Aza-Henry Reaction of Ketoimines Catalyzed by Na₂CO₃: An Efficient Way to β-Nitroamines

Abstract

A simple and efficient way to β-nitroamines via aza-Henry reaction of N-tosyl ketoimines and nitromethane has been developed. In the presence of only 5 mol% Na₂CO₃, most of the N-tosyl ketoimines can react to give products in good to excellent yields (up to 99%) in THF at room temperature.

Key words

aza-Henry reaction - inorganocatalyst - ketoimines - nitromethane - β-nitroamines

References and Notes

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13

To demonstrate that the size of R is important in terms of the reactivity, some other examples, such as phenyl ethyl ketimine, phenyl cyclic ketoimine, etc., were examined, but no corresponding product was obtained. Meanwhile, some other nitroalkanes, such as nitroethane and nitropropane, were also examined; unfortunately, no corresponding product was obtained by the present method.

14

General Procedure for aza-Henry Reaction of Ketoimines
To a solution of 1a (0.2 mmol, 54.7 mg) with powdered Na₂CO₃ (5 mol%, 1.1 mg) suspended in THF (0.29 mL) was added MeNO₂ (10 equiv, 0.11 mL) at r.t. and the mixture was kept stirring for 24 h. The crude product was purified by column chromatography on SiO₂ (PE-EtOAc, 5:1) to give the corresponding product 2a. By the general procedure, compound 2a was obtained as a white solid in 86% isolated yield. ^¹H NMR (400 MHz, CDCl₃): δ = 1.69 (s, 3 H), 2.42 (s, 3 H), 4.81 (d, J = 12.8 Hz, 1 H), 4.94 (d, J = 12.8 Hz, 1 H), 5.93 (s, 1 H), 7.22-7.33 (m, 7 H), 7.63 (d, J = 8.4 Hz, 2 H). ^¹³ C NMR (100 MHz, CDCl₃): δ = 143.6, 139.7, 139.2, 129.6, 128.9, 128.4, 127.0, 125.3, 82.9, 60.1, 24.7, 21.5. ESI-HRMS: m/z calcd for C₁₆H₁₈N₂NaO₄S [M + Na]: 357.0879; found: 357.0882.