Nucleophilic attack intimate mechanisms

The effect of conformation on reactivity is intimately associated with the details of the mechanism of a reaction. The examples of Scheme 3.2 illustrate some of the w s in which substituent orientation can affect reactivity. It has been shown that oxidation of cis-A-t-butylcyclohexanol is faster than oxidation of the trans isomer, but the rates of acetylation are in the opposite order. Let us consider the acetylation first. The rate of the reaction will depend on the fiee energy of activation for the rate-determining step. For acetylation, this step involves nucleophilic attack by the hydroxyl group on the acetic anhydride carbonyl... 

At a molecular level, the intimate mechanism for the water-gas shift reaction with 4.1 as the precatalyst is not known in any detail. In the conversion of 4.1 to 4.12, the evolution of hydrogen is probably indicative of the intermediacy of a hydrido complex. Similarly, in the conversion of 4.13 to 4.1, where HI and C02 are eliminated, nucleophilic attack on coordinated CO may be involved. Although these mechanistic conjectures are plausible, there is no direct evidence to support them. 

The Wacker process was a major landmark and a great push towards the development of homogeneous catalysis. The mechanism of acetaldehyde formation differs fundamentally from the other oxidation processes as O2 itself is not directly involved. As is clear from Figure 28 the actual oxidant is Pd(II) which is reduced to Pd(0). The intimate pathway of the reaction involves nucleophilic attack and was the subject of much debate. 

A number of intimate mechanisms have been found for the oxidative addition reaction, including Sn2 nucleophilic attack, as in the addition of Mel to Rh(I) (Section 4.2.5). 

Although the mechanism of the Mukaiyama reaction is not yet fully understood, several points have now been firmly established (a) a Lewis acid enolate is not involved (b) the Lewis acid activates the carbonyl group for the nucleophilic addition and (c) the Si—O bond is cleaved by nucleophilic attack of the anionic species, generally halide, on silicon. Point (a) has been established by the use of INEPT- Si NMR spectroscopy. Moreover, trichlorotitanium enolates have been synthesized, characterized and shown to give a completely different stereochemical outcome than the TiCU-mediated reactions of silyl enol ethers. Complexes between Lewis acids and carbonyl compounds have been isolated and characterized by X-ray crystallography and recently by NMR spectrometry. On the basis of these observations closed transition structures will not be considered here open transition structures with no intimate involvement between the silyl enol ether and the Lewis acid offer the best rationale for the after the fact interpretation of the stereochemical results and the best model for stereochemical predictions. 

Another product formed by the reaction of bromine with cyclohexene in acetic acid is tra s-l-acetoxy-2-bromocyclohexane. The yield of this product varies with the concentration of added LiBr (with iorric strength held constant). With [LiBr] = 0, Brown and co-workers found that the product mixture consisted of 27% 1,2-dibromo and 73% l-acetoxy-2-bromo adducts. At [LiBr] 0.1 M, 90% of the product was 1,2-dibromocyclohexane and only 10% was the l-acetoxy-2-bromo derivative. Based on the conclusion that the low a-sec-ondary deuterium KIE requires a nucleophilic (not electrophilic) role for Br, Brown and co-workers proposed the detailed mechanism shown in Figure 9.5. Here, CTC is a charge transfer complex IIP and IIP are intimate ion pairs SSIP and SSIP are solvent-separated ion pairs DI is a dissociated ion and SOH is a hydroxylic solvent. The key feature of the mechanism is the necessity for Br migration to occur in the rearrangement of IIP to IIP so that backside attack can produce the dibromo product. The SSIP can rearrange to SSIP, but the latter must then reorganize to form IIP (so that the Br is inside the solvent shell) before nucleophilic attack can occur. Added Br can react with the CTC or with IIP to produce the dibromo product. 

Since ion pairs are undoubtedly important species, the question has arisen as to whether they might be intermediates in all nucleophilic substitution processes. R. A. Sneen and H. M. Robbins suggested that ion pairs might not only be involved in SnI and borderline processes but also in displacements exhibiting the stereochemical and kinetic characteristics of the Sn2 process. They suggested the scheme shown below, in which SOH is a hydroxylic solvent and Nu" is a nucleophilic anion. In this mechanism, reactions with Sn2 characteristics are postulated to occur by nucleophilic attack on the intimate ion pair. 

The importance of the intimate mechanism was further emphasized by the unexpectedly low stereoselectivity observed in the reduction of 22 by superdeuteride, LiEtsBD. A 55/45 mixture of endolexo reduction products was obtained, in contrast to most other nucleophiles (including UBD4) which stereospecifically yield exo products. Presumably, with the highly reactive trialkylborohydride reagents initial hydride attack occurs at a CO ligand, giving a Fe-CHO intermediate, followed by transfer to the dienyl ring. A similar mechanism has recently been proposed to explain the stereochemistry of reduction of acyclic dienyl cations. 

As intimated at the beginning of the previous section, discussion of the mechanisms of reactions of nucleophiles with iron(ii)-di-imine complexes continues to flourish. The main question is whether nucleophiles such as hydroxide, methoxide, or cyanide attack at the central metal atom or at the co-ordinated di-imine ligand. The original assumption of direct attack at iron in complexes of the [Fe(phen)8] + type was questioned several years ago. Since then a considerable body of evidence has been presented in support of initial attack at the ligand but a body of opinion remains that is sceptical of such a mechanism. 

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