Evans. Breit Conformational Analysis: Cyclic Systems-4 Chem 206 Monosubstituted Cyclohexanes: A Values A Values depend on the relative size of the particular substituent △7 R△G°=- reinKe a Me -axial has 2 gauche butane interactions more than Me-equatorial Expected destabilization: s 2(0.88 )kcal/mol =-1.8 kcal/mol; A-Value 1.74 180 5.0 Observed: 1.74 kcal/mol The relative size"of a substituent and the associated A-value may not correlate For example, consider the -CMe 3 and-SiMe 3 substituents. While the-SiMe 3 ent radius is has a smaller A-value H a The A-Value, or-AG, is the preference of the substituent for the Me equatorial position Table 3.6. Conformational Free Energies(-AG )for ubstituent Groups Substituent -G°(kcal/mol)Ref. A-Value 4.5-5.0 2.5 1.1 Can CH a The impact of double bonds on A-values Lambert. Accts. Chem. Res. 1987. 20. 454 一C≡CH CAH -CN 0.15-0.25 A-value substituent AG° OH (aprotic solvents) OH (proti R 08 -OCH R=OMe HgB R=OAc 0 0.71 a. F.R. bicyclic Chem 3, 140(1971) The Me substituent appears to respond strictly to the decrease in nonbonding interactions L. A. Freiberg, J. Org. Chem 31, 804(1966) in axial conformer. With the more polar substituents, electrostatic effects due to the rigonal ring carbon offset the decreased steric environment. J. Org. Chem. 43.R H C H H Me H Me H R H C C Me H H H H H C Me Me Me H H H H H R H H Me H H Si Me Me Me H H R H Me Me H Sn Me Me Me H Me Me Me H Monosubstituted Cyclohexanes: A Values Keq DG° = –RTlnKeq ■ The A– Value, or -DG°, is the preference of the substituent for the equatorial position. ■ Me - axial has 2 gauche butane interactions more than Me-equatorial. Expected destabilization: » 2(0.88) kcal/mol = ~1.8 kcal/mol; Observed: 1.74 kcal/mol A Values depend on the relative size of the particular substituent. 1.74 1.80 2.15 5.0 Evans, Breit Conformational Analysis: Cyclic Systems-4 Chem 206 A–Value The "relative size" of a substituent and the associated A-value may not correlate. For example, consider the –CMe 3 and –SiMe 3 substituents. While the –SiMe 3 substituent has a larger covalent radius, is has a smaller A-value: A–Value 4.5-5.0 2.5 1.1 Can you explain these observations? ■ The impact of double bonds on A-values: Lambert, Accts. Chem. Res. 1987, 20, 454 R = Me substituent A-value (cyclohexane) 0.8 1.74 R = OMe 0.8 0.6 R = OAc 0.6 0.71 -DG° The Me substituent appears to respond strictly to the decrease in nonbonding interactions in axial conformer. With the more polar substituents, electrostatic effects due to the trigonal ring carbon offset the decreased steric environment