Severe 1,3-diaxial interactions

It is possible to change the stereochemical result of the alkylation by replacing the 3-ketal protecting group with a A -enol ether. This structural change eliminates a severe 1,3-diaxial interaction to a-face methylation and results in the formation of the 5a-methyl steroid (15) in about 35% yield, ... 

Other examples of the formation of six-membered rings by means of an intramolecular alkylation of an ester enolate are given in Table 7. Entry 6, i.e., stereoselective transformation of the epoxy ester into the cyclohexane derivative, should be discussed briefly as a representative for the other cases. The probable reason for the unexpectedly high selectivity i.e., the nonappearance of the diastereomer 8, can be demonstrated by the two transition-state-like conformations 9 and 10. 9 displays a very severe 1,3-diaxial interaction in comparison to 10, thus, formation of the diastereomer 7 from conformation 10 is highly favored113. 

The large energy difference between conformations is due to the severe 1,3 diaxial interaction between the two methyl groups. 

Beckett and coworkers have also discovered that protonation reduced the population of the conformer with C5-axial methyl to less than 50 % of the total [5-7]. Only the conformers 5a and 5b (5a 5b = 43 57) were detected in the case of the N-ethyl salt 5. The increased interaction of the C5-axial-methyl group with the axial hydrogen atom on the nitrogen as against the electron pair orbital in 4a is considered as the primary cause for the observed shift in the conformer distribution. The conformers 5c and 5d are destabilized due to severe 1,3-diaxial interactions as shown. The conformer 5d is destabilized by A(1,2) strain as well. 

K+ as discussed above. A 2p-methyl group occupies the axial position in which it is free from interaction with the ion pair, i.e., devoid of A(1,2) interaction but in severe 1,3-diaxial interaction with the nearby angular methyl group. 

The H s and CH3 of the sp3 hybridized C have severe 1,3-diaxial interactions with the two other axial H s. 

Finally, we compare both chair drawings and determine which one has fewer or less severe 1,3-diaxial interactions. In the first drawing, both substituents occupy axial positiorrs, but in the second drawing, both substituents occupy equatorial positions. As such, the latter is more stable, since it lacks 1,3-diaxial interactions. 

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