A Fluorocarbenes

IS the most popular, one-step method for m ag fluorinated cyclopropanes and cyclopropenes a-Fluorocarbenes are particularly well behaved, because they all have singlet ground states [/, 2] and therefore usually add stereospecifically to alkenes and do not insert into C-H bonds competitively with addition Moreover, quantitative competition studies of carbene additions to alkenes near room temperature show that a-fluorocarbenes are more selective than other a-halocarbenes, with difluorocarbene being the most selective electrophihc carbene known [3, 4] The relative selectivities, however, can be quite temperature dependent [5, d] The numerous preparations and cycloaddmons of fluorocarbenes have been reviewed thoroughly [7, 8 9,10 ... 

The azomethine ylide represents one of the most reactive and versatile classes of 1,3-dipoles and is trapped readily by a range of dipolarophiles, forming substituted pyrroles or pyrrolidines (Coldham and Hufton 2005). Synthesis of aziridines by reaction of a fluorocarbene with imines under ultrasonic irradiation was described previously (Konev et al. 2005). This reaction proceeds by the formation of an azomethine ylide (9), which can be trapped with dimethyl maleate (13) to produce pyrrolidines (14) or pyrrole rings (15) in moderate yields (Scheme 8.5). 

Konev, A. S., Novikov, M. S. and Khlebnikov, A. F. 2005. The first example of the generation of azomethine ylides from a fluorocarbene 1,3-Cyclization and 1,3-dipolar cycloaddition. Tetrahedron Lett. 46 8337-8340. 

ChLorofluorocarbene generated by the thermal decomposition of dichlorofluoro-methylphenylmercury reacts with 2,3-dimethylindole to give 3-fluoro-2,4-di-methylquinoline, 3-chloro-2,4-dimethylqumoline and 3-(chlorofluoromethyl)-2,3-dimethylindole [f] (equation 1). Similar results are obtained when the chloro-fluorocarbene is generated from dichlorofluoromethane by base-catalyzed de-hydrohalogenation using a phase-transfer catalyst in an aqueous-organic solvent system [21 (equation 1). 

Hexafluoropropylene oxide (HFPO), which decomposes reversibly to di-fluorocarbene and trifluoroacetyl fluonde with a half-life of about 6 h at 165 °C [30], is a versatile reagent. Its pyrolysis with olefins is normally carried out at 180-2(X) °C, and yields are usually good with either electron-nch or electron-poor olefins [31, 32, 33, 34, 35, 36, 37] (Table 2). The high reaction temperatures allow the eyclopropanation of very electron poor double bonds [58] (equation 10) but can result in rearranged products [39, 40, 41] (equations 11-13)... 

In the cyclobutylfluoro system, the excited diazirine, 21-F, is considerably less involved. A parallel analysis indicates that only about 12% of 22-F and 23-F arise from excited diazirine, while 88% of those products descend from carbene 17-F.28 The increased carbene involvement in the photolysis of 21-F presumably reflects the greater stability of fluorocarbene 17-F over its chloro analogue 17-C1 and, consequently, a more favorable partition (ki/k3) of excited diazirine 21-F to the carbene. 

All fluorocarbenes are ground state singlets. For laboratory use there are some precursors which thermally generate difluorocarbene.42 Its identification is usually made by a subsequent chemical insertion reaction. A few industrially important processes proceed via difluorocarbene. The thermal pyrolysis of chlorodifluoromethane (CHF2C1) for the production of tetrafluoroethene and hexafluoropropene gives the intermediate CF2 which dimerizes to the alkene. 

Attempted insertions of fluorocarbenes into Sn—Mn and Sn—Fe bonds were unsuccessful thus, the thermal reaction of (CO)sMnSnMe3 with Me3SnCF3 (a good source of carbene CF2) led instead to a disproportionation reaction involving formation of (CO)5MnSnMe2(CF3) and SnMe4344. 

