K. A Beaver, D. A. Evans Conformational Analysis and Reactivity: Curtin-Hammett Principle Chem 206 eading References: J. L Seeman, J. Chem. Ed 1986, 63, 42-48 Case 1: Kinetic Quench J I Seeman. Chem Rev. 1983. 83. 83-134 >>kA, kB: If the rates of rea rate of conversion, a and b cannot eq irse of the reaction, and the product distribution initia How does the conformation of a molecule effect its [PA (Alo Consider the following example Do the two different conformers react at the same rate or different rates? The situation In this case, the product distribution depends solely on the initial ratio of the two conformers Consider two interconverting conformers, A and B, each of which can undergo a reaction resulting in two different products, PA and PB hindrance PA B PB AG=-30 kcal/mol We'll consider two limiting cases Me-Br (1)The rate of reaction is faster than the rate of conformational interconversion (2 )The rate of reaction is slower than the rate of conformational interconversion major product minor product reactants are not in equilibrium during the course of the reaction and complex mathmatical solutions are necessary. See Seeman, Chem. Rev. 1983, 83-144 for While enolate conformers can be equilibrated at higher temperatures, the products of analytical solutions alkylation at C always reflect the initial ratio of enloate isomers Padwa. JACS 1997 4565J. I. Seeman, Chem Rev. 1983, 83, 83-134. J. I. Seeman, J. Chem. Ed. 1986, 63, 42-48. N Me N Me PA [PA] [PB] [B]o [A]o A B PB (1) kB k1 kA k2 PA O N Me Me H A Me–Br N O Me Me Me H B Me O N Me H N O Me Me H Me PB Me–Br K. A. Beaver, D. A. Evans Conformational Analysis and Reactivity: Curtin-Hammett Principle Chem 206 Leading References: How does the conformation of a molecule effect its reactivity? Consider the following example: Do the two different conformers react at the same rate, or different rates? What factors determine the product distribution? major minor Consider two interconverting conformers, A and B, each of which can undergo a reaction resulting in two different products, PA and PB. The situation: See also Eliel, pp. 647-655 13 Me–I 13 Me–I DG° DGAB ‡ DG1 ‡ DG2 ‡ Rxn. Coord. Energy k1 , k2 >> kA, kB: If the rates of reaction are faster than the rate of interconversion, A and B cannot equilibrate during the course of the reaction, and the product distribution (PB/PA) will reflect the initial composition. = In this case, the product distribution depends solely on the initial ratio of the two conformers. major product minor product less stable more stable Padwa, JACS 1997 4565 DG = -3.0 kcal/mol (ab initio calculations) Case 1: "Kinetic Quench" We'll consider two limiting cases: (1) The rate of reaction is faster than the rate of conformational interconversion (2) The rate of reaction is slower than the rate of conformational interconversion -78°C While enolate conformers can be equilibrated at higher temperatures, the products of alkylation at -78° C always reflect the initial ratio of enloate isomers. If the rates of conformationall interconversion and reaction are comparable, the reactants are not in equilibrium during the course of the reaction and complex mathmatical solutions are necessary. See Seeman, Chem. Rev. 1983, 83 - 144 for analytical solutions. steric hindrance