Thieme Chemistry Journal Awardees - Where Are They Now? Aerobic Oxidative Coupling of Tertiary Amines with Silyl Enolates and Ketene Acetals

Abstract

Cyclic tertiary amines can be oxidatively coupled with a variety of silyl enol ethers or ketene acetals to furnish tertiary Mannich bases. The reactions are catalyzed by simple copper salts employing elemental oxygen as the oxidant.

Key words

amines - C-H bond functionalization - copper - oxidative cross-coupling - oxidations

References and Notes

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7

General Procedure for the Oxidative Coupling of Amines
To a solution of the appropriate amine (0.12 mmol, 1.0 equiv) in acetone or MeOH (1.0 mL), the TMS enol ether or silyl ketene acetal (0.30 mmol, 2.5 equiv) and CuCl₂˙2H₂O (2 mg, 10 mol%) were added, and the mixture was stirred under an atmosphere of oxygen (1 atm) at r.t. After full conversion was achieved, H₂O and CH₂Cl₂ were added and the mixture was extracted with additional CH₂Cl₂. The combined organic phases were dried over MgSO₄ and concentrated in vacuo. The crude residue was purified by flash column chromatography on silica gel (5-10% EtOAc-pentane), giving the product as a solid or oil.