Trifluoromethyl-cyclopropane

The cyclopropane cyclizations by elimination of triflinic acid (CF3S02H) are readily effected by basic treatment of triflones (trifluoromethyl alkyl sulfones) with activated /-protons (equations 46 and 47)39. The cyclopropane diesters 45 are formed on treatment of 44 with potassium hydride in DMSO or sodium methoxide in methanol (equation 48). In contrast, the monoester 46 failed to give the desired cyclopropane40. Addition of carbanions derived from /f, y-unsaturated phenyl sulfones to a, /i-unsaturated carboxylic esters and subsequent elimination of benzenesulfinate ion give cyclopropanes possessing the unsaturated side chain and the ester function in trans positions (equation 49)41. 

More recently, Carreira reported a [Fe(TPP)Cl]-catalyzed diastereoselective synthesis of trifluoromethyl-substituted cyclopropane in aqueous media [56]. The carbene precursor trifluoromethyl diazomethane is difficult to be handled, generated in situ from trifluoroethyl amine hydrochloride, and reacts with styrene in the presence of [Fe(TPP)Cl] to give the corresponding cyclopropanes in high yields and with excellent diastereoselectivities (Scheme 12). 

A trifluoromethyl group attached to a cyclohexane ring is unremarkable with respect to its chemical shift, absorbing at -75 ppm, with a 3/fh = 8Hz (Scheme 5.2). There are no data available for trifluorometh-ylcyclopentane or cyclobutane. The chemical shift for trifluoromethyl-cyclopropane reflects additional shielding, such CF3 groups appearing the farthest upheld of any CF3-substituted hydrocarbon. 

Ring closure is a common feature of the reaction of sulfur tetrafluoride with cyclopropane-, cyclobutane- and cyclopentanepolycarboxylic acids. This tendency seems to be enhanced by steric crowding. Thus, m,tricarboxylic acid gives a 1 1 mixture of cyclic ether 13 and cis,trims-], 2,3-tris(trifluoromethyl)cyclopropane, whereas cyclopropane-... 

In order to sec the influence that a trifluoromethyl substituent has on cyclopropane reactivity, l-(trifluoromethyl)-2-vinylcyclopropane (18) was prepared and its thermal reactions studied.13 Both the cisitrans isomerization and the vinylcyclopropane rearrangement were slower than those of any 2-substituted vinylcyclopropane previously reported. When m-18 is heated at 275 C, a clean and reversible cisitrans isomerization takes place (Kequi, = 5.33). At 332-364 C, 18 undergoes normal vinylcyclopropane rearrangement to 4- and 3-(tri-fluoromethyl)cyclopentenc (19) and (20). respectively. 

Substituted fluorocarbenes, for example, arylfluorocarbenes 1, (alkoxycarbonyl)fluorocar-benes 2. fluoro(trichlorovinyl)carbene (3). fluoro(trifluoromethyl)carbenc (4). and (difluoromethyl)fluorocarbene (5), have been reported. Their addition to alkenes to give fluo-rinated cyclopropanes has been studied (see Table 2). 

The easiest reactions are those in which the nucleophile is the gold-activated species. Examples of this are Au(I)-catalyzed carbene and nitrene transfers (equations 142 and 143) that convert olefins into cyclopropanes or aziridines, respectively. In the carbene transfer, ethyl diazoacetate is the source of carbene and the active NHC-gold cationic catalyst is generated by chloride abstraction with sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate NaBAT4. The cyclopropanation is competitive with other carbene insertions with active C H or N H bonds present in the substrate. For the aziridinations of olefins, nitrene formation is accomplished by the oxidation of sulfonamides with PhI(OAc)2 and the catalyst of choice is a gold-(I) triflate with a terpyridine ligand. 

Fluorination of gew-dichlorocyclopropanecarboxylic acids leads to mixtures with 1,1-di-fluoroalkenes as major products and (trifluoromethyl)cyclopropanes as minor products.134... 

The monosubstituted (trifluoromethyl)carbene has only been generated by irradiation of 2,2,2-trifluorodiazocthane, which is prepared by nitrosation of 2,2,2-trifluoroethylamine.1,3 175 The course of reactions with alkenes is dependent on concentration and pressure conditions. Thus, insertion products and pyrazolines may be obtained in competition with [2+1] cycloaddition giving the cyclopropane system. Yields of the latter are often moderate and, depending on singlet or triplet carbene formation, the reaction is not always stereoselective (Table 14). 

Trifluoromethyl groups bonded to cyclopropane rings have received a limited amount of attention, mainly on account of synthetic problems associated with the substituent. The prismane 218 was synthesized by two groups and a singlet at 5 12.7 (with respect to external CF3CO2H in n-C5Fi2) was observed. A three band system of equal intensity at 20.3, 17.55 and 13.9 ppm was noted by Barlow and coworkers for 219. ... 

The kinetic acidity of trifluoromethyl cyclopropane (304) and of the corresponding isopropyl compound 305 have been determined by de Boer and coworkers As expected for the inductively operating CF3 group the cyclopropyl compound 304 exchanges with deuterium 5x10 — 5x10 times faster than 305. 

Photochemical k 280-300 nm) or thermal (>150 °C) decomposition of trifluoromethyl-sub-stituted diazo compounds 1 or diazirines 2 in the presence of excess alkene (acyclic or cyclic) yielded trifluoromethylcyclopropanes 3 and 4 in low to moderate yield (for examples see Houben-Weyl, Vol. E19b, p 1026). When the building block has two different substituents, the cyclopropane diastereomer resulting from the smaller steric interactions between the reactants is formed preferentially. 

Typically, C-C double bonds bearing one to four alkyl substituents were cyclopropanated. Methoxy(trifluoromethyl)carbene, generated by photochemical decomposition of 3-methoxy-3-trifluoromethyldiazirine, cyclopropanated both electron-rich (2-methylpropene, 2-methyl-but-1-ene, 2-methyl-but-2-ene) and electron-deficient C-C double bonds (acrylonitrile, ethyl acrylate) however, very low reactivity towards 2,3-dimethylbut-2-ene was observed for steric reasons (see Section 1.2.1.6.). °... 

The stereochemistry of these cyclopropanation reactions mainly depends on the carbene transferred, but it also depends on the alkene. Complete retention of the alkene configuration was observed when chloro(trifluoromethyl)carbene was transferred. 

The chloro(trifluoromethyl)carbene thus generated adds stereospecifically to (Z)-but-2-ene. The high temperature necessary for the decomposition of the mercurial substrate influences the formation of the cyclopropanes, the yields of which are sometimes low. 

In the case of cyclohexene, cyclopropanation to give 29 was accompanied by the insertion of the carbene into the allylic C-H bond giving 30. Cyclooctene forms both chloro- and bromo(trifluoromethyl)carbene addition products 31 and 32. Both reactions were rather slow. ... 

Electrochemical oxidation of stereospecifically deuterated titanacyclobutanes 17 or reaction with tetrakis(trifluoromethyl)cyclopentadienone (TTFC), 2,3-dichloro-5,6-dicyano-l,4-ben-zoquinone (DDQ) or ferricinium ion leads to stereospecific formation of cyclopropanes with a high degree of retention of configuration. ... 

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