D.A. Evans Carbonyl Addition Reactions: Chelate Organization Chem 206 Kinetic Evidence for Chelate- Controlled C=o Additon Alpha-Versus Beta-Chelation Since o-m much more reactive than MgB Substrates which can participate in C=o chelation will be more reactive Chelate model since the effective ntration of chelated intermediate will be higher OCH2OBn R W. C. Still Co-workers Tetrahedron Lett. 1980. 21. 1031 Ketone + R-M R R-M OMg 78°C rel rate o Chelate Model -Bn 74 M. T Reetz Co-workers OMg) JAm.Chem.Soc.1983,105,4833 Me-MgCI THF 40: 60 -SiMe3 Other nu reported Me-TICI eference rxn -Si-H-P 1 rxn run inThE at-78° Eliel, Frye, JACS 1992, 114, 1778-84(read SiMe3 Me However, these trends are not transmitted strongly to B-chelation t isomer Bno Acid-78° Chelate Model M. T Reetz Co-workers 2.5 Tetrahedron Lett. 1984. 25. 729 95:5 OS(Pn)3 k? BF3-OEt2 R Note that beta chelation can be developed as a control element by R、M varying solvent&Nu Hence, organization a Note BF3 gives"apparent" chelate controlO Bu Me Me OR O Me2Mg O R M R Me2Mg R–M Me Me Bu OMgX OMgX OR Me Me R O M R R–M R –CMe3 –SiMe3 –Si-i-Pr3 R R O O H BnO Me OCH2OBn TBSO O Me O H BnO Me SiMe3 R-M Me MgBr Me Me OMgX OR O Me OBn OSi(i Me Pr)3 O R O O R R M R R O O R M Me2Mg Me2Mg CH2Cl2 Me-MgCl Me-TiCl3 R-M BnO OH Me R BnO OH Me SnCl4 TiCl4 BF3-OEt2 Me OH TBSO OCH2OBn Me THF CH2Cl2 Hence, organization better than through However, these trends are not transmitted strongly to b-chelation = 2.5 k2 k1 k2 k1 rxn run inTHF at - 78°C Eliel, Frye, JACS 1992, 114, 1778-84 (read) 1 7 9 –Bn 174 –Me 213 k1 k2 reference rxn rel rate product + Ketone + Substrates which can participate in C=O chelation will be more reactive since the effective concentration of chelated intermediate will be higher. Since much more reactive than Kinetic Evidence for Chelate-Controlled C=O Additon D. A. Evans Carbonyl Addition Reactions: Chelate Organization Chem 206 Alpha–Versus Beta-Chelation Chelate Model W. C. Still & Co-workers, Tetrahedron Lett. 1980, 21, 1031 diastereoselection 50 : 1 -78 °C + isomer M. T. Reetz & Co-workers J. Am. Chem. Soc.. 1983, 105, 4833. Solv. Ratio 40 : 60 90 : 10 Other nucleophiles reported Chelate Model 95 : 5 95 : 5 Acid Ratio Chelate Model M. T. Reetz & Co-workers Tetrahedron Lett. 1984, 25, 729. + isomer Acid -78 °C 85 : 15 ■ Note that beta chelation can be developed as a control element by varying solvent & Nu. ■ Note BF3 gives "apparent" chelate control