D.A. Evan Enolization with metal amides bases Chem 206 Base Structure Corey&Co-workers, Tetrahedron Lett.1984,25,491,495 Regioselective Enolization LiNR2 M-base THF,-78°c B (E)Geometry (4) Geometry Base temp control Ratio(A: B) LiN(-Pr)2 LDA)77:23 N(SiMe3)2-78 kinetic 955 Phc- kinetic 90:10 MeLi Me Ph3C-Li thermo LTMP)86:14 1090 Na-H thermo 26:74 thermo 38 A: Alkyl groups stabilize metal enolate Lithium Halide Effects Collum(J Am. Chem. Soc. 1991, 113, 9572) A: as m-o bond becomes more ionic a is attenuated Collum(J. Am. Chem. Soc. 1991, 113, 9575) Kinetic Selection sensitive to structure Collum(J Am. Chem. Soc. 1991, 113, 5053 LiNR M-base THF,78°C Ratio, (E): 2 ato:99:1 2Ph (25 LITMP 10% B pKeq est: 7(10") Unsaturated Ketones For the latest in the series of Column papers see: JACS 2000, 122, 2452-2458 N(i-Pr) kinetic enolate thermodynamic eno ee kinetic acidity handout for an extensive compilation of casesEt Me O LiNR2 O Me Et N Li Me Me Me Me LiNR2 Li–N(i-Pr)2 OLi Et Me Me Et OLi LiTMP Me Me Me Me Me3C Me N Li Et Me OLi OLi Me Et KO Me O Ph K–H Na–H O Me Ph3C–Li Ph3C–Li LiN(i-Pr)2 LiN(SiMe3 )2 t-BuOH O Ph O Me A A A OLi Ph OLi Me LiN(i-Pr)2 B B B OLi Ph OLi Me LiO Me D. A. Evans Chem 206 Ratio, (E):(Z) LiTMP, 10% LiBr 98 : 2 86 : 14 THF, -78 °C + Collum (J. Am. Chem. Soc. 1991, 113, 5053) Collum (J. Am. Chem. Soc. 1991, 113, 9575) Lithium Halide Effects Collum (J. Am. Chem. Soc. 1991, 113, 9572) (LiTMP) 86 : 14 (LOBA) 98 : 2 (LDA) 77 : 23 (E) Geometry (Z) Geometry + Base Structure Corey & Co-workers, Tetrahedron Lett. 1984, 25, 491, 495 THF, -78 °C M–base + Base temp control Ratio (A:B) –78 ° kinetic 99:1 –78 ° kinetic 95:5 –78 ° kinetic 90:10 heat thermo 10:90 heat thermo 26:74 heat thermo 38:62 Regioselective Enolization A: Alkyl groups stabilize metal enolate A: As M–O bond becomes more ionic A is attenuated M–base + Kinetic Selection sensitive to structure ratio: 99:1 estimated pKa's (Bordwell) (25) (18) Unsaturated Ketones kinetic enolate KOt–Bu thermodynamic enolate see kinetic acidity handout for an extensive compilation of cases. Enolization with Metal Amides bases pKeq est: 7 (10+7) For the latest in the series of Column papers see: JACS 2000, 122, 2452-2458