D.A. Evans, M. Dart Epoxides as Electrophiles Chem 206 REGIOSELECTIVITY OF EPOXIDE RING OPENINGS REGIOSELECTIVITY OF EPOXIDE RING OPENINGS EFFECT OF CONJUGATING SUBSTITUENTS EFFECT OF CONJUGATING SUBSTITUENTS ubstituent(X) Rati 100:00 36:64 70:30 7624 MeOH, H2SO4 10:90 -OMe NaoMe -H 30:70 Nadph 24:76 Good I donors(OMe)can stabilize the incipient carbocation to offset steric HOPh, TSOH 06: 94 effects Methoxide, which is more nucleophilic than phenoxide, has increased The reaction of styrene oxide with nucleophiles is a balance between sensitivity to sterics and exibits more SN2 behavior with attack at C-B being somewhat favored relative to phenoxide Resonance stabilization favors attack at the a-carbon Steric effects direct attack to the B-carbon Lewars, E.G.: In"Comprehensive Heterocyclic Chemistry": Katritzky, A.R. Ed Under acidic conditions attack at the a-carbon becomes more favorable Olefinic and acetylenic substituents behave similarly Parker.RE. Isaacs. N c. Chem. Rev. 1959. 59. 737-799O OH Nu Nu OH O X Nu OH X OH Nu X NaOMe -H NaOPh -OMe -H -NO2 NaOPh HOPh NaN3 MeONa PhLi LiBH4 LiAlH4 30:70 Nu 100:0 76:24 36:64 substituent (X) Ratio Lewars, E. G.; In "Comprehensive Heterocyclic Chemistry"; Katritzky, A. R., Ed.; Good p donors (OMe) can stabilize the incipient carbocation to offset steric effects. Methoxide, which is more nucleophilic than phenoxide, has increased sensitivity to sterics and exibits more SN2 behavior with attack at C-b being somewhat favored relative to phenoxide. REGIOSELECTIVITY OF EPOXIDE RING OPENINGS EFFECT OF CONJUGATING SUBSTITUENTS Nu￾a b 24:76 12:88 HOPh, TsOH 06:94 00:100 MeOH, H2SO4 10:90 100: 00 70:30 74:26 Nucleophile Ratio 100: 00 Parker, R. E.; Isaacs, N. C. Chem. Rev. 1959, 59, 737-799. REGIOSELECTIVITY OF EPOXIDE RING OPENINGS EFFECT OF CONJUGATING SUBSTITUENTS Nu￾The reaction of styrene oxide with nucleophiles is a balance between resonance and steric effects: Resonance stabilization favors attack at the -carbon. Steric effects direct attack to the -carbon. Olefinic and acetylenic substituents behave similarly. Under acidic conditions attack at the a-carbon becomes more favorable. a b D. A. Evans, M. Dart Epoxides as Electrophiles Chem 206