And the anomeric effect

Acyl protection should lead, as a consequence of neighboring-group participation and the anomeric effect, exclusively to a products. This has been proved in many experiments (Table XV) with Me3SiOTf as catalyst excellent yields could be obtained in cases where all other methods essentially failed (129). It could be shown that at least some of the reactions proceed via rapid orthoester formation (129), and this intermediate then rearranges under Me3SiOTf catalysis to the desired reaction product. 

Eliel et al. (82JA3635) examined the conformational equilibria of a number of disubstituted oxanes (Table III) by low-temperature C NMR spectroscopy (830MR94) and estimated the AG° values of 3-Me and 2-C=CH substituents (see Table I). The concentration of the axial 2-Me and 4-Me conformers, however, was so small and difficult to detect by NMR spectroscopy that they were forced to employ the use of counterpoised di-2-C=CH and ds-2-CH = CH2 groups to generate equilibria that were sufficiently balanced to measure accurately (AG° values in Table I). Eliel et al. (82JA3635) also discussed the conformational energies in terms of 1,3-diaxial interactions and the anomeric effect. 

Spiroketalization, The synthesis of talaromycin B (3) with four chiral centers by cyclization of an acyclic precursor presents stereochemical problems. A solution involves cyclization of a protected (3-hydroxy ketone with only one chiral center.1 Because of thermodynamic considerations (i.e., all substituents being equatorial and the anomeric effect), cyclization of 1 with HgCl2 in CH3CN followed by acetonation results in the desired product (2, 65% yield) with a stereoselectivity of —10 1. Final steps involve conversion of the hydroxymethyl group to ethyl by tosylation and displacement with lithium dimethylcuprate (80% yield) and hydrolysis of the acetonide group. 

In summary, these peracylated derivatives lead to conformational equilibria, except in the case where the issue is particularly obvious a-D-xylo, Ci -D-arabino, C4 configurations). The free pentoses in aqueous solution still remain to be seen. The diaxial interactions are stronger than with the acetates and the anomeric effect is weaker. Out of the eight D-pentose configurations, four of them (jS-D-arabinose, a-D-lyxose, a-D-ribose, and jS-D-ribose) lead to a conformational equilibrium. 

In the peracetylated a-D-idopyranose, steric hindrance of the axial oxygens is lessened by acetylation, and the anomeric effect is increased. This ester exists exclusively in the tetraaxial d- Ci confonnation, 237. (Durette and Horton 1971). 

In addition to steric effects and electrostatic effects, the conformational analysis of carbohydrates requires two stereoelectronic effects to be taken into consideration the gauche effect and the anomeric effect, in its various manifestations. Both of these effects can be considered as aspects of no-bond resonance. 

The majority of thermodynamic data examined in these heterocyclic systems has been concerned with their ring conformations and the anomeric effect. Much of this work is cited in Section 6.08.3. Other data has been obtained from 2-phosphoryl- and 2-thiophosphoryl-l,3-dithianes <92TL227l, 94JOCi672> and 2-phosphoryl- and 2-thiophosphoryl-1,3-dioxanes <93PS(74)3il>. 

The estimated free-energies for both chair conformations of the free aldopyranoses were then calculated by summation of the various steric interactions and the anomeric effect of the anomeric hydroxyl group. The energies calculated are given in Table IV (see p. 85), together with the conformations predicted and those indicated by experiment. When the free-energy difference between the two ehair forms was less than 0.7 kcal.mole", both conformers were considered to be present in comparable amounts at equilibrium. 

Theoretical studies of tetrahedral carbon species have played an important role in the formulation of ALPH and the anomeric effect. Similarly, molecular-orbital calculations have been the touchpaper for development of the stereoelectronic effect in phosphorus chemistry. Early theoretical calculations indicated the influence of the anomeric and gauche effects in phosphates (Newton, 1973). But without doubt, the foray of Lehn and Wipff (1975) into this field provided the inceptive piece of research that was the impetus for a series of studies resulting in the proposition of a stereoelectronic theory with a far-reaching impact on nucleophilic substitution reactions at phosphorus. 

Revision of the mechanism of acetal formation and the anomeric effect. 

The conformational analysis by MM2 calculations indicates a preference for the twist-boat conformation in 2,3-dihydro-5//-l,4-dioxepin (47) and for a chair in 6,7-dihydro-5//-l,4-dioxepin (46) as well as in the methoxy derivative (65). It has been suggested that the stability of the different conformations should be governed by the conjugation of the oxygen atoms with the n system, in (46) and (47), by this conjugation and the anomeric effect in (65). The barrier for the chair-twist boat interconversion has been calculated to be 2.50 kcal mol" in (47) and 3.78 kcal mol" in (65) <89JOC6034>. 

This conformation is situated in the low-energy zone in which van der Waals interaction and the anomeric effect are optimized. An intramolecular hydrogen-bond between 0-3 and the ring 0-5 of anotoer residue provides additional stabilization (0-5... 0-3 2.75 A). This linkage is standard in cellulose chains with two-fold symmetry. 

The reaction is thermodynamically controlled, and the major product is the most stable glycoside for the reaction of D-glucose with methanol this is methyl a-D-glucopyranoside. Six-membered rings are more stable than five-membered ones, and the anomeric effect stabilizes an axial —OCH3 group. 

Andersen CB, Sepp DT (1968) Conformation and the anomeric effect in 2-oxysubstituted tetrahydropyrans. Tetrahedron 24 1707-1716... 

Fuchs B, Ellencweig A, Tartakovsky E, Aped P (1986) Solvent polarity and the anomeric effect. Angew Chem Int Ed Engl 25 287-289... 

Chattopadhyaya et al. [8] have shown based upon thermodynamic estimates on a set of four isomeric 273 -deoxynucleosides that the net result of the gauche effect and the anomeric effect is of major importance in determining the overall furanose conformation. Many qualitative studies have been conducted [83-88] to understand how the electronic nature, protonation state [89], bulkiness or substitution pattern [90-95], and configuration of the nucleobases [96-115] or Cl substituent [116] modulate the sugar conformation in nucleosides and nucleotides, as well as furan-osides [117-121]. The conformational analysis [122] in solution of a dimer containing a 4 -oxofuran derivative [123], based upon the analysis of vicinal Jhh. has shown that the modified nucleoside adopts exclusively (89 %) the S-type puckered geometries, as a result of the cooperative drive by the 05 -C4 -04 anomeric effect and the [03 -C3 -C4 -04 ] gauche effect. 

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