K.A. Beaver D. A. Evans Some Curtin-Hammett Examples Chem 206 Tropane alky lation is a well-known example Enantioselective lithiat less stable more stable S-BuLi (1-Sparteine faster"Me- Because sparteine is ()-Sparteine ave different minor product The less stable conformer reacts much faster than the more stable onformer, resulting in an unexpected major product Joc1974319 faster owe Oxidation of piperidines -. P2N、∠O less stable Me Me,c 只 Me more stable 82-87% slower:k1 H202 aste 0 her, reaction in the absence of ( -sparte minor produci Ratio: 5: 95 major product enantioselectivity is the same over the course of the reaction. If they were not uilibrating the enantioselectivity should be higher at lower conversions When the equilibrium constant is known, the Curtin-Hammett derivation This is a case of Dynamic Kinetic Resolution: Two enantiomeric alkyl be used to calculate the relative rates of reaction of the two lithium complexes are equilibrating during the course of a reaction with an conformers. Substituting the above data into[PBVPal= k2K/k,, the ratio Beak. Acc. Chem. Res. 1996. 552 Note that in this case, the more stable conformer is also the faster reacting conformer Tet1972573 Tet1977915N Me H Me3C O – Me3C H Me N N Me H Me3C N Me N Me N Me 13Me N Me 13Me + + + i-Pr2N O Me H i-Pr2N O Me Li•sparteine s-BuLi Me3C H Me N O – i-Pr2N O Me Cl H2O2 i-Pr2N O Me Li i-Pr2N O Me i-Pr2N O Me Li•sparteine N N K. A. Beaver, D. A. Evans Some Curtin-Hammett Examples Chem 206 k1 k2 Keq = 10.5 Ratio: 5 : 95 + less stable more stable slower faster minor product major product Oxidation of piperidines: major product minor product 13 Me–I 13 Me–I slower faster less stable more stable Tropane alkylation is a well-known example. When the equilibrium constant is known, the Curtin-Hammett derivation can be used to calculate the relative rates of reaction of the two conformers. Substituting the above data into [PB]/[PA] = k2K/k1, the ratio k2/k1 ~ 2. Note that in this case, the more stable conformer is also the faster reacting conformer! The less stable conformer reacts much faster than the more stable conformer, resulting in an unexpected major product! JOC 1974 319 Tet. 1972 573 Tet. 1977 915 (-)-Sparteine slower faster 82 - 87% ee This is a case of Dynamic Kinetic Resolution: Two enantiomeric alkyl lithium complexes are equilibrating during the course of a reaction with an electrophile. Beak, Acc. Chem. Res, 1996, 552 Enantioselective Lithiation: (-)-Sparteine Enantioselectivities are the same, regardless of whether or not the starting material is chiral, even at low temperatures. Further, reaction in the absence of (-)-sparteine results in racemic product. Note that the two alkyllithium complexes MUST be in equilibrium, as the enantioselectivity is the same over the course of the reaction. If they were not equilibrating, the enantioselectivity should be higher at lower conversions. Because sparteine is chiral, these two complexes are diastereomeric and have different properties