Hydrolysis stereoelectronic effects

Besides di- and poly-saccharides, zeolites have been applied for hydrolysis of simple glycosides as described by Le Strat and Morreau.132 Methyl a- and /i-D-glucopyrano-sides were treated with water in the presence of dealuminated HY faujasite with an Si/Al ratio of 15, at temperatures ranging between 100 and 150 °C. It was observed that the reaction rate for the (i glycoside was about 5-6 times higher than that for the oc anomer, a result that might arise from the shape-selective properties of the zeolite and stereoelectronic effects on the surface of the solid. 

C. Moreau, J. Lecomte, S. Mseddi, and N. Zmimita, Stereoelectronic effects in hydrolysis and hydrogenolysis of acetals and thioacetals in the presence of heterogeneous catalysts, J. Mol. Catal. A Chem., 125 (1997) 143-149. 

The first indication that this relationship can be a very simple one arose as part of an investigation of stereoelectronic effects in acetal hydrolysis. According to Deslongchamps (1983) theory of stereoelectronic control (see also Sinnott, 1988), the orientation of lone-pair electrons can control reactivity in appropriate systems. In its original form the theory suggested... 

P. Deslongchamps, Stereoelectronic Control in the Cleavage of Tetrahedral Intermediates in the Hydrolysis of Esters and Amides , Tetrahedron 1977, 31, 2463 - 2490 P. Deslongchamps, Stereoelectronic Effects in Organic Chemistry , Pergamon Press, Oxford, 1983. 

This Chapter deals with the stereoelectronic effects which control the cleavage of tetrahedral intermediates during the formation or the hydrolysis of an ester. Since these effects are also operative in the ester function itself, a discussion of the functional group will first be presented. 

We have presented experimental results which demonstrate the influence of stereoelectronic effects on the configuration and the conformation of the acetal function. A pertinent question which follows is whether or not these stereoelectronic effects play a similar role in the formation and in the hydrolysis of this functional group. 

The formation or the hydrolysis of an acetal function proceeds by the mechanism described in Fig. 16 in which oxonium ions and hemiacetals occur as intermediates. It has also been established (76) that the rate determining step in acetal hydrolysis is generally the cleavage of the C—bond of the protonated acetal 100 to form the oxonium ion 111, This ion is then rapidly hydrated to yield the protonated hemiacetal 112 which can give the aldehyde product after appropriate proton transfers. It is pertinent therefore to find out if stereoelectronic effects influence the rate determining step (110 111) of this hydrolysis reaction. 

Lehn and Wipff (72) and Gorenstein and co-workers (73-80) have proposed on the basis of molecular orbital calculations that stereoelectronic effects similar to those observed in esters and amides play also an important role in the hydrolysis of phosphate esters. For instance, calculations suggest that the axial P — OR bond in the trigonal bipyramid conformation 120 is weaker than that in the conformation 121 because in the former, the oxygen atom of the equatorial OR group has an electron pair anti peri planar to the axial P — OR bond. Experimental results tend to support this interesting proposal but additional experiments are needed before unambiguous conclusions can be reached (81). 

It has been pointed out in Chapter 2 (p. 39) (see also 1-4) that there is good evidence which indicates that in the hydrolysis of B-glycosides by lysozyme, the substrate must take a boat conformation in order to produce the half-chair oxocarbonium ion 0+2- -3i)- Lysozyme is therefore a good example which provides evidence that stereoelectronic effects play a key role in enzymic hydrolysis. 

As for hydrolysis of disaccharides maltose and cellobiose, the (Ha anomeric ratios are in agreement in terms of stereoelectronic effects which are, according to the... 

The effect of substituents on the stereoselectivity has been studied in the acid-catalyzed hydrolysis of a series of aryloxiranes. Work on the influence of temperature on the steric course of the reaction has demonstrated that the tendency towards retention is explained by the high degree of carbocationic nature in the transition state leading to the cis products, the favorable entropy content of the transition state of cis addition, and the relatively low enthalpy barrier of the benzyl C-0 bond. At the same time, almost complete tram selectivity can be observed in aliphatic and cycloaliphatic oxiranes and ionization of the C-0 bond is associated with high enthalpy values. Attempts have been made to separate the inductive, conformational, and stereoelectronic effects. 3,4-Epoxytetrahydropyran was used to study the inductive effect while the corresponding cis- and trans-methyl derivatives were employed to examine the stereochemical and conformational factors. ... 

Selective deprotection of acetals—determined by the relative rate of hydrolysis as influenced by steric, inductive, and stereoelectronic effects... 

