D. A. Evans. M. Dart Epoxides as electrophiles Chem 206 STERIC ELECTRON/C AND CONFORMATIONAL EFFECTS IN EPOXIDE/NUCLEOPHILE REACTIONS REGIOSELECTIVITY OF EPOXIDE RING OPENING NEUTRAL OR BASIC CONDIT/ONS: SN2 arkerRE. Isaacs, N. c. Chem. rev. 1959. 59. 737-799. Rosowsky, A. In The Chemistry of Heterocyclic Compounds Weissberger, A, Ed; Interscience: New York, 1964: Vol 19, Part 1, p 1. H SN2 Transition-State Buchanon, J. G: Sable, H. Z. In Selective Organic Transformations: Thyagarajan, B S Ed. Wiley: New York, 1972: VoL. 2, p 1 Berti, G. In Topics in Stereochemistry, Allinger, N. L. Eliel, E L, Eds. Interscience Publishers: New York, 973: Vol. 7, p93 rnha R=various alkyl, aryl, or vinyl substituents Rao,A.S:Paknikar,SK;Kirtane,JG.Tetrahedron1983,39,2323 R2NH Sharpless, B K, Behrens, C. H. Katsuki, T Lee, A. W. M; Martin, V.S.; Takatani, M Viti, S. M: Walker, F. J; Woodward, S.S. Pure Appl. Chem. 1983, 55, 589-604 Behrens, C H;, Sharpless, B. K. Aldrichimica Acta 1983, 16, 67-80 Due to ring strain, bond breaking is more advanced than bond making in the transition-state relative to a normal SN2 reaction. In addition, the carbon atom Gorzynski Smith, J. Synthesis 1984, 629-656 at which displacement takes place will bear a partial positive charge in the ewars,E.G. In Comprehensive Heterocyclic Chemistry, Katritzky, A.R., Ed; transition-state Normal" SN2 behavior is observed under neutral or basic conditions to provide Rossiter, B E. In Assymetric Synthesis; Morison, J D, Ed. Academic: New York, Ris alkyl or a group having no marked inductive or conjugative effects 1985: Vol 5, Chapter 7. Hanson, R. M. Chem Rev. 1991, 91, 437-475 Exceptions: Hydrogenation in the presence of Raney-nickel proceeds with Also see: Larock, R. C. Comprehensive Organic Transformations, p 505-526 opposite regioselection Parker,RE:Isaacs,NC.Chem.Rev.1959,59,737-799.O R' H Nu H H O R' R' Nu OH D. A. Evans, M. Dart Epoxides as Electrophiles Chem 206 Parker, R. E.; Isaacs, N. C. Chem. Rev. 1959, 59, 737-799. Rosowsky, A. In The Chemistry of Heterocyclic Compounds; Weissberger, A., Ed.; Interscience: New York,1964: Vol 19, Part 1, p 1. Buchanon, J. G.; Sable, H. Z. In Selective Organic Transformations; Thyagarajan, B. S., Ed.; Wiley: New York,1972: Vol. 2, p 1. Berti, G. In Topics in Stereochemistry; Allinger, N. L. ; Eliel, E. L., Eds.; Interscience Publishers: New York, 973: Vol. 7, p 93. Rao, A. S.; Paknikar, S. K.; Kirtane, J. G. Tetrahedron 1983, 39, 2323. Sharpless, B. K.; Behrens, C. H.; Katsuki, T.; Lee, A. W. M.; Martin, V. S.; Takatani, M.; Viti, S. M.; Walker, F. J.; Woodward, S. S. Pure Appl. Chem. 1983, 55, 589-604. Behrens, C. H.; Sharpless, B. K. Aldrichimica Acta 1983, 16, 67-80. Gorzynski Smith, J.; Synthesis 1984, 629-656. Lewars, E. G. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Ed.; Pergamon Press: New York,1984: Vol. 7, p 100. Weissberger, A.; Taylor, E.C. In The Chemistry of Heterocyclic Compounds; Hassner A., Ed.; Wiley: New York, 1985: Vol. 42, Part 3, p 1. Rossiter, B. E. In Assymetric Synthesis; Morrison, J. D., Ed.; Academic: New York, 1985; Vol. 5, Chapter 7. Hanson, R. M. Chem Rev. 1991, 91, 437-475. Also see: Larock, R. C. Comprehensive Organic Transformations, p 505-526. STERIC, ELECTRONIC, AND CONFORMATIONAL EFFECTS IN EPOXIDE / NUCLEOPHILE REACTIONS Reviews Parker, R. E.; Isaacs, N. C. Chem. Rev. 1959, 59, 737-799. R = various alkyl, aryl, or vinyl substituents SN2 Transition-State Due to ring strain, bond breaking is more advanced than bond making in the transition-state relative to a normal SN2 reaction. In addition, the carbon atom at which displacement takes place will bear a partial positive charge in the transition-state. "Normal" SN2 behavior is observed under neutral or basic conditions to provide nucleophilic attack at the least substituted carbon with inversion. R' is alkyl or a group having no marked inductive or conjugative effects. Exceptions: Hydrogenation in the presence of Raney-nickel proceeds with opposite regioselection. d - d - d + H - N3 - RO￾RS￾RNH2 R2NH NH3 R - Nu = Nu REGIOSELECTIVITY OF EPOXIDE RING OPENING NEUTRAL OR BASIC CONDITIONS: SN2 ‡