Vinylogous anomeric effects

D. P. Curran and Y. Suh, Selective mono-Claisen rearrangement of carbohydrate glycals. A chemical consequence of the vinylogous anomeric effect, Carbohydr. Res. 777 161 (1987). 

A C(6) donor substituent exerts a similar enhancing efiect on the rate of the Claisen rearrangement, though somehow less pronounced than the rate-accelerating effect of the 2-silyloxy substituent (approx. 1.4 kcal mol" ). As Curran and coworkers reported, " this vinylogous anomeric effect of the C(6) donor substituent is especially effective in glycal systems. The energy of the TS is decreased by assist-... 

The observation that L-arabinal adopted the conformation exclusively and that the and conformations of o-glucal were comparably populated led Curran and Suh" to propose a vinylogous anomeric effect , similar to the anomeric effect. Additional stabilisation of an electronegative substituent in an axial orientation was available from a p-type lone pair on oxygen, separated by a double bond, via overlap of the C X a orbital and v /2 of the enol ether (Figure 6.70). No experimental estimates of its magnitude are available, but it is likely to be smaller than the anomeric effect itself, not least because any electrostatic component is much smaller. 

Figure 6.70 The vinylogous anomeric effect, (a) Experimental evidence, (b) Cartoon of overlap of v /2 for an enol ether with the C3-X a. Different sizes of orbitals give an indication of coefficients. A valence bond representation of the effect is also shown.

A substituent-controlled "mono-Clatsen" rearrangement was also employed as a key reaction in the construction of chiral intermediates for the synthesis of pseudomonic acids from diacetyl-L-arabinal418. The acetate groups of the starting material are chemically differentiated by virtue of the accelerated rate of the first Claisen rearrangement (ascribed to a vinylogous anomeric effect). 

Figure 6.79 Vinylogous anomeric effect, caused by (n-ir) a interactions, stabilizes axial conformers in glycals.

Figure 6.80 Structural consequences of the vinylogous anomeric effect.

Katritzky, A. R., Steel, P. J., Denisenko, S. N. (2001). X-Ray Crystallographic Evidence for a Vinylogous Anomeric Effect in Benzotriazole-substituted Heterocycles. Tetrahedron, 57,3309-3314. 

Figure 9.21 Connection between the vinylogous anomeric effect and substituent effects in the Claisen rearrangement.

Curran proposed a vinylogous anomeric effect concept to explain the observed rate difference of the Ireland-Claisen rearrangements of dihydropyran 152 and cyclohexene system 155. Oxygen attached to Ce is proposed to stabilise the polar Ireland-Claisen intermediates 160-161 which contribute to a faster rate of reaction. ... 

The prevailing principle has been termed vinylogous anomeric effect as a molecular orbital rationalization may be provided by a tt a interaction in analogy to the anomeric effect [26]. Moreover, the vinylogous anomeric effect, which was independently introduced by Denmark et al. to explain the unusual diaxial conformation of cyclic a-chloroketoximes [27], also seems to account for conformational preferences of certain glycals in the ground state [22c]. 

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. 

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