D. A Evans. M. Dart Epoxides as Electrophiles Chem 206 GJOSELECTIVITY OF EPOXIDE RING OPENING ACIDIC CONDITIONS: BORDERLINE SN2 TO SN1 REGIOSELECTIVITY OF EPOXIDE RING OPENING ACIDIC CONDITIONS: BORDERLINE SN2 TO SN1 №u 70-85℃Me Normal prod Abnormal prod 56 HC,Et2O,△74 Disfavored sterically More"abnormal" is formed in H2o than in Et2o which is expected since the "Normal Product reaction proceeds through a polar transition state Major product usually Favored sterically The electron donating inductive effect of an extra methyl substituent slightly a In the borderline SN2 mechanisms overrides the additional steric effect thereby enhancing C-a attack HI, whose anion is most nucleophilic in the series of acids, provides the highest Nucleophilic attack occurs on the conjugate acid of the epoxide proportion of normal product as expected The transiton state is more polar and c-o bond cleavage is more advanced than in SN2 reactions Buchanon, J G: Sable, H. Z. In"Selective Organic Transformations Thyagarajan, B. S, Ed. Wiley: New York, 1972: VoL. 2, p 1 Epoxides which exhibit normal SN2 behavior under basic or neutral conditions give mixtures under acidic conditions Stewart, C A: VanderWerf, C. A. J Am. Chem. Soc. 1954, 76, 1259 Swain. C. G: Scott. C. B. J. Am. Chem. Soc. 1953. 75. 141 Steric factors are important although less so than observed in SN2 reactions The positive charge build up is stabilized by electron releasing groupsH H Nu H R H O R O H + R OH + OH R Nu R O H O H H R H Nu R O OH Nu R Nu R OH Me O OH X Me X Me OH O Me Me Me Cl OH Me Me OH Me Cl HI HBr HCl HX B A More "abnormal" is formed in H2O than in Et2O which is expected since the reaction proceeds through a polar transirtion state. The electron donating inductive effect of an extra methyl substituent slightly overrides the additional steric effect thereby enhancing C_a attack. HI, whose anion is most nucleophilic in the series of acids, provides the highest proportion of normal product as expected. HCl, Et2O, D 74 26 82 18 71 29 56 44 REGIOSELECTIVITY OF EPOXIDE RING OPENING ACIDIC CONDITIONS: BORDERLINE SN2 TO SN1 Normal Prod Abnormal Prod HX, H2O 70-85 °C HCl, H2O 45 55 a b a b Buchanon, J. G.; Sable, H. Z. In "Selective Organic Transformations"; Thyagarajan, B. S., Ed.; Wiley: New York, 1972: Vol. 2, p 1. Stewart, C. A.; VanderWerf, C. A. J. Am. Chem. Soc. 1954, 76, 1259. Swain, C. G.; Scott, C. B. J. Am. Chem. Soc. 1953, 75, 141. REGIOSELECTIVITY OF EPOXIDE RING OPENING Nucleophilic attack occurs on the conjugate acid of the epoxide. The transiton state is more polar and C_O bond cleavage is more advanced than in SN2 reactions. Epoxides which exhibit normal SN2 behavior under basic or neutral conditions give mixtures under acidic conditions. Steric factors are important although less so than observed in SN2 reactions. The positive charge build up is stabilized by electron releasing groups. ■ In the borderline SN2 mechanisms: "Normal Product" "Abnormal Product" "BORDERLINE" SN2 b a d + d - ++ ++ d - d + d + d + ACIDIC CONDITIONS: BORDERLINE SN2 TO SN1 b a SN1 SN1 Favored electronically Disfavored sterically Disfavored electronically Favored sterically R = alkyl Major product usually D. A. Evans, M. Dart Epoxides as Electrophiles Chem 206