Reaction mechanisms carbanions

Carbanions are very useful intermediates in the formation of carbon-carbon bonds. This is true both for unstabilized structures found in organometallic reagents and stabilized structures such as enolates. Carbanions can participate as nucleophiles both in addition and in substitution reactions. At this point, we will discuss aspects of the reactions of carbanions as nucleophiles in reactions that proceed by the 8 2 mechanism. Other synthetic aj lications of carbanions will be discussed more completely in Part B. 

In the case of carbanion and radical intermediates the solvent is less important but the products are partially determined by the resistance of the medium to proton or hydrogen atom abstraction respectively. The increased stability of these intermediates compared with carbonium ions allows the reaction mechanism to be more readily modified by the addition of trapping agents. For example, carbanions are trapped in high yields by the presence of carbon dioxide in the electrolysis medium (Wawzonek and Wearring, 1959 Wawzonek et al., 1955). 

Although the reaction mechanism of this type of reactions is not fully elucidated, it is easily anticipated that no intramolecular special stabilization effect for the carbanion generated from decarboxylation is expected, different from the case of malonic acid-type compounds. Moreover, cinnamic acid derivatives that have both the electron-donating and withdrawing substituents have been reported to undergo this reaction. This fact suggests that the enzyme itself stabilizes the transition state without the aid of mesomeric and inductive effects of the other part of the substrate molecule itself. If such unknown mechanism also works for other... 

In terms of the carbanion equivalent, the enolase superfamily has a strong relation with decarboxylation reaction. This family is characteristic in its promiscuity. If one is reminded of the phrase lock and key theory for the relation between the substrate and the enzyme, the word promiscuity of the enzyme may be unbelievable. However, in addition to natural promiscuity, we can change the enzyme to be promiscuous by introducing mutation, especially in the case of the enolase superfamily. This will be one of the challenging problems in future. For that purpose, biotechnology and informatics skill will be essential tool in addition to precise analysis of the reaction mechanism. 

The fundamental aspects of the structure and stability of carbanions were discussed in Chapter 6 of Part A. In the present chapter we relate the properties and reactivity of carbanions stabilized by carbonyl and other EWG substituents to their application as nucleophiles in synthesis. As discussed in Section 6.3 of Part A, there is a fundamental relationship between the stabilizing functional group and the acidity of the C-H groups, as illustrated by the pK data summarized in Table 6.7 in Part A. These pK data provide a basis for assessing the stability and reactivity of carbanions. The acidity of the reactant determines which bases can be used for generation of the anion. Another crucial factor is the distinction between kinetic or thermodynamic control of enolate formation by deprotonation (Part A, Section 6.3), which determines the enolate composition. Fundamental mechanisms of Sw2 alkylation reactions of carbanions are discussed in Section 6.5 of Part A. A review of this material may prove helpful. 

The photodecarboxylation of nitrophenyl acetate in aqueous media was also investigated recently89 -92, especially with respect to the kinetic and spectral properties of the photogenerated p-nitrobenzyl carbanion its triplet state (Xmax ca 290 nm) was identified to have a lifetime of 90 nanoseconds at pH > 5.0. The proposed reaction mechanism following 266-nm laser excitation of p-nitrophenyl acetate is summarized in Scheme 792. 

Biocatalytk decarboxylation is a imique reaction, in the sense that it can be considered to be a protonation reaction to a carbanion equivalent intermediate in aqueous medimn. Thus, if optically active compoimds can be prepared via this type of reaction, it would be a very characteristic biotransformation, as compared to ordinary organic reactions. An enzyme isolated from a specific strain of Alcaligenes bronchisepticus catalyzes the asymmetric decarboxylation of a-aryl-a-methyhnalonic acid to give optically active a-arylpropionic acids. The effect of additives revealed that this enzyme requires no biotin, no co-enzyme A, and no ATP, as ordinary decarboxylases and transcarboxylases do. Studies on inhibitors of this enzyme and spectroscopic analysis made it clear that the Cys residue plays an essential role in the present reaction. The imique reaction mechanism based on these results and kinetic data in its support are presented. 

The reactions of sodium dimethyl and diisopropyl phosphite with 4-nitrobenzyl chloride, 9-chlorofluorene, and diphenylchloromethane provided information that supported the proposed reaction mechanism. The RaPO anion acts towards an arylmethyl chloride as a base and abstracts a proton to form a carbanion, which can then participate in single-electron transfer processes to produce carbon-centred radicals. ... 

