Trifluoromethylation direct oxidative

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

The direct fluorination of sulphones has also been studied210 and this leads to oxidation. At room temperature dimethyl sulphone produced bis(trifluoromethyl)-sulphone and trifluoromethylsulphonyl fluoride in 34% and 15% yields respectively (equation 93). 

Another convenient entry to fused cyclobutene-1,2-diesters was via site selective modification of the norbomene rt-bond in Smith s fe-alkene 49, e.g. treatment with 3,6-di(2 -pyridyl)-s-tetrazine 51 followed by DDQ oxidation afforded the cyclobutene-derivative 53 <97AA119>, while direct coupling with 3,5-f> (trifluoromethyl)-l,3,4-oxadiazo]e 54 furnished the tas(cyclobutene-l,2-diester) 55 (Scheme 6) <97SL196>. 

Pteridine also adds ammonia at low temperature to form 4-amino-3,4-dihydropteridine (42) which is transformed in a slower reaction into 6,7-diamino-5,6,7,8-tetrahydropteridine (43) (Scheme 5). 2-Chloropteridine (36) shows the same behavior, whereas 2-chloro-4-phenylpteridine (37) and 2-methylthiopteridine (38) lead directly to the corresponding 6,7-diamino-5,6,7,8-tetrahydro derivatives (43) (Scheme 5). The 4-amino-3,4-dihydropteridines can easily be oxidized to the 4-aminopteridines <75RTC45>. Covalent hydrations with various 6,7-bis-trifluoromethyl-pteridine derivatives were studied showing that 6,7-bis-trifluoromethylpteridine (40) itself and the cor-... 

An alternative method whereby a fused-ring oxirene may be generated is the epoxidation of a cycloalkyne. Curci et al. have employed methyl(trifluoromethyl)dioxirane (TFD) toward that end, and obtained (215) and c -bicyclo[4.4.0]decan-2-one in ca. 7 1 ratio from cyclodecayne (213) <92TL7929>. These products obviously stem from stereoselective 1,5- and 1,6-transannular insertion pathways. The authors conclude that the products of cycloalkyne oxidations may arise directly from trapping of the oxirene intermediates by transannular hydrogen transfer, as shown in Scheme 46. 

Recently, 3,5-bis(trifluoromethyl)benzeneseleninic acid has been used in a tandem catalytic epoxidation." The concept of tandem catalysis has been applied to oxidation reactions by Backvall and co-workers for the direct dihydroxylation of olefins using a couple catalytic system and hydrogen peroxide as the terminal oxidant." In this context, the seleninic acid was used in combination with a trifluoromethyl oxaziridine catalyst (Scheme 17), using urea hydrogen peroxide as the terminal oxidant." This system showed... 

Epoxidation of allylic phosphonates is achieved wilh success at room temperature witli MeCOjH in Et O, CF3CO3H in CHCI3, MCPBA in ( HT I- or MOO5/HMPA complex in CH2CI2 to give the corresponding 2,3-epoxyalkylphosphonates as a mixture of diastereomers. s- Allylic phosphonates may also be converted into 2,3-epoxyphosphonates via the 1,1,1-trifluorodimethyl-dioxirane-mediated oxidation. Dimethyldioxirane (DMD) in acetone at room temperature or methyl(trifluoromethyl)dioxirane (TED) in CHjClj at low temperature can be used instead of MCPBA. Because the reaction is quantitative, evaporation of acetone and excess of DMD allow the direct isolation of the pure product. 2,i55... 

In comparison with the diazines, the inductive effects of the extra nitrogen(s) leads to an even greater susceptibility to nucleophilic attack and, as a result, all the parent systems and many derivatives react with water, in acidic or basic solution. Similarly, simple electrophilic substitutions do not occur some apparent electrophilic substitutions, such as the bromination of 1,3,5-triazine, probably take place via bromide nucleophilic addition to an N -Br triazinium salt. Attempted direct A-oxidation of simple tetrazines with the usual reagents generally results in ring cleavage, however it can be achieved satisfactorily with methyl(trifluoromethyl)dioxirane. ... 

The direct fluorination of sulphones has also been studied260 and this leads to oxidation. At room temperature dimethyl sulphone produced bis (trifluoromethyl)-sulphone and trifluoromethanesulphonyl fluoride in 34% and 15% yields, respectively. The latter was hydrolyzed in situ to the corresponding sulphonic acid (equation 49). Electrofluorination of either sulpholene or perfluorosulpholene leads to the formation of a sulphonic acid, after alkaline hydrolysis, as shown in equation 50261. 

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