Evans. breit Conformational Analysis: Cyclic Systems-6 Chem 206 Let's now consider geminal substitution Let's now consider vicinal substitution Case 1: The prediction:△G°=A(Ph)-A(Me) △G°=+2.8-1.7=+1.1 kcal/ mol The prediction ob AG°=-0.32 kcal/mol △G°=+0.88-201.74)=+26 kcal/ mol predict neither ze this case Observed △G°=+2.74 kcal/mol Allinger, Tet. Lett. 1971, 3259 If the added gauche butane destabilization in the di-equatorial conformer had not been added the estimate would have been off Case 2. EMMe △G°=+2.8 AG°=-0.32 The conformer which places the isopropyl group equatorial is much more strongly preferred than would be suggested by A-Values. This is due to a syn pentane OH/Me interaction Problem: Can you rationalize the stereochemical outcome of this reaction? LiNR n-C4Hg' n-CAHg' diastereoselection 89: 11 Note the difference in the ph substituent in a& B D. Kim Co-workers. Tetrahedron Lett. 1986. 27. 943A Me Ph C B Me Ph D EtO O n-C4H9 H OH H Me Me H H Me Me H H LiNR2 MeI Me Me H H EtO Me O n-C4H9 H OH H Me Me H H Evans, Breit Conformational Analysis: Cyclic Systems-6 Chem 206 Let's now consider geminal substitution The prediction: DG° = A(Ph) – A(Me) DG° = +2.8 – 1.7 = +1.1 kcal/mol Observed: DG° = –0.32 kcal/mol Hence, when the two substituents are mutually interacting you can predict neither the magnitude or the direction of the equilibrium. Let's analyze this case. DG° = +2.8 DG° = –0.32 Allinger, Tet. Lett. 1971, 3259 The conformer which places the isopropyl group equatorial is much more strongly preferred than would be suggested by A- Values. This is due to a syn pentane OH/Me interaction. Let's now consider vicinal substitution The prediction: DG° = 1 gauche butane – 2A(Me) DG° = +0.88 – 2(1.74) = +2.6 kcal/mol Observed: DG° = +2.74 kcal/mol If the added gauche butane destabilization in the di-equatorial conformer had not been added, the estimate would have been off. Case 1: Case 2: D. Kim & Co-workers, Tetrahedron Lett. 1986, 27, 943. diastereoselection 89:11 Problem: Can you rationalize the stereochemical outcome of this reaction? Note the difference in the Ph substituent in A & B