Carbanions nitrile-derived

A variety of carbanionic species derived from carboxylic acids, esters, amides, and nitriles have been prepared and added to aldehydes and ketones. Usually, strong bases such as lithium diisopropylamide are used owing to the low level of... 

Carboxyl and nitrile groups are usually introduced in synthesis with commercial carboxylic acid derivatives, nitriles, or cyanide anion. Carbanions can be carboxylated with carbon dioxide (H.F. Ebel, 1970) or dialkyl carbonate (J. Schmidlin, 1957). 

A classical way to achieve regioselectivity in an (a -i- d -reaction is to start with a-carbanions of carboxylic acid derivatives and electrophilic ketones. Most successful are condensations with 1,3-dicarbonyl carbanions, e.g. with malonic acid derivatives, since they can be produced at low pH, where ketones do not enolize. Succinic acid derivatives can also be de-protonated and added to ketones (Stobbe condensation). In the first example given below a Dieckmann condensation on a nitrile follows a Stobbe condensation, and selectivity is dictated by the tricyclic educt neither the nitrile group nor the ketone is enolizable (W.S. Johnson, 1945, 1947). 

Inductive and resonance stabilization of carbanions derived by proton abstraction from alkyl substituents a to the ring nitrogen in pyrazines and quinoxalines confers a degree of stability on these species comparable with that observed with enolate anions. The resultant carbanions undergo typical condensation reactions with a variety of electrophilic reagents such as aldehydes, ketones, nitriles, diazonium salts, etc., which makes them of considerable preparative importance. 

Nucleophilic attack by carbanion occurs in the reaction of 2-nitrobenzamides 154 treated with sodium ethoxide (72JCS(P1)835). The reaction mixtures usually contain small amounts of nitrile 155 and carboxamide 156, the product of decarboxylation 158 being usually the principal product (Scheme 24). The corresponding bromo derivatives under the used conditions did not react. 

Treatment of the carbanion derived from 94 with nitriles was shown to give enaminesulfoxides 136, which can be converted to a-ketoesters or a-ketoacylamides185, besides the ester of JV-acetylamino acid 137. Using this reaction, the methyl ester of dl-JV-acetyl-5-hydroxytryprophane 138 was synthesized186. 

Treatment of a-lithionitriles with vinylic sulfones resulted in the formation of cyclized products, i.e., 3-oxothian-l, 1-dioxides 346 or cyclopropane derivatives 348. When a-lithiated aliphatic nitriles were used, carbanions 343, formed by the nucleophilic addition,... 

The catalytic conditions (aqueous concentrated sodium hydroxide and tetraalkylammonium catalyst) are very useful in generating dihalo-carbenes from the corresponding haloforms. Dichlorocarbene thus generated reacts with alkenes to give high yields of dichlorocyclopropane derivatives,16 even in cases where other methods have failed,17 and with some hydrocarbons to yield dicholromethyl derivatives.18 Similar conditions are suited for the formation and reactions of dibromocar-benc,19 bromofluoro- and chlorofluorocarbene,20 and chlorothiophenoxy carbene,21 as well as the Michael addition of trichloromethyl carbanion to unsaturated nitriles, esters, and sulfones.22... 

Carbamate herbicides, 13 320 Carbamates, 13 108 amine, 16 359 Carbamic acid nitrile, 3 158 Carbamide derivatives, as cellulose solvents, 11 272 Carbamodiimide, 8 158 Carbamoylated gelatin, 12 444 Carbamoyl-methylphosphoryl family, extractants of, 10 789 Carbamyl chlorides, 12 180 Carbanion coordination, 13 656—657 Carbanions, 21 101... 

Decarboxylation of 1,3-dimethylorotic acid in the presence of benzyl bromide yields 6-benzyl-1,3-dimethyluracil and presumably involves a C(6) centered nucleophilic intermediate which could nonetheless have either a carbene or ylide structure. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry has been used to explore the gas-phase reactions of methyl nitrate with anions from active methylene compounds anions of aliphatic ketones and nitriles react by the 5n2 mechanism and Fco reactions yielding N02 ions are also observed nitronate ions are formed on reaction with the carbanions derived from toluenes and methylpyridines. 

This methodology is also an important and potentially valuable method for C—N bond formation using the amination of carbon nucleophiles with electrophilic nitrogen transfer reagents (Scheme 1) Amination of ordinary carbanions and a-carbanion derived from carbonyl compounds and nitriles provides an important method for the synthesis of amines and a-amino carbonyl compounds and nitriles", respectively. For this purpose, a number of electrophilic amination reagents, which are synthetic equivalents of the R2N+ synthon, have been developed and the synthetic potential of electrophilic amination of carbon nucleophiles has been studied in detail . ... 

Scheme 2.4. Addition Reactions of Carbanions Derived from Esters, Carboxylic Acids, Amides, and Nitriles... 

A condensation reaction leads to a product with a new C—C bond. Most often the new bond results from a nucleophilic addition of a reasonably stable carbanion-enolate to the C=0 group (acceptor) of an aldehyde less frequently the 0=0 group belongs to a ketone or acid derivative. Another acceptor is the C=N group of a nitrile. 

Many other uses of a-sulfinyl carbanions are found in the literature, and in the recent past the trend has been to take advantage of the chirality of the sulfoxide group in asymmetric synthesis. Various ways of preparation of enantiopure sulfoxides have been devised (see Section 2.6.2) the carbanions derived from these compounds were added to carbonyl compounds, nitriles, imines or Michael acceptors to yield, ultimately, with high e.e. values, optically active alcohols, amines, ethers, epoxides, lactones, after elimination at an appropriate stage of the sulfoxide group. Such an elimination could be achieved by pyrolysis, Raney nickel or nickel boride desulfurization, reduction, or displacement of the C-S bond, as in the lactone synthesis reported by Casey [388]. 

The addition of unstabilized a-nitrile carbanions to a,3-unsaturated carbonyl acceptors affords predominantly 1,2-addition products, 56 while lithiated acetonitrile derivatives having a-alkoxy, a-aromatic, a-dialkylamino, a-phenylselenyl, a-phenylthio or a-trimethylsilyl substituents afford 1,4-adducts. However, some of these are acyl anion equivalents (Section 1.2.2.3.2) so this discussion is limited to a-stabi-lized nitriles in which the nitrile function is retained after removal of the activating group. Notable examples are trimethylsilylacetonitrile (208),157 phenylthioacetonitriles (209),158a b phenylselenylacetoni-... 

The reaction of aryl and hetaryl halides with the nitrile-stabilized carbanions (RC -CN) leads to derivatives of the type ArCH(R)CN. Sometimes, however, dimeric products of the type ArCH(R)CH(R)Ar are formed (Moon et al. 1983). As observed, 1-naphthyl, 2-pyridyl, and 2-quinolyl halides give the nitrile-substituted products, while phenyl halides, as a rule, form dimers. The reason consists of the manner of a surplus electron localization in the anion radical that arises upon replacing halogen with the nitrile-containing carban-ion. If the resultant anion radical contains an unpaired electron within LUMO covering mainly the aromatic ring, such an anion radical is stable, with no inclination to split up. It is oxidized by the initial substrate and gives the final product in the neutral form, Scheme 1-7 ... 

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