This chapter on electrophilic amination using O-substituted hydroxylamines 1-5 and oximes 7 is focused on the various methods that have been reported for the amination of carbon nucleophiles. Synthetic aspects and applications of the methods for C—N bond formation are accompanied by a brief discussion of the reaction mechanisms. The preparation of O-substituted hydroxylamines and oximes has not been considered in detail. This review covers the literature up to August 2007 and is partly based on reviews on the electrophilic amination of carbanions and a-amination of carbonyl compounds. ... 

Carbanions play critical roles in a wide variety of reaction pathways. As stated in the Introduction, this chapter will not focus on the synthetic utility of carbanions, but will instead focus on their mechanistic significance. In this section, a sample of important reaction mechanisms that involve transient or relatively short-lived car-banion intermediates will be introduced. As you will see, the key element in these mechanisms is the ability to form a carbanion that is reasonably stable, and often the kinetics of the reactions are dominated by carbanion stability. The role of carbanion intermediates in elimination reactions will be presented in some detail as a way to illustrate some of the methods that have been developed to probe for carbanion intermediates in reaction mechanisms. Other processes including additions and rearrangement reactions will be presented in less detail, but the role of carbanion stability in these reactions will be outlined. 

As noted in Section 4.2.1, the gas phase has proven to be a useful medium for probing the physical properties of carbanions, specifically, their basicity. In addition, the gas phase allows chemists to study organic reaction mechanisms in the absence of solvation and ion-pairing effects. This environment provides valuable data on the intrinsic, or baseline, reactivity of these systems and gives useful clues as to the roles that solvent and counterions play in the mechanisms. Although a variety of carbanion reactions have been explored in the gas phase, two will be considered here (1) Sn2 substitutions and (2) nucleophilic acyl substitutions. Both of these reactions highlight some of the characteristic features of gas-phase carbanion chemistry. 

Scheme 2.2.3.2 Reaction mechanism of PDC and BFD. C2 of the cofactor ThDP is the real active site of both enzymes. The cofactor is regenerated during the reaction cycle. Decarboxylation of 2-keto acids and carboligation of aldehydes have a common reaction intermediate (enamine-carbanion = active aldehyde ).

To account for these results we can propose the following mechanism for the reaction of carbanions onto elemental sulfur ... 

The nature of the catalyst and certain experimental observations, such as product distribution [Eq. (5.61)], indicate a carbanionic reaction mechanism. A benzylic carbanion formed through proton abstraction by an organoalkali metal compound... 

The fate of the onium carbanion Q+R incorporated into the organic phase depends on the electrophilic reaction partner. The most studied area in the asymmetric phase-transfer catalysis is that of asymmetric alkylation of active methylene or methine compounds with alkyl halides, in an irreversible manner. The reaction mechanism illustrated above is exemplified by the asymmetric alkylation of glycine Schiff base (Scheme 1.5) [8]. 

The mechanistic borderline between E2 and ElcB mechanisms has been studied under various conditions.1,2 The mechanism of the elimination reaction of 2-(2-fluoroethyl)-1-methylpyridinium has been explored explored by Car-Parrinello molecular dynamics in aqueous solution.3 The results indicated that the reaction mechanism effectively evolves through the potential energy region of the carbanion the carbon-fluoride bond breaks only after the carbon-hydrogen bond. 

A convenient route to trivinylphosphine has been developed by thiol elimination from tris[2-(phenylthio)ethyl]phosphine oxide.56 The reaction mechanism involves a phosphoryl-stabilized carbanion, from which benzene thiolate anion is eliminated. 

Reutov, 0. A., and 7. P. Beletskaya (transl. by A. M A. Mincer) Reaction Mechanisms of Organometallic Compounds, Chap. 1 (The Chemistry of Carbanions). Amsterdam North-Holland Publishing Co. 1968. 

First steps to elucidate the reaction mechanism of PDC were achieved by the investigation of model reactions using ThDP or thiamine [36,37], Besides the identification of C2-ThDP as the catalytic center of the cofactor [36], the mechanism of the ThDP-catalyzed decarboxylation of a-keto acids as well as the formation of acyloins was explained by the formation of a common reaction intermediate, active acetaldehyde . This active species was first identified as HEThDP 7 (Scheme 3) [38,39]. Later studies revealed the a-carbanion/enamine 6 as the most likely candidate for the active acetaldehyde [40 47] (for a comprehensive review see [48]). The relevance of different functional groups in the ThDP-molecule for the enzymatic catalysis was elucidated by site-directed substitutions of the cofactor ThDP by chemical means (for a review see... 

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