D.A. Evans Enols, Enolates, Enamines Metalloenamines: Reactivity Hierarchy Chem 206 ■ Metalloenamines Decreasing Nucleophilicity Imines may be transformed into their conjugate bases(enolate counterparts) with strong bases: Metal R pKa-2933 Li-NR R-MgX The usual bases employed are either mides(LDA) or Grignard eagents. Note that grignard reagents do not add to the c=n pi-bond due to H3O the reduced dipole. With this functional group, deprotonation is observed to be the preferred reaction I When to use a metalloenamine -C-Cl Metalloenam antly more nucleophilic than ketone or ald when less reactive electrophiles are R-C-H o Me C no reaction However: relationship Meta、R ood yie ./R-C-OR+ Metalloenamines are reactive enough to open epoxides in good yield Ketone enolates are only marginally reactive enough for this family of electrophiles Me2CH--I R-C Nature uses enamines. " stabilized"enolates, and enol derivatives in C-C bond constructions extensivelyX Decreasing Nucleophilicity Decreasing Electrophilicity C C OMe C C NR2 C C O C C NR N R R-MgX R C O Cl C H O R R C O R Me I C OR O R O H2C CH2 Me2CH I R C O NR2 O Me Me Me Me N R N OH R H3O + R O N Metal R N CH2 Li I Me Me Li-NR2 Li-NR2 OLi N Metal R N R N Me D. A. Evans Enols, Enolates, Enamines & Metalloenamines: Reactivity Hierarchy Chem 206 Nucleophile Electrophile Br2 , O3 + + + + + + + + + + + + + + + + + + + + + + – – ■ Metalloenamines: Imines may be transformed into their conjugate bases (enolate counterparts) with strong bases: The usual bases employed are either lithium amides (LDA) or Grignard reagents. Note that Grignard reagents do not add to the C=N pi-bond due to the reduced dipole. With this functional group, deprotonation is observed to be the preferred reaction. ■ When to use a metalloenamine: Metalloenamines are significantly more nucleophilic than ketone or aldehyde enolates. They are used when less reactive electrophiles are under consideration. For example: no reaction However: good yield Metalloenamines are reactive enough to open epoxides in good yield. Ketone enolates are only marginally reactive enough for this family of electrophiles. ■ Nature uses enamines, "stabilized" enolates, and enol derivatives in C–C bond constructions extensively. pKa~ 29-33 syn relationship