P. Deslongchamps, Y. L. Dory, and S. Li, 1994 R.U. Lemieux award lecture hydrolysis of acetals and ketals. Position of reaction states along the reaction coordinates, and stereoelectronic effects, Can. J. Chem., 72 (1994) 2021-2027. 

Let us consider the reverse of acetal formation, i.e., acid hydrolysis of an acetal within the ambit of stereoelectronic effects and explore the underlying features. We begin by understanding the conformational profile and the associated conformational effects by representing the acetal in such a way that it appears to be part of a cyclohexane chair. In doing so, we understand the geometrical relationship of various bonds on this ring system much better. 

The acetal RCH(OMe)2 can have a total of nine conformers, 30a-30i. We may ignore the broken red bonds, which are included to allow a quick conformational match with that of the cyclohexane chair and, thus, ascertain the geometrical relationships rather easily. The conformers 30a and 30e have two methyl groups within van der Waals distance and, hence, their contributions to the overall conformational equilibrium will be small, if not zero. We can therefore eliminate these conformers from further discussion. The conformers 30b and 30d, 30c and 30 g, and 30f and 30 h are mirror images and, thus, we need to consider only one conformer of each pair. Thus, we are left with four distinct conformers, namely 30b, 30c, 30f, and 30i, to consider for acid hydrolysis. The relative contributions of these conformers could be estimated from the understanding that they are laced with two, one, one and zero stereoelectronic effects, respectively. The conformers 30b and 30i are, respectively, the most contributing and the least contributing. The conformers 30c and 30f contribute at the medium level. 

The reaction of D-gluconolactone 49 with 018-labeled hydroxide ion under stereoelectronic control (which is axial attack) will furnish 50. Note that the crc (, ri bond formed is antiperiplanar not only to an electron pair orbital on the resultant oxy anion, but also to the axial electron pair orbital on the ring oxygen. This reaction is reversible because the crc G n can also cleave very rapidly with the assistance of the same two stereoelectronic effects that facilitated its formation in the first place. Intramolecular proton transfer culminating in the transformation 50 —> 51 is also reversible. The ctc oh bond in 51 cannot cleave because it is antiperiplanar to only one electron pair orbital on the oxy anion [O ]- and, thus, 54 that retains the labeled oxygen will not form. In other words, if the hydrolysis reaction is interrupted (quenched by an aqueous acid) before completion and the unreacted D-gluconolactone is examined for the presence of O18, it will be discovered to be absent. 

An argument similar to that for the hydrolysis of D-gluconolactone leads us to 59 as the final product, wherein the label O18 has been incorporated. The transformation 57 —> 60 is not allowed for the lack of support by the requisite two stereoelectronic effects. Conformational ring flip from 57 to 61 is energy requiring. It may therefore be claimed not to compete with the fast cleavage of 57 to 58 because the latter is supported by two stereoelectronic effects. Let us see the turn of events assuming that the said conformational flip does compete and 61 is indeed formed. 

The importance of stereoelectronic effect in orthoester hydrolysis could be gleaned from the reaction of 85. Should the stereoelectronic effects not be invoked, the reaction could generate all three different products, 89-91. When Ri and R2 are same, there will be only two products, 89 and 90. We shall learn below from a meaningful consideration of the prevailing stereoelectronic effects that only the 89-like product is expected to predominate. 

Let us examine each step of the orthoester hydrolysis under the operating stereoelectronic effects that vary with the variation in the conformational profile. Consider the acetal 92 and the nine well-defined conformers 92a-92i. The con-formers 92c and 92e suffer from severe steric interactions between the methyl groups as shown and, hence, their concentration at equilibrium should be expected to be negligible. Likewise, conformers 92g-92i also suffer from severe steric interactions between the methyl of the axial methoxy group and the axial hydrogen atoms on ring positions 4 and 6 as shown for 92 g. The equilibrium concentration of each of these conformers also should be expected to be negligible like those of 92c and 92e. We may eliminate all these conformers from further discussion. 

The loss of an alkoxy group, after protonation, is the starting point of hydrolysis. An orthoester can provide for this loss to take place with the assistance from one or two stereoelectronic effects, the latter being obviously favored over the former. The conformer 92d does not allow any stereoelectronic effects. This conformer may therefore be treated as the slow reacting or even as the neutral conformer. This prediction has been verified experimentally by studying the hydrolysis of 93, a rigid 92d conformer, which was found to be stable to the normally employed mild acidic conditions for orthoester hydrolysis [2-5]. Therefore, the conformer 92d is also eliminated from further discussion. 

Again, out of 92b —> 95a and 92f > 95b, the latter transformation ought to more efficient than the former for retaining one stereoelectronic effect. Thus, the orthoester 92 should undergo hydrolysis via the conformer 92f predominantly. 

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