D. A. Evans Enolates Metalloenamines: Introduction Chem 206 Important References Tautomers: Structural isomers generated as a consequence of the 1, 3-shift of a proton adjacent to a X=Y bond. for example cA时 Icture and Reactivity of Lithium Enolates. From Pinacolone to Selective lkylations of Peptides. Difficulties and Opportunities Afforded by Complex H Structures D Seebach Angew. Chem. Int Ed. Engl, 27, 1624(1983) Stereoselective Alkylation Reactions of Chiral Metal Enolates".D. A. Evans Asymmetric Synthesis, 3, 1(1984) Keto-Enol Tautomers: Tautomerism may be catalyzed by either acids Generation of Simple Enols in Solution". B. Capon, B.-Z.Guo, F C Kwok, A. K or bases Siddhanta, and C Zucco Acc. Chem. Res 21, 121 (1988) pKa and Keto-Enol Equilibrium Constant of Acetone in Aqueous Solution.Y. Chiang, A J. Kresge, and Y. S. Tang J. Am. Chem. Soc. 106, 460 (1984) base catalysis Enols Enolates are the most important nucleophiles in organic biological chemistry E+) Rb Ra Acidity of Keto and Enol Tautomers: Consider Acetone Enamines metalloenamines, their nitrogen counterparts, are H3C CH3 H a。O、分DK=822( measured Ra Rb pK =1916(calculated) 3C Kresge, JACS 1984, 106, 460 metalloenamineD. A. Evans Enolates & Metalloenamines: Introduction Chem 206 "Structure and Reactivity of Lithium Enolates. From Pinacolone to Selective C-Alkylations of Peptides. Difficulties and Opportunities Afforded by Complex Structures". D. Seebach Angew. Chem. Int. Ed. Engl., 27, 1624 (1983). "Stereoselective Alkylation Reactions of Chiral Metal Enolates". D. A. Evans Asymmetric Synthesis, 3, 1 (1984). "Generation of Simple Enols in Solution". B. Capon, B.-Z. Guo, F. C. Kwok, A. K. Siddhanta, and C. Zucco Acc. Chem. Res. 21, 121 (1988). "pKa and Keto-Enol Equilibrium Constant of Acetone in Aqueous Solution". Y. Chiang, A. J. Kresge, and Y. S. Tang J. Am. Chem. Soc. 106, 460 (1984). Important References Ra O Rb Ra OH Rb Ra O – Rb El(+) El(+) Ra O Rb El Enols & Enolates are the most important nucleophiles in organic & biological chemistry. H + base Ra N Rb El(+) El(+) H + base Enamines & metalloenamines, their nitrogen counterparts, are equally important. R Ra N Rb R M Ra N Rb R H Ra N Rb R El Tautomers: Structural isomers generated as a consequence of the 1,3-shift of a proton adjacent to a X=Y bond. for example: + H + pK = 19.16 (calculated) + H pK = 10.94 (measured) + pK = 8.22 (measured) Acidity of Keto and Enol Tautomers: Consider Acetone: + H + – H + – H + + H + Keto-Enol Tautomers: Tautomerism may be catalyzed by either acids or bases: acid catalysis: + base catalysis: R CH3 O O – R H H H R OH R OH R H H CH3 O H H Z O R CH3 X Y Z X Y H H C O H3C CH3 C OH H3C C H H C H H H3C C O – C H H H3C C OH H3C C CH3 O C O – H3C C H H Kresge, JACS 1984, 106, 460 On the origin of the acidity of enols: Wiberg, JACS 1996, 118, 8291-8299 enamine metalloenamine