Conformational analysis destabilization energies

Spherical polar coordinates are used for conformational representation of pyranose rings in the C-P system. Unlike the free pseudorotation of cyclopentane, the stable conformations of cyclohexane conformers are in deeper energy wells. Even simong the (less stable) equatorial (6 = 90 ) forms, pseudorotation is somewhat hindered. Substitutions of heteroatoms in the ring and additions of hydroxylic or other exocyclic substituents further stabilize or destabilize other conformers compared to cyclohexane. A conformational analysis of an iduronate ring has been reported based on variation of < ) and 0 (28), and a study of the glucopyranose ring... 

Corey and Feiner have developed a computer program (LHASA) for conformational analysis and for determining the destabilization energies (Ep) in substituted cyclohexane derivatives. In the following discussion, we will adopt their A, G and U designations and use the corresponding values for evaluating steric interactions. 

From the analysis of the factors thus far considered, boat-boat conformation 2c should be stabilized by 1,3-diaxial repulsion. The introduction of bulky substituents both in endo-3 and in endo-1 positions (13) leads to the predominance of the double boat conformation 13c in the equilibrium (27,28). Analogously, the introduction of four bulky substituents in exo-2,4,6, and 8 positions (14) could lead to the destabilization of the chair form for each of the six-membered rings and to a preference for boat-boat conformation 14c because of the strong 2 4 and 6 8 repulsion of the substituents. However, compounds of this kind have not been studied yet. It is necessary to mention that the boat-boat conformation should correspond in fact to a maximum on the energy curve, while a twist-twist, TT, form approximated by 15 would be expected to correspond to a minimum. In the TT conformation the flagpole and eclipsed interactions are diminished (the BB conformation is significantly more flexible than the CB one and is easily twisted). 

For a diene with the auxiliary at C2, C2-Xc bond rotation will populate two rotational isomers unless the auxiliary is C2-symmetric, in which case the two rota-mers are identical (Figure 6.16a) or unless there is a substituent either at Ci, cis to the auxiliary, or at C3, in which case one of the conformers may be destabilized by repulsive van der Waals interactions (Figure 6.16b, R H). When the auxiliary is at Cl, a similar situation exists a C2-symmetric auxiliary has only one conformational isomer possible (Figure 6.16c), but an otherwise unsubstituted diene will have two rotational isomers of unequal energy (Figure 6.16d). Thus, for a diene with the auxiliary at C2, a C2-symmetric auxiliary would seem to have an advantage [199]. When the auxiliary is at Ci, the two conformers are unequally populated as long as there is no other substituent at Ci. A similar analysis could be made for other substitution cases, but this analysis covers the examples which follow. 

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