Nucleophilic stabilization

FIGURE 8 10 Hydrogen bonding of the solvent to the nucleophile stabilizes the nucleophile and makes It less reactive... 

Treatment of y-nitro alcohols with diethyl azodicarboxylate DEAD and triphenylphos-phine affords nitrocyclopropanes with inversion of configuration at the a-carbon via the intramolecular Mitsunobu reaction involving carbon nucleophiles stabilized by the nitro group (equation 16)28. The reaction works best with nitro compounds (pA"a < 17) and is not applicable to the sulfonyl derivatives (pATa 25). 

A similar distinction between a system with pre-electrolysis with only one electrode (in this case anodic) process, and a system with simultaneous anodic and cathodic processes (in which anode and cathode are on opposite walls of a microchannel so that each liquid is only in contact with the desired electrode potential, analogous to the fuel cell configurations discussed above) was made by Horii et al. (2008) in their work on the in situ generation of carbocations for nucleophilic reactions. The carbocation is formed at the anode, and the reaction with the nucleophile is either downstream (in the pre-electrolysis case) or after diffusion across the liquid-liquid interface (in the case with both electrodes present at opposite walls). The concept was used for the anodic substitution of cyclic carbamates with allyltrimethylsilane, with moderate to good conversion yields without the need for low-temperature conditions. The advantages of the approach as claimed by the authors are efficient nucleophilic reactions in a single-pass operation, selective oxidation of substrates without oxidation of nucleophile, stabilization of cationic intermediates at ambient temperatures, by the use of ionic liquids as reaction media, and effective trapping of unstable cationic intermediates with a nucleophile. 

Zinc metalloproteases see Zinc Enzymes) form an important class, distinguished by a strict requirement for a tightly bound mononuclear zinc ion cofactor. The role of the zinc ion in the hydrolytic mechanism is to polarize and activate both the coordinated peptide carbonyl and a coordinated solvent nucleophile, stabilizing the tetrahedral intermediate... 

Most of the known ribozymes require divalent cations, usually Mg +, which is used for proper assembly of a complex 3D structure that provides an appropriate environment for catalysis. Metal ions can also act as cofactors in the chemical reaction enabling catalysis by activation of the nucleophile, stabilization of the transition state and protonation of the leaving group in general acid catalysis [424]. Accordingly, ribozymes could be considered as metalloenzymes. This fact has suggested the use of ribozymes as sensing elements for the detection of metal ions. 

However, in the presence of a suitable Lewis base the polymerization becomes living, due to the nucleophilic stabilization of the growing cation generated by the added base. (3) Initiator, strong Lewis acid and onium salt as additive-. The previous method cannot be easily applied in polar media. In this case the living cationic polymerization is promoted by the addition of salts with nucleophilic anions, such as ammonium and phosphonium derivatives. 

Any molecule that could specifically stabilize the cation II will be a base and combine with the proton therefore, the equilibrium is displaced away from II. For other carbocations (such as the alkyl cations), the solvents interacting specifically with the positively charged species will be nucleophiles and combine with the carbocations. This relationship does not mean that carbocations cannot be nucleophilically solvated as discussed recently (34, 35). Interestingly, though, apparently n donors interact preferentially with hydrogen atoms rather than the cationic carbon (36), thus reacting as bases rather than nucleophiles (37). Also, Sharma et al. (34) concluded that nucleophilic stabilization is not the dominant solvation for carbocations in solution. In any event, nucleophilic solvation decreases rather than enhances carbocationic character. On the contrary, any specific interaction between the solvent (SOH) and the anion, such as formation of hydrogen bonds (equation 5), displaces the equilibrium of equation 4 toward formation of carbocations ... 

Similar to Cr(CO)3 complexes, less stabilized carbon nucleophiles such as MeLi and acetone enolate add irreversibly at the position ortho to chloride in (chlo-robenzene)FeCp [84]. Nucleophiles stabilized by a nitro, p-dicarbonyl, or related groups add reversibly with ultimate formation of a substitution product [66, 85]. Ketoarene complexes 35 can be prepared by addition of a malonate derivative followed by acid-induced decarboxylation [86]. 

A wide variety of nucleophile-stabilizing groups has been found compatible. They include imine, cyano, sulfonyl, nitro, and alkoxycarbonyl [143,144] as well as more esoteric substituents such as diazo [145], phosphine [146], phosphate... 

The use of carbon nucleophiles stabilized by SR groups has been a feature of sulphur chemistry for many years now, and this year has seen additional uses for these versatile reagents. Thus the carbanion CH(SPh)2 adds in a 1,2-manner to 2-methylacrolein giving the allyl alcohol (175), which is then converted to the activated diene (176) by standard methodology. The latter has been used in studies towards the total synthesis of the Rubradirin antibiotics. The related anion ArC(SPh)2 also adds to a,/3-unsaturated systems however, in the case of lactone (177) conjugate addition is observed. If the initial ion from (177) is trapped with benzylic bromides then frans-butyrolactones (178) are obtained in good yield. ... 

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