4-pentafluoro 3 trifluoromethylbutyramide, and approximately 3% of an unidentified olefin [10] The butylamide results from hydrolysis of the observed tertiary amine, and thus they share a common intermediate, l-Al,A -dimethylamino-l,l 24 44-hexafluoro-3-trifluoromethyl-2-butene, the product from the initial addition-elimination reaction (equation 4) The expected product from simple addition was not found... 

The phosphonium salt method works best with nucleophilic olefins [//, 12, 16, 17, 18, 19] (Table 1 and equations 1-3) and has been used m mechanistically important studies of difluorocarbene additions to norbornadienes [20 21, 22, 23] that provided the first example of a concerted homo-l,4-addition (equation 4) A recent modification uses catalytic 1,4,7,10,13,16 hexaoxacyclooctadecane (18-crown-6) to shorten reaction times and increase yields with less nucleophilic olefins [12] (Table 1) Neither procedure, however, compares with the use of phenyl(tri-f1uoromethyl)mercury or (trifluoromethyl)trimethyltin reagents [efficient reactions with less nucleophilic olefins (equations 3 and 5) and cyclic dienes [24, 25] (equations 6 and 7)... 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

Certain 1,5 diazabicyclo[3 3 0]oct-2-enes can be transformed unexpectedly into 4//-5,5-dihydro-l, 2 diazepines on heating [209] 1,5-Dipoles formed on heating of l,5-diazabicyclo[3 3 0]oct-2-enes [210] can be trapped with olefins to give [3+2] cycloadducts At elevated temperatures, they undergo a [3+2] cycloreversion Tins reaction sequence offers a simple route to dienes with interesting substitution patterns, for example, 1,1 bis(trifluoromethyl)-l,3-butadiene [211] The [3+2] cycloadducts that arise from the reaction of the 1,5 dipoles with acetylenes undergo... 

The fraction of head-to-head linkages in the poly(fluoro-olefms) increases in the series PVF2 < PVF PVF3 (Tabic 4.2). This can be rationalized in terms of the propensity of electrophilic radicals to add preferentially to the more electron rich end of monomers (i.e, that with the lowest number of fluorines). This trend is also seen in the reactions of trifluoromethyl radicals wilh the fluoro-olefins (see 2.3). 

If return occurs during the bromination of cw-stilbenes and rotation around the C-C bond is faster than collapse of the intermediates to dibromides, this process will lead to fra j-stilbene (Scheme 9). We used this test to check the possibility of return in the bromination of unsubstimted, 4-methyl, 4-trifluoromethyl-, and 4,4 -bis(trifluoromethyl)-stilbenes in DCE (ref. 24). All these olefins gave clean third-order rate constants spanning 7 powers of 10. For each cis-trans couple the cis olefin was brominated 3.5 to 5.5 times faster than the trans isomer. Reactions for products analysis were performed at initial molar ratios of Br2 to olefin of 1 to 2, so that products arose only from the cis olefin, the trans isomer being accumulated in the reaction medium. 

Similar results were obtained in methanol (ref. 30), where for the bis-(trifluoromethyl) derivative the ratio between the return of the trans bromonium ion to the trans olefin and its collapse to products 2 and 6 is 4.5 and is again very strongly reduced by the presence of LiC104 (Table 9). In this solvent, however, return was not observed for unsubstituted stilbene, either. It can be observed that both cis - and trans -stilbene gave methoxybromo adducts in an anti stereospecific way, suggesting a nucleophilic assistance by the solvent. 

The use of ester and formyl groups for this reaction is also possible. The reaction of methyl benzoates with olefins proceeds when the benzoates have electron-withdrawing substituents such as trifluoromethyl, cyano, and ester groups (Equation (8)).5,5a In the case of aldehydes, the reaction requires sterically hindered substituents such as tert-butyl and trimethylsilyl groups.6... 

The 0/7/fo-alkylation of aromatic ketones with olefins can also be achieved by using the rhodium bis-olefin complex [C5Me5Rh(C2H3SiMe3)2] 2, as shown in Equation (9).7 This reaction is applied to a series of olefins (allyltrimethyl-silane, 1-pentene, norbornene, 2,2 -dimethyl-3-butene, cyclopentene, and vinyl ethyl ether) and aromatic ketones (benzophenone, 4,4 -dimethoxybenzophenone, 3,3 -bis(trifluoromethyl)benzophenone, dibenzosuberone, acetophenone, />-chloroacetophenone, and />-(trifluoromethyl)acetophenone). 

