D. A. Evans. M. Dart Epoxides as electrophiles Chem 206 ACTIVATION OF 6-ENDO OVER 5-EXO EPOXIDE OPENINGS ALL YLIC EPOXIDE CYCLIZATION CIS-EPOXIDES OMe 0. 1 equiv CSA cH2C2,+40 t025°c 6-endo exo The olefinic substituent stabilize positve charge -CH=cHco, Me 86% up at C-a therefore the hexane is formed ￡CH=CHCI(E 762494% -CHCHCI 2 3367 -ccBr 87% The cis-epoxide stereochemistry disfavors highly selective 6-endo ring closure. This Stork claims that the axial orientation of the enolate has severe 1.3-diaxial interactions ay be due to failure of these substrates to attain a planar arrangement necessary for resembling those of a tert-butyl group. Therefore transition-state B, with the enolate in maximum orbital overlap and stabilization of the transition-state an equatorial position, is prefered and accounts for the stereoselectivity observed in the reactio OTBS 0.1 equv CSA 2LDA (92100% ."Tort 43%) 0. 1 equiv CSA Product Ratio Yield 0:100 Stork, G. Kobayashi, Y, Suzuki, T; Zhao, K. JACS 1990, 112, 1661-1663. 24:76 Stork, G: Zhoa, K. JACS 1990, 112, 5875-5876O Me O MeO - H H OMe O O - Me H H O HO R H H O HO R H O HO R MeO2C OTBS H H O O R HO HO R H H H H O O R O O H OH O O H H R O HO O H H H H R HO O OMe Me O HO Me O OMe Br O O OTBS O A B -CH=CH2 -CH=CHCO2Me -CCBr -CH=CHCO2Me -CH=CH2 favored 2 LDA a The olefinic substituent can stabilize positve charge build￾up at C- therefore the cyclo￾hexane is formed. ALLYLIC EPOXIDE CYCLIZATION Stork claims that the axial orientation of the enolate has severe 1,3-diaxial interactions resembling those of a tert-butyl group. Therefore transition-state B, with the enolate in an equatorial position, is preferred and accounts for the stereoselectivity observed in the reaction. -78 °C to rt (43 %) Stork, G.; Kobayashi, Y.; Suzuki, T.; Zhao, K. JACS 1990, 112, 1661-1663. Stork, G.; Zhoa, K. JACS 1990, 112, 5875-5876. 24:76 86% 0:100 81% Substrate (R) Product Ratio Yield 0:100 87% -CH=CHCl (Z) -CH=CHCl (E) Substrate (R) Product Ratio Yield 0:100 86% 44:56 95% 76:24 94% 33:67 92% 6-endo 5-exo (92-100 %) 0.1 equiv CSA CH2Cl2 , -40 to 25 °C 0.1 equiv CSA CH2Cl2 , -40 to 25 °C The cis-epoxide stereochemistry disfavors highly selective 6-endo ring closure. This may be due to failure of these substrates to attain a planar arrangement necessary for maximum orbital overlap and stabilization of the transition-state. CIS-EPOXIDES 0.1 equiv CSA CH2Cl2 , -40 to 25 °C ACTIVATION OF 6-ENDO OVER 5-EXO EPOXIDE OPENINGS D. A. Evans, M. Dart Epoxides as Electrophiles Chem 206