Synthesis of Multisubstituted Guanidines through Palladium-Catalyzed Insertion of Isonitriles

Pei-Xia Li; Xiu-Jin Meng; Li Yang; Hai-Tao Tang; Ying-Ming Pan

doi:10.1055/s-0037-1610981

Synlett, Table of Contents

Synlett 2018; 29(17): 2326-2330
DOI: 10.1055/s-0037-1610981

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Synthesis of Multisubstituted Guanidines through Palladium-Catalyzed Insertion of Isonitriles

Pei-Xia Li

^aState Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, P. R. of China Email: httang@gxnu.edu.cn

,

Xiu-Jin Meng

^aState Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, P. R. of China Email: httang@gxnu.edu.cn

,

Li Yang*

^bGuangxi Key Laboratory of Special Non-wood Forest Cultivation and Utilization, Guangxi Zhuang Autonomous Region Forestry Research Institute, Nanning, 530002, P. R. of China Email: yangli2828@yeah.net

,

Hai-Tao Tang*

^aState Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, P. R. of China Email: httang@gxnu.edu.cn

,

Ying-Ming Pan

^aState Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, P. R. of China Email: httang@gxnu.edu.cn

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Abstract

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Abstract

A new method for the synthesis of multisubstituted guanidines through tandem intermolecular insertion of isonitriles with unactivated amides has been developed. In this study, isonitriles could be used not only as reaction materials but also as the source of amines.

Key words

insertion of isonitriles - unactivated amides - cascade transformation - palladium

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References

References and Notes

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13 Typical Procedure: To a round-bottom flask was added amide 1 (0.3 mmol), tert-butyl isocyanide 2 (0.72 mmol), PdCl₂, and Cs₂CO₃, and MeCN (2.0 mL) was added under air. The reaction mixture was stirred at 70 °C for ca. 2 h, and the progress of the reaction was monitored by TLC. The reaction mixture was evacuated under vacuum, and the residue was further purified by silica gel column chromatography (petroleum ether and ethyl acetate) to afford the product 3.

14a Representative Analytical Data for 3b: White solid; mp 137–139 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.94 (d, J = 7.4 Hz, 1 H), 7.25–7.14 (m, 3 H), 2.63 (s, 3 H), 1.46 (s, 18 H). ¹³C NMR (100 MHz, CDCl₃): δ = 179.55 (s), 158.43 (s), 139.81 (s), 137.54 (s), 130.84 (s), 129.46 (s), 128.83 (s), 124.86 (s), 50.92 (s), 29.87 (s), 21.39 (s). HRMS (ESI): m/z [M+H]⁺ calcd for C₁₇H₂₈N₃O: 290.2227; found: 290.2215.

Supplementary Material

Supporting Information