Reversibility of nucleophilic attack

The nucleophilic attack at the carbonyl ligand is believed to induce the increase in the electron density at the metal and the oxygen atom. Such an increase would contribute to destabilization of the product complex. Therefore, the presence of more electron-withdrawing auxiliary ligand(s) is advantageous to delocalization of the electron density on the metal. A strategy to divert the charge on the 

Similarly, thermodynamically unfavorable formyl ligand formation by the attack of hydride compounds at the coordinated carbonyl was often facilitated by intra- and intermolecular metal coordination with the oxygen of the CHO ligand, as exemplified in Eqs. 8.3 and 8.4 [16d,e,h]. 

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Hydroxycrinamine methiodide (258) and precriwelline (243) undergo this same type of interconversion. The existence of two isomeric forms for pretazettine (242) and precriwelline (243) is attributed to the presence of an iV-methyl group and of hydroxy group, each capable of nucleophilic attack on the carbonyl of the intermediate amino aldehydes 255 and 256, respectively. In the light of the complete reversibility of the isomerization of pretazettine to the metho salt of haemanthidine (257), the inversion of the C-6a hydrogen of pretazettine, as required by structure 254 which should be revised to 242, would seem to be mechanistically inexplicable. 

Reversible changes in the electronic and NMR spectra of [Pt(bpy)2l in the presence of OH or MeO led to the suggestion that nucleophilic attack on the ligand was occurring (19, 71,305) in view of the formation of outer-sphere (494) and 5-coordinate complexes (557) by attack at the metal, these results are best reinterpreted in terms of nucleophilic attack at Pt (244, 677). 

Ethyl rhenlumpentacarbonyl has been reacted with various metal hydrides in acetonitrile 158). The observed products were heterobimetallic compounds, although a solvated rheniumtetracarbonyl acyl complex was detected [Eq. (47)]. If the metal hydride is in excess, the rate-determining step is formation of the propionyl complex. The reaction was subsequently found to be first order in both the propionyl complex and the metal hydride. The second-order rate constants were measured and were found to be the reverse of the order of the acidities of the transition metal hydrides, which implies that the hydrides react as nucleophiles with the propionyl complex. In a separate experiment, [Re(COEt)(CO)j] was found to react with [Re(H)(CO)j] only after carbonyl dissociation, implying that the metal and not the acyl carbonyl is the site of nucleophilic attack by transition metal hydrides on acyl complexes. 

The polarographic reduction of benzo[h]quinolizinium salts varied with pH. At pH 1.9 to 7 two waves were observed, the first (half-wave —0.807 V) a one-electron reversible reduction, the second (half-wave —1.022 V) irreversible and diffusion controlled. The proposed pathway is shown in Eq. (46). The reduction in basic medium also had two waves (half-wave potentials about — 1.5 and — 2.2 V) due to the reduction of aldehyde 103, a known product of nucleophilic attack at position 6 in benzo[h]quinolizinium salts. The changes in reduction potential produced by substituents on the benzo-[hjquinolizinium ion were examined (19 examples).123 Various explanations based on inductive and mesomeric effects were offered for observed variations. 

Figure 2.4 The illustration of microscopic reversibility for nucleophilic attack.

If the rate of nucleophile attack governs the product distribution (the nucleophilic attack is not reversible at the given temperature), the major product will be the 1,2-addition product that results from Nu attack at the greatest partial plus (kinetic control. Section 2.6). However, if the addition of the nucleophile is reversible (higher temperature or the Nu is a good L), then the 1,4-addition product will be formed because the more substituted double bond is the more stable product (thermodynamic control. Section 2.6). Suspect kinetic control if the reaction temperature is significantly below 0°C. Diene example (AdE2) ... 

In the following, examples of /I-carbon elimination when A = O are shown. The reaction is observed in the Pd-catalyzed reaction of fert-alcohols. Conversion of tert-alcohols to ketones occurs via their Pd-alkoxides 49 and the reaction can be understood by elimination of j6-carbon. Fission of a carbon-carbon bond occurs. It should be noted that jS-carbon elimination can be regarded as a reverse process of nucleophilic attack to the carbonyl group by R-Pd-X (see Chapter 3.7.2). As an example, Pd-catalyzed reaction of a,Q -dimethylarylmethanol 50 with bromobenzene is explained by elimination of jS-carbon of the arylpal-ladium alkoxide 51 to generate the diarylpalladium intermediate 52. Its reductive elimination affords 2-phenylbiphenyl (53) and acetone [41]. Similarly, Pd(II)-promoted reaction of the cyclobutanol 54 to give the unsaturated ketone 56 can be understood by elimination of j6-carbon from 55 and subsequent jS-H elimination [42],... 

Reversibility is also not anticipated for unsymmetrical alkenes such as gem-disubstituted alkenes. As is discussed in the following section, the cationic intermediates in such reactions ate highly asymmetric, with much of the positive charge on the carbon atom and relatively little on the bromine. Since reversibility implies nucleophilic attack of bromide ion on the bromine in the intermediate, the smaller the charge on bromine, the less likely is that nucleophilic attack. For further discussion, see reference 60. 

More recently, oxidative aminations of vinylarenes with amides and imides have been reported by Stahl. - In this case, the regioselectivity of the process depends on tiie presence or absence of a tertiary amine additive. As shown in Equation 16.117, the 1,1-disubsti-tuted olefin is formed in the presence of amine, but a 1,2-disubstitued olefin is formed in the absence of amine. This change in regioselectivity is proposed to arise from the degree of reversibility of the addition of the nucleophile to the coordinated vinylarene in the presence and absence of base. As shown in Scheme 16.31, the kinetic site of nucleophilic attack is proposed to be the internal carbon, but the thermodynamic site of attack is proposed to be the terminal carbon. The thermodynamic site of attack is proposed to be the terminal carbon because attack at this position forms an ti -benzyl complex. In the presence of base, the kinetic product is rapidly deprotonated, and the 1,1-disubstituted olefin is formed. In the absence of base, the deprotonation step is slow enough that the thermodynamic product of attack is generated. 

The rate of nucleophilic attack in an Sn2 reaction often depends upon the counterion of the nucleophile. For example, when the counterion isLi, the order of reactivity for the reaction of halogen nucleophiles with methyl brosylateis b > Br" > Cl. The order of reactivity is reversed when the counterion is tetrabutylammonium. Why ... 

All these facts—the observation of second order kinetics nucleophilic attack at the carbonyl group and the involvement of a tetrahedral intermediate—are accommodated by the reaction mechanism shown m Figure 20 5 Like the acid catalyzed mechanism it has two distinct stages namely formation of the tetrahedral intermediate and its subsequent dissociation All the steps are reversible except the last one The equilibrium constant for proton abstraction from the carboxylic acid by hydroxide is so large that step 4 is for all intents and purposes irreversible and this makes the overall reaction irreversible... 

Substitution Reactions on Side Chains. Because the benzyl carbon is the most reactive site on the propanoid side chain, many substitution reactions occur at this position. Typically, substitution reactions occur by attack of a nucleophilic reagent on a benzyl carbon present in the form of a carbonium ion or a methine group in a quinonemethide stmeture. In a reversal of the ether cleavage reactions described, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers by acid-catalyzed etherifications or transetherifications with alcohol or phenol. The conversion of a benzyl alcohol or ether to a sulfonic acid group is among the most important side chain modification reactions because it is essential to the solubilization of lignin in the sulfite pulping process (17). 

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