Carbanionic nucleophile

The most useful reactions combine carbanion nucleophiles with activated aziridines. For example, the ring expansion which occurs on treatment of aziridines (219) with malonate salts typifies the heterocyclic synthesis possible. The conversion is quite general since many analogous transformations have been observed in which different carbanion stabilizing substituents were employed (73S546). 

A different kind of alkylation of nitro compounds uses carbanion nucleophiles that have a chlorine at the carbanionic carbon. The following process takes place ... 

Recently, the iron-promoted Barbier-type addition of alkyl halides to aromatic aldehydes has been reported (Equation (26)).326 According to the proposed mechanism, the initial step is the formation of an alkyl radical, which can be reduced to the corresponding carbanion. This carbanion nucleophile can react, while coordinated to the iron pentacarbonyl complex, with the corresponding aldehyde. This stoichiometric method is limited with respect to substrate scope and yield. The same authors have also developed the Reformatsky-type addition of cr-halosub-stituted carbonitriles to aldehydes and ketones in the presence of iron pentacarbonyl.3... 

Though this topic is treated here under a separate heading, alkylation of enolate anions is nothing other than enolate anions acting as carbanion nucleophiles in Sn2 reactions. We deferred this topic... 

An enolate anion behaves as a carbanion nucleophile, the carbonyl group stabilizing the anion by... 

The intramolecular addition of carbon nucleophiles to alkenes has received comparatively little attention relative to heterocyclization reactions. The first examples of Pd-catalyzed oxidative carbocyclization reactions were described by Backvall and coworkers [164-166]. Conjugaled dienes with appended al-lyl silane and stabilized carbanion nucleophiles undergo 1,4-carbochlorination (Eq. 36) and carboacetoxylation (Eq. 37), respectively. The former reaction employs BQ as the stoichiometric oxidant, whereas the latter uses O2. The authors do not describe efforts to use molecular oxygen in the reaction with allyl silanes however, BQ was cited as being imsuccessful in the reaction with stabihzed car-banions. Benzoquinone is known to activate Ti-allyl-Pd intermediates toward nucleophilic attack (see below. Sect. 4.4). In the absence of BQ, -hydride eUm-ination occurs to form diene 43 in competition with attack of acetate on the intermediate jr-allyl-Pd" species to form the 1,4-addition product 44. 

Nagamatsu and co-workers also reported the reaction of 30 with hydrazine to produce 31, a key intermediate in the synthesis of potential xanthine oxidase inhibitors 32 <99CC1461>. The regioselectivity of this hydrazine displacement thus paralleled that observed with carbanionic nucleophiles. 

The acidity of the ring proton of the thiamine ring is a consequence of the adjacent positive nitrogen and the known ability of sulfur to stabilize an adjacent carbanion. Nucleophilic attack of the anionic carbon of 10 on C2 of 2-oxopro-panoic acid is followed by decarboxylation ... 

Many carbanionic nucleophiles that would be considered too hard to react as Michael donors can be made into effective reagents for conjugate addition reactions by appending resonance or inductively stabilizing groups to soften their intrinsic Lewis basicity. Such stabilized anionic Michael donors include enolates, alkylthio-substituted carbanions, ylides and nitro-substituted carbanions. 

Having defined the types of commonly used carbon nucleophiles and carbon electrophiles, it would seem that if you react any of the carbon nucleophiles (electron donors) with any of the carbon electrophiles (electron acceptors), then a carbon-carbon bond should be formed. While this is theoretically true, it is unworkable from a practical point of view. If, for example, a carbanion nucleophile was reacted with a cationic electrophile, it is unlikely that the desired carbon-carbon bond formation would be detected, even after the smoke cleared. Or if a silyl enol ether nucleophile was reacted with an a, /f-unsaturated ester, no reaction could be observed to take place in any reasonable time frame. 

A second way to make organometallic compounds for use as carbanion nucleophiles is to use halogen-metal exchange. In this process an alkyl halide... 

Enolates and related carbanionic nucleophiles are routinely generated by removal of an acidic proton in a molecule with a base. Carbonyl groups acidify their a protons somewhat and make dieir removal by a base a common process. However, structural features other than carbonyl groups can also acidify protons bound to carbon and thus facilitate dieir removal by bases. For example, pK values for structurally acidified C-H protons include the ones given below. 

Photo-stimulated reactions of neopentyl iodide with several carbanionic nucleophiles have been studied in which inhibition experiments with the TEMPO radical trap suggest the reaction occurs via an SrnI mechanism.76 Comparison of 22 nucleophiles in then. Srn 1 reactions with iodobenzene by Fe(II)- and photo-induction has revealed that both are enhanced by high electron-donation ability of the nucleophile. The radical anion Phl is a key intermediate.77 The SET reactions of perfluoroalkyl iodides have been reviewed.78 Flash photolysis of H2O2 was used to generate HO and 0 radicals which were reacted with a, a. z-trifluorotolucnc (TFT) and 4-fluorotoluene (4FT) and the rate constants calculated.79 The diminished reactivity of TFT towards HO or O with respect to toluene or benzene was consistent with radical addition to the aromatic ring, whilst the reactivity of 4FT was of the same order as electron-deficient toluenes, which favour H abstraction from the aliphatic side-chain. 

The photolysis of aromatic species with tetranitromethane in perfluoro alcohol solvent has been studied, in which the radical cations were observed by EPR spectroscopy.284 Photo-stimulated reaction of 1- and 2-haloadamantanes and 1,2- and 1,3-dihaloadamantanes with various carbanionic nucleophiles afforded products rationalized through an SrnI mechanism.285 286 Photolysis of the cycloadduct formed between a functionalized derivative of C6o and diazomethane has been shown to afford a pah of ling-opened structures (125) and (126) via a proposed biradical intermediate (127) (Scheme 19). The UV-photolytic fragments of /-butyl iodide (T and /-Bu ) have been ionized by resonance-enhanced multiphoton ionization for TOF mass spectro-metric analysis.287 A two-dimensional position-sensitive detector provided angular distribution and translational energy data. 

Photostimulated, S r k 1 reactions of carbanion nucleophiles in DMSO have been used to advantage in C—C bond formation (Scheme 1).25-27 Thus, good yields of substitution products have been obtained from neopentyl iodide on reaction with enolates of acetophenone and anthrone, but not with the conjugate base of acetone or nitromethane (unless used in conjunction, whereby the former acts as an entrainment agent).25 1,3-Diiodoadamantane forms an intermediate 1-iodo mono substitution product on reaction with potassium enolates of acetophenone and pinacolone and with the anion of nitromethane subsequent fragmentation of the intermediate gives derivatives of 7-methylidenebicyclo[3.3.1]nonene. Reactions of 1,3-dibromo- and 1-bromo-3-chloro-adamantane are less effective.26... 

Photoassisted heteroaromatic nucleophilic substitution reactions of various carbanion nucleophiles with 2-bromopyridine, iodobenzene, bromobenzene, bromomesitylene, and 2-chloroquinoline in KNH2-liquid NH3 have also been compared.27... 

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