D. A. Evans Enolate Alkylation: Unusual Cases Chem 206 Cases which do not appear to give the expected product based on sterically Expected Results: the analysis of steric effects \COmE LDA OMe BnBr 97% ds +-Bur COmE 8%ds COmE R= Me, Et, CO2Me ≥88:12 eebach. He/y. chim. Acta 1987. 70. 1194 Contrasteric relatives Seebach, Angew. Chem. Int Ed 1981, 20, 1030 Ladner, Angew. Chem. Int. Ed 1982, 21, 449 ■ However: Me(0、O2Me -Bu MeOD >95%ds COS-t-Bu Moc BnBr 60%ds acetone 95%ds Seebach. He/. Chim. Acta 1987. 70. 1194 HMe Me rati,80:20 OMe cO2Me70:30 The enolate(MM-2) >95:5 Here is another example of a contrasteric alkylation HO2C LDA, conditions Ladner,chem.Ber.1983.116,3413-3426. (+)-menthyl-O2C CO2R Those factors defining olefin face selection are currently being defined: Would you have predicted the outcome of the following conditions reaction? R-CI THF,23℃80:20 +H-menthol R-Br THF-HMPA 0298 >94:6 78+20°C CMe2 K Yamada, Organic Synthesis Past Present, and Future, p 52 Danishefsky J. Org. Chem. 1991, 56, 387Cases which do not appear to give the expected product based on the analysis of steric effects R Me CO2Me Me O O O O R C3H5 H CO2Me Me Me O N t-Bu O H OLi OMe O Me O CO2Me Me CO2Me Me Me H CO2Me O CO2Me O OH Me Me Me MeO2C Me O O O O MeMe H HO2C (+)-menthyl–O2C Me X HO2C Me CO2R CO2R Me HO2C OH Me CMe2 S-t-Bu OLi t-Bu O O O t-Bu O OLi OMe Me Me OMe OLi t-Bu O O Me O OSiR3 R3SiO EtO Li R-Br R-Cl X THF-HMPA -78®-20 °C MeI MeI BnBr MeI BzCl HgI2 OSiR3 OSiR3 EtO2C Me Me O O t-Bu CO2Me Me Me CO2Me Me t-Bu O O R CO2Me O H N t-Bu O R O O t-Bu COS-t-Bu Here is another example of a contrasteric alkylation K. Yamada, Organic Synthesis Past Present, and Future, p 525 (+)-menthol 02:98 THF, 23 °C 80:20 conditions Ratio LDA, conditions ratio, 80 : 20 acetone LDA ■ However: Ladner, Angew. Chem. Int. Ed 1982, 21, 449 LDA R = Me, Et, CO2Me Seebach, Angew. Chem. Int. Ed 1981, 20, 1030 allyl-Br 88 : 12 D. A. Evans Enolate Alkylation: Unusual Cases Chem 206 The enolate (MM-2) Ladner, Chem. Ber. 1983, 116, 3413-3426. Seebach, Helv. Chim. Acta 1987, 70, 1194. Seebach, Helv. Chim. Acta 1987, 70, 1194. >95 : 5 70 : 30 >95%ds 60% ds 95%ds MeOD BnBr acetone 97% ds >98% ds >95% ds Sterically Expected Results: Contrasteric relatives: Danishefsky J. Org. Chem. 1991, 56, 387 >94 : 6 Those factors defining olefin face selection are currently being defined: Would you have predicted the outcome of the following reaction?