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C-Alkylation of enolates

9 real reactions from the literature, on six-membered cyclic ketones, 1,3-diketones and α,β-unsaturated ketones. Each scheme shows starting materials, conditions and products, with the yield and reference where the source reports them.

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  1. Enolate C-alkylation: cyclohexanone (a six-membered cyclic ketone) with 1) LDA / THF; 2) add; 3) NH4Cl workup gives 2-prop-2-ynylcyclohexan-1-one (the α-alkylated ketone). 45% yield.

  2. Enolate C-alkylation: a six-membered cyclic ketone with 1) LDA / THF; 2) MeI; 3) NH4Cl workup gives the α-alkylated ketone. 68% yield.

    Enolate C-alkylationTetrahedron 1998, 54, 2669
  3. Enolate C-alkylation: cyclohexanone (a six-membered cyclic ketone) with 3) NH4Cl workup; 2 eq. tBuOK; 2 eq. MeI gives 2,2-dimethylcyclohexan-1-one (the α-alkylated ketone). 49% yield.

    Enolate C-alkylationJ. Org. Chem. 2016, 81, 6686
  4. Enolate C-alkylation: 1,4-dibromobutane (a primary alkyl bromide) and cyclohexanone (a six-membered cyclic ketone) with tBuOK; PhMe gives spiro(4.5)decan-6-one (the α-alkylated ketone). 63% yield.

    Enolate C-alkylationOrg. Lett. 2007, 9, 3233
  5. Enolate C-alkylation: dimedone (a 1,3-diketone) with 1 eq.; + diMe etc gives the α-alkylated ketone. 15% yield.

    Enolate C-alkylationOrg. Lett. 2019, 21, 5172
  6. Enolate C-alkylation: 1,3-cyclohexanedione (a 1,3-diketone) with Et3N / DMSO gives 2-(2-oxopropyl)cyclohexane-1,3-dione (the α-alkylated ketone). 67% yield.

    Enolate C-alkylationEur. J. Org. Chem. 2016, 5169
  7. Enolate C-alkylation: an α,β-unsaturated ketone with 2 eq. tBuOK; 2 eq. MeI gives the α-alkylated ketone. 67% yield.

  8. Enolate C-alkylation: cyclohexanone (a six-membered cyclic ketone) with 1) LiN(SiMe3)2; 2) BF3 Et2O; 3) NH4Cl workup gives 2-(2-hydroxycyclopentyl)cyclohexan-1-one (the α-alkylated ketone). 52% yield.

    Enolate C-alkylationJ. Org. Chem. 2003, 68, 3049
  9. Enolate C-alkylation: cyclohexanone (a six-membered cyclic ketone) with 1) Na, NH3; CH3CH2OCH2CH3, Δ; NaBr gives 2-prop-2-enylcyclohexan-1-one (the α-alkylated ketone).