Regioselective Synthesis of Unsymmetrical Vicinal Diamines via Azidoimination of Alkenes with TMSN₃ and Ketimines

Yongzhuo Xu, Boqiang Wang, Jiajia Wang*, Xuan Zhou, Jiaxing Chen, Xinjia Guo, Guo-Jun Deng*, Wen Shao*

*College of Chemistry, Xiangtan University, Xiangtan 411105, P. R, China, Email: gjdengxtu.edu.cn, shaowenxtu.edu.cn

Y. Xu, B. Wang, J. Wang, X. Zhou, J. Chen, X. Guo, G.-J. Deng, W. Shao, Org. Lett., 2023, 25, 8716-8721.

DOI: 10.1021/acs.orglett.3c03642

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Abstract

A highly regioselective intermolecular azidoamination of olefins under metal-free conditions enables an operationally simple synthesis of 2-azidoimines as versatile precursors to value-added vicinal unsymmetrical diamines. The approach proceeds through two differentiated N-centered radicals.

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proposed mechanism

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General Procedure

In the glove box, to a flame-dried 10 mL reaction tube were charged with 1 (0.2 mmol), 2 (54.4 mg, 0.3 mmol, 1.5 equiv), TMSN₃ (69.1 mg, 0.6 mmol, 3.0 equiv), DMAP (48.9 mg, 0.4 mmol, 2.0 equiv) and 1,4-dioxane (2.0 mL). Then PIFA (215.0 mg, 0.5 mmol, 2.5 equiv) was gradually added portion wise to the reaction mixture within 5 minutes under rapid stirring conditions. After stirred for another 5 minutes, the reaction mixture was filtered over a short pad of silica gel which was basified with triethylamine, washed with ethyl acetate and concentrated under vacuum to afford the crude mixture. The diastereoisomeric ratio was determined by ¹H NMR analysis of the crude reaction mixture.

Work-up method A

The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine = 99:1:1 to 10:1:0.1 as elution) to afford the pure product.

Work-up method B

In a 10 mL reaction tube, the crude mixture (from above) was dissolved in THF (1.0 mL), added a 20% citric acid solution (aq., 1.0 mL) at room temperature and the mixture was stirred for 2 hours. After being washed with EtOAc, the mixture was neutralized with solid NaHCO₃ and extracted with EtOAc (5 mL x 3). The combined extracts were dried over Na₂SO₄, then filtered and concentrated under vacuum to afford the crude primary amine product. The diastereoisomeric ratio was determined by ¹H NMR analysis of the crude reaction mixture. Then the residue was purified by silica gel flash column chromatography (typically using petroleum ether/ethyl acetate = 5:1 to 1:2 as elution) or prepared thin layer chromatography to afford the desired product

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Key Words

1,2-azidoamines, multicomponent reactions, PIFA

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ID: J54-Y2023