The procedure illustrates a fairly general method for the preparation of -substituted perfiuoroolefins. The method has been applied to the synthesis of 2-cyclohexyl- (70%), 2-benzyl- (61%), and 2-(/>-fluorophenyl)perfluoropropenes (67%), and it is probably applicable to any a-trifluoromethyl ketone. Olefins containing a perfluoroalkyl group other than trifluoromethyl can be prepared by the same procedure by the substitution of lithium chlorodifluoroacetate for sodium chlorodifluoroacetate.7 Other routes to / -substituted perfiuoroolefins are not general or convenient. Routes to perfiuoroolefins generally yield the a-substi-tuted olefin rather than the /3-substituted olefin. 

Electrooxidative generation of trifluoromethyl radicals (CF3-) and their synthetic application have been developed since the early 1970s because trifluor-oaeetic acid (TFA) is readily available and one of the most economical starting materials for trifluoromethylation [61]. Heteroaromatics as well as olefins have been employed as substrates for the trifluoromethylation (Scheme 7.1) [62]. 

However, the selectivity for such trifluoromethylation has been rather low in many cases. For example, anodic trifluoromethylation of olefins provides a mixture of several types of products in general as shown in Scheme 7.2 and the control of the product-selectivity has been difficult [63]. 

Recently, Uneyama et al. have systematically investigated the anodic generation of CF3 radicals and their utilization (Scheme 7.3) [68-72], They have clarified that trifluoromethyl radicals can be generated almost quantitatively in the oxidation of TFA at 0 °C in an aq. MeOH/Pt system using an undivided cell [70]. They have also found that the trifluoromethylation of electron-deficient olefins can be controlled by the current density, reaction temperature, and the substituents of the olefins. Interestingly, anodic trifluoromethylation of fumar-... 

WITTIG OLEFINATION OF PERFLUOROALKYL CARBOXYLIC ESTERS SYNTHESIS OF 1,1,1-TRIFLUORO-2-ETHOXY-5-PHENYLPENT-2-ENE AND 1-PERFLUOROALKYL EPOXY ETHERS 1,1,1-TRIFLUORO-2-ETHOXY-2.3-EPOXY-5-PHENYLPENTANE (Oxirane, 2-ethoxy-3-(2-phenylethyl)-2-(trifluoromethyl)-, cis-(+)-)... 

Another example of type iii-a is the trifluoromethylation of double bonds by electrolysis of trifluoroacetic acid in the presence of olefins. Methyl vinyl ketone, vinyl acetate, diethyl fumarate, diethyl maleate, Ai-ethylmaleimide, and 2,5-dihydrothiophene-l,1-dioxide were examined as olefins. The products were bis-trifluoromethylated additive dimers (66) (type iii-a) and monomers (67) (type... 

A type iii-d reaction leads to the formation of (69). Trifluoromethyl radicals generated electrochemically from triflu-oroacetate can attack electron-deficient olefins leading to trifluoromethylated carbon radicals whose chemical and electrochemical follow-up reactions can be controlled by current density, reaction temperature, and substituents of the olefins. With fumaronitrile (86) at 50 °C the monotri-fluoromethylated compound (87) was obtained in 65% yield (Scheme 31) [110]. 

Trifluoromethyl-substituted olefins appear to also be problematic substrates for asymmetric hydrogenation as very long amounts of time and high pressures were required to achieve appreciable yields with ligand 10b (Scheme 9) [49]. Nevertheless, useful yields and excellent enantioselectivities were obtained for most examples. 

Phosphinodihydroxazole (PHOX) compounds, L2-4, act as P/N bidentate ligands showing excellent enantioselectivity in Ir-catalyzed hydrogenation of simple a,a-disubstituted and trisubstituted olefins (Figure 1.12). " The use of tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArp) as a counter anion achieves high catalytic efficiency due to avoidance of an inert Ir trimer... 

The transfer of a trifluoromethyl group of xanthate R—O—(C=S)—S—CF3 is a recent and powerful method for the trifluoromethylation of olefin.An important and interesting point of this method is that the reaction product is a xanthate itself, able to undergo further radical reactions and permitting cascade reactions, as exemplified in Figure 2.40. The starting xanthates R—O—(C=S)—S—CF3 are easily prepared from trifluoroacetic anhydride and sodium xanthate. 

Anesthesia is achieved rapidly and smoothly with sevoflurane, and recovery is more rapid than with isoflurane. However, sevoflurane is chemically unstable when exposed to carbon dioxide absorbents in anesthesia machines, degrading to an olefinic compound (fluoromethyl-2,2-difluoro-l-[trifluoromethyl]vinyl ether, also known as compound A) that is potentially nephrotoxic. In addition, sevoflurane is metabolized by the liver to release fluoride ions, raising concerns about potential renal damage. 

Trialkyl(trifluoromethyl)tin reacted with sodium iodide at 80 °C to form difluorocarbene in situ, which gave the difluorocyclopropane derivatives in the presence of olefins [108-110] (Scheme 39). 

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