Sarah siska. C. A. Morales Correlating Theory with Experiment-Peter Wipf-1 Chem 206 4,4-Disubstituted Cyclohexadienones: Experimental Data Wipf Seeking an Explanation A Stereoelectronic effect? MeMaB OR、THF Neither vinylogous Felkin nor vinylogous Cieplak sufficiently explains or predicts selectivity 78°CMe HO R Vinylogous Felkin-Anh") KEY:a:βed) vinylogous Anh-Eisenstein"model" vinylogous Cieplak"model LUMO of enone has phase inversion due to double bond stabilizing a of the incipient bond between carbonyl and donorlacceptor orbital correlation between ratio of isomers 79:1(26%) 48:1(81%) 86:1(32%) stabilizing homo of nucleophile predicts B attack-wrong product ng of the b face is OTMS ce 1.4-addition, when Electrostatic effect? Substrate with inverted dipole exhibits good B selectivity! 55:1(53%) 77:1(93%) 82:1(85% OMe CF2 CF3 1 CF2CF3 solvent OMe Wipf, P. Kim, Y.J. Am. Chem. Soc. 1994, 116,11678 32:1(79 11:1(29%) Wipf, P. Jung, J-K. Chem. Rev. 1999, 99, 1469Sarah Siska, C. A. Morales Correlating Theory with Experiment-Peter Wipf-1 Chem 206 Me OMe O O O Me OTMS O Me OBz O O O O O O O O O Me OH O ' (58%) ' (39%) ' (42%) R' OR O R' HO OR Me R' Me OR HO MeMgBr THF -78 °C + 4,4-Disubstituted Cyclohexadienones: Experimental Data 7.9 : 1 (26%) 4.8 : 1 (81%) 8.6 : 1 (32%) 5.5 : 1 (53%) 17.7 : 1 (93%) KEY: : (yield) 8.2 : 1 (85%) 32 : 1 (79%) 11 : 1 (29%) ~4 Å ("vinylogous Felkin-Anh") CF2CF3 OMe O R' OR O M O Me OMe O Me OMe Nu b a b a Nu CF2CF3 HO OMe Me CF2CF3 Me OMe HO Nu-M solvent + 1 5 : Wipf Seeking an Explanation "vinylogous Anh-Eisenstein" model "vinylogous Cieplak" model • stabilizing s* of the incipient bond • predicts a attack, but no qualitative correlation between ratio of isomers and s energy of donor C–C bonds LUMO of enone has phase inversion due to double bond between carbonyl and donor/acceptor orbital Stereoelectronic effect? Chelate shielding of the b face is not likely, since 1,4-addition, when it does occur, is b-selective. Electrostatic effect? Substrate with inverted dipole exhibits good b selectivity! Neither vinylogous Felkin nor vinylogous Cieplak sufficiently explains or predicts selectivity. • stabilizing HOMO of nucleophile • predicts b attack -- wrong product! Wipf, P.; Kim, Y. J. Am. Chem. Soc. 1994, 116, 11678 Wipf, P.; Jung, J-K. Chem. Rev. 1999, 99, 1469