N-Heterocyclic Carbene Catalyzed Deuteration of Aldehydes in D₂O

Abstract

An N-heterocyclic carbene (NHC)-catalyzed direct deuteration of aldehydes in a mixed solvent of deuterium oxide (D₂O) and cyclopentyl methyl ether was established. The present deuteration is possibly initiated by the formation of a Breslow intermediate from the aldehyde and the NHC, with subsequent trapping by D₂O providing the monodeuterated aldehyde.

Key words

deuteration - aldehydes - N-heterocyclic carbenes - organocatalysis

• References and Notes

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For the physical and toxicological properties of CPME, see:
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• 14 Monodeuterated Aldehydes 1a-d ₁ to 1n-d ₁; General Procedure An 18 mL test tube was charged with the appropriate aldehyde (0.2 mmol), IMes·HCl (6.8 mg, 0.02 mmol), Na₂CO₃ (4.2 mg, 0.04 mmol), CPME (0.2 mL), and D₂O (1.0 mL). The tube was then sealed with a septum and the gas inside the tube was immediately replaced with Ar. The mixture was then heated at 120 °C for the appropriate time (Table 3), then extracted with EtOAc. The organic layers were dried (MgSO₄) and concentrated in vacuo. If necessary, the residue was purified by column chromatography (silica gel). 4-Methoxybenzaldehyde-d ₁ (1a-d ₁ ): Yield: 15.8 mg (58%; 99% D incorporation). ¹H NMR (400 MHz, CDCl₃): δ = 9.88 (s, 0.01 H), 7.84 (d, J = 8.2 Hz, 2 H), 7.00 (d, J = 8.2 Hz, 2 H), 3.89 (s, 3 H). ²H NMR (77 MHz, CHCl₃): δ = 9.91 (br s).
• 15 Because of the volatility of the aldehyde products, yields were determined by ¹H NMR with CH₂Br₂ as an internal standard, unless otherwise noted.