Stabilization anomeric

It is possible that simple repulsion between parallel dipoles in 92 also plays a part in the greater stability of 93. It has been shown that aqueous solvation effects reduce anomeric stabilization in many systems, particularly for tetrahydropyranosyls. 

Furthermore, it has been demonstrated in acetals of phenyl alkyl ketones that the presence of the aromatic moiety at the anomeric carbon induces a further stabilization resulting in very strong anomeric stabilization.29 This phenomenon is reminiscent of the stronger methyl substitution effects discussed above for 1,3-dioxolane and 1,3-dioxane (see also Table 1) than for alkyl ethers and alkanes. 

The ease of selective protection can be explained in terms of maximum anomeric stabilization such that both anomeric methoxy groups of the product are oriented in the axial position with respect to the central dioxane ring. All four sterically demanding alkyl substituents are then placed in the favored equatorial positions. The poor selectivity for the protection of glucose results from the existence of two pairs of trans-hydroxyl groups in this sugar. 

This results in a predicted enthalpy of formation of 16 kJ mol for l-aza-2,8-dioxabicyclo [3.3.0]octane. This value is plausibly an overestimate. We have neglected any anomeric stabilization arising from the —O—N—O—substructure. However, this effect may be shown to be small. While no species with this functionality has seemingly a measured enthalpy of formation, consider the related F—N—F substructure as found in FENFi and the enthalpy of the following equation 20 which is close to thermoneutral. 

Hydroxylating 3-phenylisoxazoline is enthalpicly the same as for cyclopentane, with an added 39 kJmol for anomeric stabilization (equation 46) °. 

MM2(91), MMX, and MM2 molecular mechanics calculations have been performed to determine the relative steric energy of (25)-2-hydroxymethyl-9-methylperhydro[2,l-h][l,3]oxazine. MM2(91) calculations predict that the major isomer should be a cis-fused conformation, overestimating the influence of anomeric stabilization, but the other calculations give more realistic predictions that the major isomer should be (2S)(5R)(9aS)-trans fused (95JOC2989). 

A PNS effect involving anomeric stabilization of a geminal dialkoxy compound has been observed when comparing kinetic and thermodynamic data of reactions 55 and 56. Reaction 55... 

This anomeric stabilization of radicals is also observed using halonitrosugars such as 1-C-nitroglycosyl halides [22] 15. Captodative stabilization of the alcoxy nitro radicals explains the radical-chain substitution with mild nucleophiles such as ma-lonate or nitroalkane anions to form 16 (Scheme 8). 

The SM2/AM1 model was used to examine anomeric and reverse anomeric effects and allowed to state that aqueous solvation tends to reduce anomeric stabilization [58]. Moreover, SM2/AM1 and SM3/PM3 models were accounted for in calculations of the aqueous solvation effects on the anomeric and conformational equilibria of D-glucopy-ranose. The solvation models put the relative ordering of the hydroxymethyl conformers in line with the experimentally determined ordering of populations. The calculations indicated that the anomeric equilibrium is controlled primarily by effects that the gauche/trans 0-C6-C5-0 hydroxymethyl conformational equilibrium is dominated by favorable solute-solvent hydrogen bonding interactions, and that the rotameric equilibria were controlled mainly by dielectric polarization of the solvent [59]. On the other hand, Monte Carlo results for the effects of solvation on the anomeric equilibrium for 2-methoxy-tetrahydropyran indicated that the AM1/SM2 method tends to underestimate the hydration effects for this compound [60]. 

In physical terms, this implies donation from the p lone pair into the antibonding o cx orbital. The oxygen atom becomes electron depleted and less basic any protonation will be at the sp2 lone pair because attack at the p orbital will diminish the anomeric stabilization.16 Conversely, the electron transfer increases the basicity of the X atom. It becomes more easily protonated, which further weakens the CX bond and encourages the X group to leave. Deslongchamps has shown that this phenomenon has important consequences in acetal chemistry (X = OR), a detailed discussion of which appears in ref. 13. 

Fig. 11.1. Parent compound of phosphonium ylides (A) and a typical phosphonium ylide (B). Below the Ph3P -CH2 conformer, which is capable of maximum anomeric stabilization, and the corresponding MO diagram.

The fact that the substituents on the side chains can control the conformation of the spiroketal centre means that it is not necessary to worry about that centre in a synthesis, provided you are trying to make the spiroketal that has the double anomeric stabilization (both oxygens axial) and that has any substituents equatorial on the rings. A recent (1997) synthesis of a single enantiomer of some fruit-fly pheromones from an aspartic acid-derived bromodiol is shown overleaf. It involves three different-sized oxygen heterocycles. 

The increase in the anomeric stabilization of the S-inside cis-fused conformer of perhydrothiazolo[3,4-n]pyridine (471) is expected from a comparison of the equilibria positions of perhydropyrido[l,2-c]-... 

The normal primary deuterium isotope effect in the first part shows that an OH bond is being broken in tile rate-detertnining step. Imidazole is loo weak a base to remove the OH proton completely so its role must be as general base catalyst. Attack on the carbonyl is the slow step with (aster breakdown of the tetrahedral intermediate arid hydrolysis of the lactone. Lactones arc hydroly,sed faster than esters because they lack anomeric stabilization (p. 1134). [ he role ttf the OH group is intramolecular nucleophilic catalyst. 

Take a look at the following reaction and note the formation of the two isomeric products. Predict, on account of relative energy calculation, the ratio of the two isomers. Please consider the anomeric stabilization arising from electron pair orbital on sulfur the same as that arising from oxygen. 

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