Conformations, anomeric effect barrier

The first precise evaluation (2A, 25) of both the anomeric and the exo-anomeric effects was obtained by studying 1,7-dioxaspiro[5.5]undecane (9) (Fig. 2). With this system, conformational analysis by low temperature nmr spectroscopy was possible because each conformational change involves a chair inversion which has a relatively high energy barrier. The steric effect could also be easily evaluated, and by adding appropriate alkyl substituents, it was theoretically possible to isolate isomeric compounds which would exist in different conformations. 

As we have seen, the anomeric effect confers a double-bond character to each C—0 bond of conformer D the energy barrier for a C —0 bond rotation in acetals must therefore be higher than that observed in simple alkanes. Borgen and Dale (41) may have provided the first evidence for this point by observing that 1,3,7,9-tetraoxacyclododecane (37) has a much higher conformational barrier (11 kcal/mol) than comparable 12-membered rings such as cyclododecane (7.3 kcal/mol (42) or 1,4,7,10-tetraoxacyclododecane (5.5 and 6.8 kcal/mol (43)). It was also shown that the two 1,3-dioxa groupings in 37 exist in a conformation identical to that of dimethoxymethane, i.e. the conformation D. 

Anet and Yavari (44) have studied chloromethyl methyl ether by low temperature proton nmr spectroscopy. Their results show that this compound exists in the gauche conformation 38 and they observed a barrier of 4.2 kcal/mol for the rotation of the O-CHjCl bond. This barrier is appreciably higher than that expected on the basis of steric repulsion alone. A rough estimate of the steric barrier is 2 kcal/mol, and they concluded that the anomeric effect increases the barrier to rotation of the O-CHgCl bond by approximately 2 kcal/mol. 

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>. 

Lemieux, R. U., and S. Koto The Conformational Properties of Glycosidic Linkages. Tetrahedron 30, 1933 (1974) Bailey, W. F., and E. L. Eliel Conformational Analysis. XXIX. 2-Substituted and 2,2-Disubstituted 1,3-Dioxanes. The Generalized and Reverse Anomeric Effects. J. Amer. Chem. Soc. 96, 1798 (1974) Anet, F. A. L., and I. Yavari Generalized Anomeric Effect and Barrier to Internal Rotation about the Oxygen-Methylene Bond in Chloromethyl Ether. J. Amer. Chem. Soc. 99, 6752 (1977). 

This interpretation could be complicated by the conformational equilibrium Hs/ H4 which gives to 3,4,6-tri-O-acetyl-D-glucal 10, for instance, a 40% contribution of the (d) conformer with all its substituents axial. A vinylogous anomeric effect could explain this unusual distribution [28]. However, assuming a lower energy barrier for this conformer equiUbrium in comparison to the subsequent reactions, the Curtin-Hammett principle can be apphed and the product ratio will be governed by the activation energy of the electrophilic addition, rather than by the actual concentration of conformers. 

In comparison with previous plots of this section, the no-crco anomeric interaction of Fig. 3.65 can be seen to be a rather typical example of hyperconjugative donor-acceptor interactions. Consequently, there seems to be no valid reason to invoke a special effect for the conformational preferences of sugars, obscuring their essential conformity with a unified donor-acceptor picture of ethane-like rotation barriers. 

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