D.A. Evans Carbonyl Addition Reactions: Chelate Organization Chem 206 Addition of Carbon Nucleopiles MgB TBs path A OCH2 OBn Chelate Model OCH2OBn OR diastereoselection 50: 1 Felkin: R=OR TBS Me-MgBr Chelate Model BSo path B W. C. Still Co-workers Tetrahedron Lett. 1980. 21. 1031 diastereoselection >100: 1 Chelation model RL IgEr path C M-O R Chelate only one isomer Y Kishi& Co-workers Chelate model Tetrahedron Lett. 1978. 19. 2745 SnB H Chelate Felkin: RL=OR nly one isomer Y Kishi Co-workers elate Mode (OR Tetrahedron lett 1978. 19. 2745 R=CH2OBn MgBr2 THF(O 20:80 R=CH20Bn MgBr2 CH2Cl2(-20)>99. R=CH2OBn TICl4 CH2Cl2(-78)>99: 1 MeMgBr R= SiMe2(tBu BF3-Et2O CH2Cl2(-78)5.95 G. Keck Co-workers. Tetrahedron Lett. 1984. 25. 265 Y Kishi Co-workers Chelate Model J.Am.Chem.Soc.1979,101,260H O OR R L H OR O SnBu3 RO H BF3-Et2O TiCl4 MgBr2 MgBr2 (OR) O C O M H R H C O O C H OR R L R L H H R L OR OH C6H11 H5C3 H5C3 C6H11 OH OR R L Nu OR OH OH OR Nu R L OH OR Nu R L O H O Me Et OBn H OCH2OBn TBSO O Me Me O O Me Et OBn H O TBSO OCH2OBn Me O O O Et H H H OMe Me Me Me R CH2OH H O THF Me MgBr Me-MgBr Me MgBr Et2O EtMgBr MeMgBr Me OH TBSO OCH2OBn Me Me OCH2OBn TBSO OH Me H OBn Et Me OH O Me Me O OH Me Et OBn H Et OH H R Et O R' Me Addition of Carbon Nucleopiles Chelation model ‡ path C path B path A ‡ Nu: ‡ Nu: D. A. Evans Carbonyl Addition Reactions: Chelate Organization Chem 206 Nu: Chelate Felkin: RL=OR G. Keck & Co-workers, Tetrahedron Lett. 1984, 25, 265 CH2Cl2 (-78°) 5 : 95 R = CH2OBn CH2Cl2 (-78°) >99 : 1 CH2Cl2 R = CH (-20°) 2OBn >99 : 1 20 : 80 Acid Solv. Ratio R = CH2OBn R = SiMe2(t)Bu THF (0°) Lewis Acid Felkin: RL=OR Chelate "only one isomer" Y. Kishi & Co-workers, J. Am. Chem. Soc. 1979, 101, 260. Y. Kishi & Co-workers, Tetrahedron Lett. 1978, 19, 2745 Chelate Model "only one isomer" "only one isomer" Y. Kishi & Co-workers, Tetrahedron Lett. 1978, 19, 2745 Chelate Model Chelate Model diastereoselection 50 : 1 diastereoselection >100 : 1 W. C. Still & Co-workers, Tetrahedron Lett. 1980, 21, 1031 Chelate Model Chelate Model