D. A. Evans Sharpless Epoxidation(V+5) Chem 206 The Sharpless Epoxidation I The literature precedent: Sheng, Zajecek, J. Org. Chem. 1970, 35, 1839 少TBFP VO(acac)2 -ROH ROOH I Next step: Sharpless, Michaelson JACS 1973, 95, 6136 VO(acac)2 80°c Aldrichimica Acta, 12, 63 (1979) Mo(CO)6 0-C2-C3C4=41° The Sharpless estimate: -50% Relative Rates(Diastereoselectivities) for the Epoxidation of Cyclohexene Derivatives JACS 1973, 95, 6136 t-BuOOH Substrate peracid Mo(CO)6 VO(acac)2 10 055(92:8)45(98:2)>20098:2) tBu Chem 3D Transition State 042(60:40)110(98:2)10.0(98:2) a. b The relative rate data apply only to a given column Values in parenthesis refer to the ratio of syn anti epoxide4 3 2 1 Relative Rates (Diastereoselectivities) for the Epoxidation of Cyclohexene Derivatives JACS 1973, 95, 6136 OH O O Me OH Me Me OH O Mo(CO)6 TBHP OH ROOH O V OR O O RO O O V OR O-OtBu O HO V O O O O RO tBu O HO OH Me Me Me OH OAc OH OH OH O Mo(CO)6 Mo(CO)6 t-BuOH RDS HO O tBu V RO O O O O OR V RO O OR O O V RO O HO R –ROH HO O O V O RO OR a,b The relative rate data apply only to a given column. Values in parenthesis refer to the ratio of syn:anti epoxide. krel a,b (diastereoselectivityc ) 11.0 (98 : 2) 10.0 (98 : 2) 0.07 (40 : 60) -- 4.5 (98 : 2) >200 (98 : 2) 1.00 1.00 0.42 (60 : 40) 0.046 (37 : 63) 0.55 (92 : 8) 1.00 Substrate VO(acac) peracid 2 80 °C Stereoselection 98:2 TBHP (90 % yield) ■ Next step: Sharpless, Michaelson JACS 1973, 95, 6136 Regioselection 20:1 80 °C TBHP VO(acac)2 ■ The literature precedent: Sheng, Zajecek, J. Org. Chem. 1970, 35, 1839 VO(acac)2 4 : 1 80 oC 1 : 1 Catalyst t-BuOOH slow Chem 3D Transition State Aldrichimica Acta, 12, 63 (1979) O–C2–C3–C4 = 41° The Sharpless estimate: ~50° The Sharpless Epoxidation + D. A. Evans Sharpless Epoxidation (V+5) Chem 206 ● ● ● ● ● ● ● ● ●