Nitroalkanes deprotonation

In conclusion, we see that nitroalkane deprotonation may be understood in terms of a three-configuration picture. It is this third configuration which... 

Reactions (109) and (110) as well as nitroalkane deprotonation are all examples of central substitution so that for these reactions a does not measure the earliness or lateness of the transition state. End substitution, such as in the nucleophile or leaving group of SN2 reactions, in which the formal charge does vary between reactants and products generates -values which may be utilized as a relative measure of transition state charge this, provided that the reaction is composed of three configurations. Such applications were discussed in Section 3, p. 152. 

We can complement this type of selectivity with the opposite type. Are there any compounds that can enolize but that cannot function as electrophiles No carbonyl compound can fill this role, but in Chapter 21 we met some enolizable compounds that lacked carbonyl groups altogether. Most notable among these were the nitroalkanes. Deprotonation of nitroalkanes is not enolization nor is the product an enoiate ion, but the whole thing is so similar to enolization that it makes sense to consider them together. The anions, sometimes called nitronates, react well with aldehydes and ketones. 

The base for the nitroalkane deprotonation may vary potassium /cr/-but oxide2 22, potassium carbonate23-24, or alumina-supported potassium fluoride25 are all effective. 

Evans and coworkers have developed an enantioselective copper-catalyzed ni-troaldol reaction that does not require the use of amine base. A catalyst derived from ligand (158) and Cu(OAc)2 was developed to act as a weakly Lewis acidic metal center capable of electrophile activation. The acetate counterion was chosen owing to its moderate basicity in the hope of facilitating nitroalkane deprotonation. This catalyst system performs admirably in additions of (154) to a broad scope of aldehydes (157) leading to nitroaldol products (159) in good yields with excellent enantioselectivity (Scheme 17.32). 

Method A ct,ct-Donbly deprotonated nitroalkanes react with aldehydes to give intermediate nitronate alkoxides, which afford iyti-nitroalcohols as major products d8 7-47 3 by kmedc protonadon at -100 C in THF-HMPA. The carcinogenic hexamethylphosphorons triamide fHMPAi can be replaced by the ntea derivadve (T)MPU. ... 

The reaedvity of carbon is much enhanced by the double deprotonated intermediates of nitro compounds. Except for nitromuhane, other nitroalkanes are alkylated to give the C-alkylated products in 50-60% yield by this procedure fsee Eq. 5.4. ... 

Another method for improving the reactivity of nitro compounds is provided by the double deprotonation of nitroalkanes. In this case, the reaction with ketones affords P-nitro alcohols in 40-60% yield (Eq. 3.19).30... 

Silylation of Products of Conjugated Addition of Nucleophiles to a-Nitroolefins Nitroalkane anions can be generated not only by deprotonation of nitroalkanes (various modifications of these process were considered above) but also by the conjugated addition of nucleophiles 56 to a-nitroalkenes (42) (Scheme 3.56, Table 3.2). 

As we have seen in Chapter 2 (Scheme 2.3, equation 3), the doubly deprotonated nitroalkanes are nitroalkenes with reactivity inversion which violate the Lapworth model of alternating polarities and react with electrophiles at the ipso- and a-positions ... 

The nitroaldol condensation reaction involving aldehydes and nitronates, derived from deprotonation of nitroalkanes by bases. 

In a series of reports between 1991 and 1997 Yamaguchi showed that rubidium salts of L-proline (9) catalysed the conjugate addition of both nitroalkanes [29, 30] andmalonates [31-33] to prochiral a,p-unsaturated carbonyl compounds in up to 88% ee (Scheme 1). Rationalisation of the selectivities observed involved initial formation of an iminium ion between the secondary amine of the catalyst and the a,p-unsaturated carbonyl substrate. Subsequent deprotonation of the nucleophile by the carboxylate and selective delivery using ion pair... 

The majority of recent contributions for the conjugate addition of C-H acids to a,p-unsaturated carbonyl compounds catalysed through iminium ion intermediates have come from the laboratories of Jprgensen. The ease with which 1,3-dicarbonyl compounds and nitroalkanes can be deprotonated, together with the soft nature of the nucleophile mean this is a particularly facile reaction which conveniently leads to useful precursors for further synthetic manipulation. 

The carbon nucleophiles in amine-catalyzed reaction conditions are usually rather acidic compounds containing two electron-attracting substituents. Malonic esters, cyanoacetic esters, and cyanoacetamide are examples of compounds which undergo condensation reactions under Knoevenagel conditions.115 Nitroalkanes are also effective nucleophilic reactants. The single nitro group sufficiently activates the a hydrogens to permit deprotonation under the weakly basic conditions. Usually, the product that is isolated is... 

The authors suggested that 222 operates in a bifunctional mode by hydrogenbonding activation of the nitroalkane and subsequent a-deprotonation through the basic oxazoline nitrogen providing a nucleophilic nitronate, which attacks the imine and give the observed aza-Henry adduct (Scheme 6.183) [345]. 

Fig. 28 Energy diagram illustrating the configuration curves that contribute to the deprotonation reaction of a nitroalkane. The major configurations are the reactant configuration [44], the oxyanion configuration [45], and the carbanion configuration [46]...

A kinetic study of the deprotonation-reprotonation behaviour of (4-nitrophenyl)-nitromcthane in 50% H2O-50% Me2SO mixtures promoted by bases (phenoxide and carboxylate ions, primary amines) has revealed a one-step equilibration at pH > 4.2 the equilibration in acidic media is complicated by protonation of the exocyclic nitro group.142 The results suggest that the substrate acts essentially as a nitroalkane rather than a /j-nitrotolucnc. A further study of kinetics of deprotonation of (4-nitrophenyl)nitromethane has provided evidence of a steric effect on proton tunnelling on reaction with /V -propyl-A./V-dipropylbcnziinidamidc.143... 

In cases where there is strong solvation of the carbanion, as for example hydrogen bonding solvation of enolate or nitronate ions in hydroxylic solvents, the intrinsic barrier is increased further because the transition state cannot benefit significantly from this solvation. This is the reason why AG for the deprotonation of nitroalkanes in water is particularly high, i.e., much higher than in dipolar aprotic solvents, see, e.g., entry 11 versus 15 and entry 13 versus 16 in Table 1. These solvation effects will be discussed in more detail below. 

The reason why delocalization is not more advanced is that there are constraints imposed on the transition state that prevent extensive delocalization. This was first pointed out by Kresge51 in the context of the deprotonation of nitroalkanes, but it applies to any proton transfer from carbon. The situation is represented in Equation (9) which is a more nuanced version of Equation (3) and allows for a certain degree of charge delocalization into the jt-acceptor (8Y) at the transition... 

Fig. 1 More O Ferrall-Jencks diagram for the deprotonation of a nitroalkane. The curved line shows the reaction coordinate with charge delocalization lagging behind proton transfer.

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