Carbenes, fluorinated

Two other fluorine-containing diazirines give similar results. Cyanofluorodiazirine (223) and fluoromethoxydiazirine (224) release nitrogen at 100 °C the carbenes formed can be trapped by tetrafluoroethylene to give cyclopropanes (65JHC371). Without a carbene trap alkenes are obtained. 

The reactivities of the substrate and the nucleophilic reagent change vyhen fluorine atoms are introduced into their structures This perturbation becomes more impor tant when the number of atoms of this element increases A striking example is the reactivity of alkyl halides S l and mechanisms operate when few fluorine atoms are incorporated in the aliphatic chain, but perfluoroalkyl halides are usually resistant to these classical processes However, formal substitution at carbon can arise from other mecharasms For example nucleophilic attack at chlorine, bromine, or iodine (halogenophilic reaction, occurring either by a direct electron-pair transfer or by two successive one-electron transfers) gives carbanions These intermediates can then decompose to carbenes or olefins, which react further (see equations 15 and 47) Single-electron transfer (SET) from the nucleophile to the halide can produce intermediate radicals that react by an SrnI process (see equation 57) When these chain mechanisms can occur, they allow reactions that were previously unknown Perfluoroalkylation, which used to be very rare, can now be accomplished by new methods (see for example equations 48-56, 65-70, 79, 107-108, 110, 113-135, 138-141, and 145-146)... 

Various carbene-transfer reactions can be used with both electron-rich and electron-poor alkynes to make fluorinated cyclopropenes [9. 13, 79, 80, 81, 82] (Table 4). Haloacetylenes are too thermally unstable for most cycloaddition conditions, and simple fluorinated cyclopropenes are made by other methods [32, 45, 83, 84] (equations 30-32). 

Various highly fluorinated alkyltrifluorosilanes can be pyrolyzed at 140-200 °C with the loss of silicon tetrafluoride without affecting the carbon chain The resulting carbenes react with olefins m situ [103, 104] (equations 70-72)... 

A novel route to 2-fluoropyridines involved the base-induced decomposition of substituted N-fluoropyridinium salts. Abstraction of the 2-H produces a singlet carbene (11) that removes F from a counterion. This is in contrast to the reaction with C nucleophiles, which are fluorinated, and is attributed to the high stability of C—F compared to O—F and N—F (89JOC1726). 

For the most electronegative ligand, fluorine, we expect a relativistic destabilization in the Au—F bond, which was indeed determined to be —0.36eV at the coupled cluster level [182,183], Nevertheless, AuF has a sufficiently high dissociation energy of about 3.17 eV and has been identified recently in the gas phase [184]. In solution or in the solid state it would disproportionate to metallic Au and compounds of Au (AuF3 for the solid). However, a carbene-stabilized Au(I) fluoride was synthesized only very recently (see discussion in the next section) [185]. 

Figure 6.26. Carbene reaction catalysed by rhodium(II) complexes containing fluorinated...

Halogen substitution is expected to increase the electrophilicity of the carbenes, and in particular lh with four fluorine substituents is expected to be highly electrophilic and of unusual reactivity. All the carbenes le-g could be matrix-isolated by irradiation of their corresponding quinone diazides 2 in argon at 8-10 K.24 68,62 Again, the thermal reaction in (Vdoped matrices results in the formation of quinone oxides 7, which show the expected photochemical rearrangement to the spiro dioxiranes 8 and finally lactones 9. 

This catalytic tandem carbene addition-bicyclization of enynes has been very recently applied to the synthesis of fluorinated bicyclo[ .0.l]-amino esters.176... 

