Stereocontrol in Reactions on Account of A 1,3 Strain

An interesting aspect of the lci/lc2 conformational change is the steric resistance offered to an approaching reagent when the substrate is a reactive species such as an enamine or enolate. This approach will be controlled by two factors (a) the stere-oelectronic effect which demands as much continuous orbital overlap as possible in the TS and (b) the steric resistance that will be offered to the reagent s approach. 

In lei (R1 = O M+ and R2 = R), there is absolutely no resistance to a reagent s axial approach and an electrophile is expected to attack C2 on the lower face to 

With R1 = H and R2 = CH3 in 2, the conformer 2a is more stable than the con-former 2c by 0.90 kcal mol-1 at 6—31G level of Hartree-Fock theory, respectively. This result may be taken to understand that the A(1,3) interaction in the conformer 2a is not significant enough to subvert the conformer distribution in favor of 2c. 

NMR studies have revealed that. vv/ -2-methylcyclohexylideneacetic acid 19 exists predominantly as the conformer 19a with the methyl group axial, whereas the corresponding tmfi-isomer 20 adopts predominantly the conformer 20a with the methyl group equatorial [17]. 

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