Synlett 2018; 29(17): 2326-2330
DOI: 10.1055/s-0037-1610981
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Multisubstituted Guanidines through Palladium-Catalyzed Insertion of Isonitriles

Pei-Xia Li
a   State 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
a   State 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*
b   Guangxi 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*
a   State 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
a   State 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
› Author Affiliations
We thank the National Natural Science Foundation of China (No. 21362002), Science and Technology Major Project of Guangxi (No. AA17204058-21) and State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Nos. CMEMR2017-A02 and CMEMR2017-A07) for financial support.
Further Information

Publication History

Received: 21 July 2018

Accepted after revision: 26 August 2018

Publication Date:
26 September 2018 (online)


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.

Supporting Information

 
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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.