Sarah Siska, C A Morales Correlating Theory with Experiment-Peter Wipf-2 Chem 206 Quantitative Correlation Between Facial Selectivity An Electrostatic Take on Some Controversial Cases and Dipole Moment (Felkin-Anh) Qualitative Assessment H p-PhNO 2 NaBH CO Me OMe 43:57 A Cheung, et al. J. Am. Chem. Soc. 1986, 108, 1598 86:1(32% 4.8:1(81%) [P"(42%) create too electrostatic much Dipole Moment Calculations interaction EWG Adcock, W; Cotton, J. Trout, N A. J. Org. Chem. 1994, 59, 1867 M (Felkin-Anh) Nu、OH Nu-M CO2 Me CO2 Me CO2 Me CF2CF3 c NaBH4 calculated dipole moments of five representative dienones using SPARTAN 6 linear correlation between pe ular vector of dipole moment and natural favorable log of facial selectivity electrostatic Mehta, G. Khan, FA J Am. Chem. S, 1990, interaction 112,6140 Paddon-Row, M N; Wu, Y-D: Houk, K N.J. ralidity of ground-state dipole moment: complexed carbonyl should affect dipoles of all dienone substrates in same manner Am.chem.Soc.1992,114,10638 Mehta, G.J. Org. Chem. 1993, 58, 1734 approach of nucleophile toward positive end of dipole favored-3 -2 -1 0 1 2 3 4 -3 -2 -1 0 1 2 3 4 calc. dipole moment [Debye] ln Sarah Siska, C. A. Morales Correlating Theory with Experiment-Peter Wipf-2 Chem 206 O O O O O Me OMe O CF2CF3 OMe O O O Me OMe O O [ ' (42%)] 32 : 1 (79%) 8.6 : 1 (32%) 4.8 : 1 (81%) Quantitative Correlation Between Facial Selectivity and Dipole Moment Qualitative Assessment • calculated dipole moments of five representative dienones using SPARTAN • linear correlation between perpendicular vector of dipole moment and natural log of facial selectivity • validity of ground-state dipole moment: complexed carbonyl should affect dipoles of all dienone substrates in same manner • approach of nucleophile toward positive end of dipole favored Dipole Moment Calculations CO2Me O CO2Me O EWG O OH CO2Me CO2Me HO Nu O O O R R CO2Me CO2Me Nu OH anti d + Nu: d – syn anti d + Nu: d – d – syn Nu d – d + d – d – d + d + d + anti syn O X NaBH4 Nu-M NaBH4 MeLi A X HO H C D X H OH B p-PhNO2 F CO2Me CF3 SiMe3 OH X An Electrostatic Take on Some Controversial Cases anti syn Cheung, et al. J. Am. Chem. Soc. 1986, 108, 1598 A : B + 66 : 34 62 : 38 61 : 39 59 : 41 45 : 55 43 : 57 favorable electrostatic interaction hydroxyl may create too much lone-pair repulsion (Felkin-Anh) Adcock, W.; Cotton, J.; Trout, N. A. J. Org. Chem. 1994, 59, 1867 (Felkin-Anh) + Nu-M 70 >90 30 10 : : : favorable electrostatic interaction Mehta, G.; Khan, F. A. J. Am. Chem. S, 1990, 112, 6140 Paddon-Row, M. N.; Wu, Y-D.; Houk, K. N. J. Am. Chem. Soc. 1992, 114, 10638 Ganguly, B.; Chandrasekhar, J.; Khan, F. A.; Mehta, G. J. Org. Chem. 1993, 58, 1734