In the fluoromethyl radical, FCH2, the C—F bond [133.4(5) pm] is shorter than in all monofluorinated methane derivatives and the molecule is almost flat with a nearly sp2-hybridized carbon. The barrier to inversion is very low. The structures of fluorocarbene FCH and difluorocarbene (see Table 6) in the lowest singlet state were derived from UV spectra. These diradicals possess very short C—F bonds ca 130 pm) and are strongly bent with Z FCH = 104.1(13)° and Z FCF = 104.94°. 

Thermolysis of both F3CSiH3 and F2HCSiH3 in the presence of efficient carbene trapping agents have shown that they decompose predominantly by a-fluorine shift to give fluorosilane and the fluorocarbenes CF2 and CHF, respectively [24]. Secondary reactions at elevated temperature in the absence of any... 

The stereochemistry of reactions between carbenes and alkenes is determined by the states of the carbenes (when generated), whereby singlet carbenes react in a stereospecific one-step concerted process whilst triplet carbenes lead to a mixture of products via a diradical intermediate (Figure 6.58). Consequently, since fluorocarbenes are singlets in the ground state (Table 6.2), cyclopropanation of alkenes is often stereospecific [91] (Figure 6.59) (for more examples, see Sections A and B). 

The selectivity of carbenes has been qualitatively estimated by a series of competition reactions between various carbenes and mixtures of different alkenes it is found that electrophilic carbenes react preferentially with the most electron-rich alkene present [87, 92]. Fluorocarbenes, being less reactive, give rise to fewer products from C—H insertion reactions than CCI2 [91] (Figure 6.60). However, selectivity may be temperature-dependent [93, 94]. 

The photolysis and pyrolysis of difluorodiazirine has been shown to involve difluoromethylene and stereospecific addition to 2-butene indicates that it is probably in a singlet state. In argon or nitrogen matrices, Cp2 has been detected by spectroscopic measurements . Products arising from the thermolysis or photolysis of fluoromethoxydiazirine, cyanofluorodiazirine, difluoroaminodiazirine and chlorofluorodiazirine have been reported the main feature of these reactions is that the intermediate carbene in all cases can be trapped by olefin reagents, whereas fluorocarbenes from other sources are quite unreactive. 

Under acidic conditions, a-fluoro-a,P-unsaturated aldehydes form the thermodynamically stable Z-isomer. For the preparation of (Z)-aldehyde 19, acid hydrolysis of pyrane derivative 18, whose olefin-configuration corresponds to the E configuration, was affected due to facile isomerization under the reaction conditions. Pyrane 18 was obtained by chloro-fluorocarbene addition to dihydrofuran under phase-transfer conditions (see Scheme 10.5) [13]. (Z)-Aldehyde 19 was converted to Ph- /[(Z)-CF=CH]-Gly (20) using the same reactions for the preparation of the (ZTbisomer as described above (see Scheme 10.2). 

In the photolysis of fluorodihalomethanes, fluorodiiodomethane is usually used the yields of fluorocyclopropanes are low to poor. A free fluorocarbene is postulated as the intermediate in this reaction. 

Stereospecific cycloaddition of fluorocarbene to (Z)- and ( )-4-methylpent-2-ene supports the carbene rather than the radical mechanism for this step. An isomer ratio (cisjtrans) close to unity suggests that photolysis of fluorodihalomethanes generates a free carbene. Photolysis of fluorodibromomethane in cyclohexene gave 7-fluorobicyclo[4.1.0]heptane in 9% yield. ... 

The chiral and conformationally rigid Af-vinylcarbamate, (4/ ,55)-4,5-diphenyI-3-vinyloxa-zolidin-2-one, adds fluorocarbene, generated from fluorodiiodomethane and diethylzinc, in a highly diastereofacial selective manner to give (45,55)-3-(2-fluorocyclopropyl)-4,5-diphenyloxazolidin-2-one (7) as a mixture of all four possible diastereomers. ... 

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