The DMS method has not been employed yet for the generation of 117 and 123, since the dibromocarbene adducts of norbomadiene and norbornene rearrange under the usual conditions for the preparation [89]. However, they could be synthesized at -60 °C by taking advantage of tetrabromomethane and methyllithium as a source of the carbene [90] and could prove stable enough to serve as precursors of 117 and 123. On the other hand, the adducts of bromofluorocarbene to norborna-diene and norbornene having the fluorine atom in a cis-orientation should be isol-able at room temperature and hence be usable as stable precursors of 117 and 123. These variations ofthe DMS method were published on the occasion ofthe preparation of cycloadducts of l-oxa-2,3-cyclohexadiene (351) (Section 6.3.6) [35, 91], 1,2,4-cyclohexatriene (162) and 3d2-lJ-f-naphthalene (221) (Section 6.3.4) [35, 92],... 

The stabilization of a carbanion brought by a- or )S-fluorine atoms is thermodynamic. Indeed, because of the great reactivity of carbanions toward elimination of a fluoride ion, they may have short lifetimes a-fluorinated carbanions easily undergo a-elimination processes to carbenes, while )S-fluorinated carbanions undergo jS-elimination reactions. 

Fluoroalkyl Glycosides (RFn-(CH2)2-n-0-sugar) and Perfluor-oalkylidene Acetals Derived from Sugars The very low nucleophilicity of fluoroalcohols makes it difficult to substitute of a hydroxyl (anomeric or not). ° This is the reason why this type of ether is not very common. Such ethers have only been isolated in very small quantities in solvolysis reactions, or in carben insertions, performed in fluorous alcohols.Preparation of these ethers has been solved by means of the Mitsunobu reaction. This reaction is known to be dependent on the pA a of the acceptor of the glycosyl the acidity of fluorous alcohols allows a much easier deprotonation than with non fluorinated alcohols." ... 

Fluorine substitution has greatly diminished the (negative) electrostatic potential for the internal double bond, but has had little effect on the potential for the external double bond. The change in selectivity (toward favoring addition onto the external double bond) is a direct consequence given that carbene addition is electrophilic addition. 

Benzene derivatives such as m-methylanisole (40) can be converted to distonic carbene ions. Reaction of 40 with O occurs with loss of H2, generating the conventional carbene anion 41 this anion reacts with molecular fluorine by dissociative ET, followed by nucleophilic attack of F on the methyl group, forming 42. In contrast to phenyhnethylene, 42 has a singlet ground state however, upon protonation it gives rise to the triplet state of m-hydroxyphenyl-methylene. This interesting reaction can be viewed as a spin-forbidden proton-transfer reaction. 

Even the F for Cl change transmuting CeHsCCl into CeHsCF is accompanied by a diminution in reactivity CeHsCF reacts about one-half as rapidly as CeHsCCl with the alkenes of Table 7.5. This lowering of reactivity can be attributed to greater stabilization of CeHsCX when X=F, as opposed to X=C1. Fluorine is a better resonance electron donor to the vacant carbene 2p orbital than chlorine, and this factor (rather than the greater electronegativity of fluorine) appears to be dominant. ... 

Further fluorinated synthons 20 (equation 17)92 and 21 lead to Reformatsky intermediates which are synthetic equivalents of a formal 4,4-difluoroacetoacetate dianion and of a carbalkoxy trifluoromethyl carbene, respectively. The latter has been exploited in a synthesis of E-22 and Z-22, both inhibitors of GABA aminotransferase (equation 18)93. 

Carboxamidation of heteroaromatic compounds, promoted by fluorine, provides a convenient alternative to the well-known Chichibabin amination reaction (Fig. 86) [228]. The mechanism of this reaction was suggested to proceed via a carbene intermediate (Fig 87). 

Many of these reactions also involve carbene intermediates [32] but they are treated separately because their synthetic equivalence is different. The chemistry described in this section allows the disconnection of targets to carbon nucleophiles and one-carbon fluorinated electrophiles. 

For reviews of flourinaled carbenes, see Seyferth in Moss Jones Carbenes, vol. 2 Wiley New York, 1975. pp. 101-158 Sheppard Sharis Organic Fluorine Chemistry W. A. Benjamin New York, 1969, pp. 237-270. Dolbier Burkholder Tetrahedron Lett. 1988, 29, 6749. 

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