Acetals stereoelectronic effects

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... 

The reaction of orthoesters with Grignard reagents provides a well known route to acetals and ketals U->-2). Eliel and Nader (1) have investigated the stereochemistry of this reaction and have concluded that it is governed by powerful stereoelectronic effects. 

The first results which indicate that stereoelectronic effects play an important role in the aldol condensation were reported by Hajos and Parrish (6) who found that (a) triketone J8 cyclizes to the bicyclo[3.2.1]octane ketol on treatment with piperidinium acetate in water and (b) ketol 19 undergoes an epimerization at C-4 yielding the more stable isomeric ketol 20 on treatment with piperidine. The authors concluded that the formation of ketol 19 from 18 under kinetically controlled conditions is the result of... 

A new strategy for the synthesis of erythromycin A and closely related mac-rolide antibiotics was elaborated in our laboratory (88). This new approach to synthesis is based on the knowledge that stereoelectronic effects control the conformation of acetals. The strategy is based on the 1,7-dioxaspiro-[5.5]undecane system which was found to be conformationally rigid, existing in conformation J50 only (see Chapter 2). This is so because in this confor-mation, steric effects are at their minimum and the acetal function has... 

Acetals and Related Functions 5 B, and respectively. The remaining conformers , , and F possess a plane of symmetry. Consequently, the acetal function can in principle exist in the six different conformations A-F. Experimental evidence will be described which shows that the relative stabilities of these various conformers depend on stereoelectronic effects and the standard steric interactions. 

Stereoelectronic effects have long been recognized to influence the configuration and the conformation of acetals, particularly in carbohydrates where these effects were first discovered and discussed in terms of the anomeric and the exo-anomeric effects (1-3). The term anomeric effect introduced by Lemieux in 1958 (A) refers to the tendency of an alkoxy group at C-l of a pyranose ring to assume the axial rather than the equatorial orientation despite unfavorable steric interactions, whereas the term exo-anomeric effect also introduced by the same author (5) concerns the preferred orientation of the 0-R bond of the alkoxy group at the anomeric center. 

Stereoelectronic effects should also be observed when one or both oxygens of the acetal function are replaced by another heteroatom such as a sulfur or a nitrogen atom. Compounds having sulfur atoms will first be considered. 

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. 

The relationship between the conformation of the acetal function and its reactivity towards ozone has been described in detail (cf p. 41 ). It was shown that the insertion of ozone into the C —H bond of the acetal function to form the corresponding hydrotrioxide tetrahedral intermediate is subject to stereoelectronic control. This section deals with the next step of this reaction, i,e., the decomposition of the hydrotrioxide tetrahedral intermediate to yield the ester product. Experimental results will be presented to show that this step is also controlled by stereoelectronic effects. These results can therefore be used as evidence for the principle of stereoelectronic control in ester formation. 

Treatment of polyolefinic ketal 230 with stannic chloride in pentane gave a mixture (30% yield) of about equal amounts of the two racemic D-homoster-oidal tetracyclic isomers 231 (88). In this cyclization, the first cationic intermediate is not chiral and the two faces of the 5,6-double-bond can react with equal facility with the carbonium ion as a consequence, the product obtained (231) is necessarily racemic. The conversion of the open-chain tetraenic acetal 230 having no chiral centers into a tetracyclic system having seven such centers and producing only two (231) out of a possible 64 racemates is a striking tribute to the power of stereoelectronic effects. 

Some the best-known work of Grein and his coworkers involves the development of methods for the calculation of hyperfine coupling constants.141 More recently the focus has shifted to calculating magnetic g-tensors from highly correlated wavefunctions. Grein s current interests include the study of stereoelectronic effects (such as the anomeric and reverse anomeric effects in acetal-like systems) in organic chemistry, a topic to which he has made important contributions.142... 

D-(+)-galactose (15) is an example of the consecutive numbering of the carbon ring atoms in a monosaccharide (disaccharide see p. 253). Carbohydrates can exist in a cyclic and an acyclic structure. For this reason there is a special position in the structure of a monosaccharide, the carbon atom C-l and so called anomeric center. You can see that there is an equilibrium between er-anomer a-15 and / -anomer /3-15 of D-(+)-glucopyranose over the acyclic aldehyde structure 16. Both are cyclic hemi-acetals. The /Tanomer is the preferred conformation, but there are a few effects, like sterical or stereoelectronical effects (anomeric effect, inverse anomeric effect), which have influence on the a /i rate. 

Heterobicyclic compounds often display specific behavior in their ring-opening polymerization. This is attributed to their rigid and bulky structures which contain, in most cases, two or more asymmetric carbon atoms. Sometimes, stereoelectronic effects involving heteroatoms also play an important role in regulating polymerization processes. For example, racemic bicyclic acetals such as 6,8-dioxabicy-clo[3.2.1]octane and its derivatives often undergo stereospecific polymerization even in the presence of conventional Lewis acid initiators. 

The formation of acetals allows a remarkable degree of control over the chemistry of sugars. Apart from the simple glucoside acetal we have just seen, there are three important acetals worth understanding because of the way in which they illustrate stereoelectronic effects—the interplay of... 

A double iodoetherification of C2-symmetric acetals has been used for the desymmetrization of 1,6-dienes in an asymmetric total synthesis of rubrenolide (Equation 78) <2005AGE734>. Remarkably, four stereogenic centers have been installed in one reaction step. Stereoelectronic effects in the diastereoselective synthesis of 2,3,5-trisubstituted tetrahydrofurans via iodoetherification have been studied in detail, and I(2,4,6-collidine)2C104 proved to be an efficient reagent for highly stereoselective iodoetherifications <20010L429>. 

Selectivity can be an overriding commodity in cases where reactivity is dictated by logic and accepted concepts. Such is tte case with stannylene acetals of diols and ttialkyl-stannyl ethers of aktdiols. Enhanced nuclecqthilicity of oxygen attached to tin and well-documented stereoelectronic effects associated with methine carbon atoms of tiialkyltin ethers lead to remarkably selective reactions of 0-substitution and oxidation in polyhydroxy compounds. 

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. 

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