Carbanions cyano

A variety of ring syntheses have been devized which depend on carbanion addition to an activated double bond. The examples depicted in Scheme 74 illustrate the use of inter alia cyano and nitro groups which are subsequently eliminated. In appropriate instances the inclusion of additional eliminable groups ensures the formation of fully aromatized products. 

The formation of ethyl cyano(pentafluorophenyl)acetate illustrates the intermolecular nucleophilic displacement of fluoride ion from an aromatic ring by a stabilized carbanion. The reaction proceeds readily as a result of the activation imparted by the electron-withdrawing fluorine atoms. The selective hydrolysis of a cyano ester to a nitrile has been described. (Pentafluorophenyl)acetonitrile has also been prepared by cyanide displacement on (pentafluorophenyl)methyl halides. However, this direct displacement is always aecompanied by an undesirable side reaetion to yield 15-20% of 2,3-bis(pentafluoro-phenyl)propionitrile. 

The thenyl cyanides are of great importance for the preparation of thiophene derivatives. Because of the acidifying effects of both the thienyl and of the cyano groups, carbanions are easily obtained through the reaction with sodamide or sodium ethoxide, which can be alkylated with halides, carbethoxylated with ethyl carbonate, or acylated by Claisen condensation with ethyl... 

Base catalyzed condensation of 2-azidobenzaldehyde 796 with cyano-carbanions in piperidine or NaOEt in ethanol afforded tetrazoloquinolines... 

A cyanide anion as a nucleophile adds to an aldehyde molecule 1, leading to the anionic species 3. The acidity of the aldehydic proton is increased by the adjacent cyano group therefore the tautomeric carbanion species 4 can be formed and then add to another aldehyde molecule. In subsequent steps the product molecule becomes stabilized through loss of the cyanide ion, thus yielding the benzoin 2 ... 

The mechanism of these reactions is usually Sn2 with inversion taking place at a chiral RX, though there is strong evidence that an SET mechanism is involved in certain cases, ° especially where the nucleophile is an a-nitro carbanion and/or the substrate contains a nitro or cyano group. Tertiary alkyl groups can be introduced by an SnI mechanism if the ZCH2Z compound (not the enolate ion) is treated with a tertiary carbocation generated in situ from an alcohol or alkyl halide and BF3 or AlCla, or with a tertiary alkyl perchlorate. ... 

The mechanism of the cyanide- and thioazolium ion-catalyzed conjugate addition reactions is considered to be analogous to the Lapworth mechanism for the cyanide-catalyzed benzoin condensation. Thus the cyano-stabilized carbanion resulting from deprotonation of the cyanohydrin of the aldehyde is presumed to be the actual Michael donor. After conjugate addition to the activated olefin, cyanide is eliminated to form the product and regenerate the catalyst. 

In the course of the salt synthesis, it was found that a hydrocarbon [3-2], which was formed by an unfavourable cation-anion combination reaction, dissociates into the original carbocation and carbanion in a polar aprotic solvent (Okamoto et ai, 1985) (1). This was the first example of ionic dissociation of the carbon-carbon a bond in genuine hydrocarbons, although a few cases of heterolytic dissociation of carbon-carbon tr bonds had been reported by Arnett (Arnett et al., 1983 Troughton et al., 1984 Arnett and Molter, 1985) for compounds bearing cyano and nitro groups, e.g. [4-6] and [5-6] as in (2). 

The cyano-, carbomethoxy- and phenylsulfonyl-substituted cyclopropanes [54] (Cram and Ratajczak, 1968), [55] (Yankee and Cram, 1970a Yankee et al., 1973a) and [56] (Yankee and Cram, 1970b,c Howe etal., 1973 Yankee et al., 1973b) were epimerized or were solvolysed to give an open-chain methyl ether a carbocation-carbanion zwitterion was proposed as the intermediate. 

A carbanion can be a good leaving group in SNl-type solvolyses when the anion is highly stabilized by strong electron-withdrawing substituents. Mitsuhashi reported some examples of such reactions for substrates which eject an anion stabilized by cyano (and nitro) groups [81] (Mitsuhashi, 1986), [82] (Mitsuhashi and Hirota, 1990) and [83] (Hirota and Mitsuhashi,... 

In view of the observations of the ionic dissociation of nitro-cyano compounds, it is hardly surprising that even a hydrocarbon could dissociate ionically into a stable carbocation and carbanion, provided that the medium is polar enough to prevent the recombination reaction and to ensure equilibration. 

As shown in Fig. 3, the observed values of A/fhet(R-R ) in DMSO for the hydrocarbons [3-2] and [25-2] are 15kcalmol less than the values predicted from (28) and (29), respectively, while A/fi,et(R-R ) for the nitro-cyano compound [4-102] in acetonitrile (30) is close to the value predicted from (29). Therefore, this departure of the dissociative hydrocarbons from the predicted behaviour can be ascribed to steric congestion in the hydrocarbon, predominantly caused by the carbanion moiety [2 ]. 

A recent paper (199 3)195 is devoted largely to the behaviour of cyano carbanions. It is concluded that the stabilization of carbanions by CN does not actually involve considerable transfer of 7r charge from the carbanionic carbon to CN. This does not, however, appear to have any implications for the explanation of stabilization of carbanions by the nitro group in terms of delocalization. 

In the reaction of the phenylacetonitrile carbanion with thiocyanates, a major side reaction leads to the formation of the dialkyl disulphides, as a result of the base-catalysed decomposition of the thiocyanate. This side reaction is reported to be insignificant in the reactions of the other carbanions. Phenylacetonitrile reacts with 1,2-ethanyl bisthiocyanate to produce 2-cyano-2-phenyl-1,3-thiolanes [52] under conditions analogous to those used for the synthesis of the thioethers (Scheme 4.12). 

Although not a Michael acceptor, vinyl acetate reacts with a range of carbanions under phase-transfer catalytic conditions [61]. 1 1 Adducts are obtained from 1-cyano-l-phenylalkanes, but phenylacetonitrile produces a 2 1 adduct with loss of acetic acid (Scheme 6.28). The major product (40%) isolated from the reaction with diphenylmethyl cyanide is l,2-dicyano-l,l,2,2-tetraphenylethane. 

The previous sections have dealt primarily with reactions in which the new carbon-carbon bond is formed by an SN2 reaction between the nucleophilic carbanions and the alkylating reagent. Another important method for alkylation of carbon involves the addition of a nucleophilic carbon species to an electrophilic multiple bond. The electrophilic reaction partner is typically an a,/i-unsaturated ketone, aldehyde, or ester, but other electron-withdrawing substituents such as nitro, cyano, or sulfonyl also activate carbon-carbon double and triple bonds to nucleophilic attack. The reaction is called conjugate addition or the Michael reaction. Other kinds of nucleophiles such as amines, alkoxides, and sulfide anions also react similarly, but we will focus on the carbon-carbon bondforming reactions. 

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