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Synlett 2020; 31(03): 280-284
DOI: 10.1055/s-0039-1691538
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Phenanthridinones by Palladium-Catalyzed Cyclization of N-Aryl-2-aminopyridines with 2-Iodobenzoic Acids in Water

Xiaojuan Ding
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu Rd S., Nanjing 211816, P. R. of China   Email: duanjd@njtech.edu.cn   Email: guok@njtech.edu.cn
,
Lei Zhang
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu Rd S., Nanjing 211816, P. R. of China   Email: duanjd@njtech.edu.cn   Email: guok@njtech.edu.cn
,
Yiyang Mao
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu Rd S., Nanjing 211816, P. R. of China   Email: duanjd@njtech.edu.cn   Email: guok@njtech.edu.cn
,
Binsen Rong
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu Rd S., Nanjing 211816, P. R. of China   Email: duanjd@njtech.edu.cn   Email: guok@njtech.edu.cn
,
Ning Zhu
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu Rd S., Nanjing 211816, P. R. of China   Email: duanjd@njtech.edu.cn   Email: guok@njtech.edu.cn
,
Jindian Duan∗
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu Rd S., Nanjing 211816, P. R. of China   Email: duanjd@njtech.edu.cn   Email: guok@njtech.edu.cn
,
Kai Guo  ∗
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu Rd S., Nanjing 211816, P. R. of China   Email: duanjd@njtech.edu.cn   Email: guok@njtech.edu.cn
b   State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, 30 Puzhu Rd S., Nanjing 211816, P. R. of China
› Author AffiliationsFinancial support for this study from the Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture (NO.XTE1826) and the Natural Science Research of Jiangsu Higher Education Institutions of China (19KJB150027) is gratefully acknowledged.
Further Information

Publication History

Received: 13 October 2019

Accepted after revision: 03 December 2019

Publication Date:
16 December 2019 (online)

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Abstract

The first Pd-catalyzed cyclization of N-aryl-2-aminopyridines with 2-iodobenzoic acids for the synthesis of phenanthridinones through C–H bond activation under very low catalyst loadings (down to 0.1 mol% Pd) in water is reported. This protocol features a broad substrate scope and provides easy efficient access to various phenanthridinones.

Key words

phenanthridinones - palladium catalysis - cyclization - arylaminopyridines - iodobenzoic acids

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1691538.
  • Supporting Information
 

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  • 16 Phenanthridinones 3; General Procedure Pd(OAc)2 (4.5 mg, 0.02 mmol) was dissolved in CH2Cl2 (1 mL) and 10 μL of the solution was added to a Schlenk tube equipped with a Teflon-coated magnetic stirrer bar. The solvent was then evaporated under high vacuum. The appropriate N-aryl-2-aminopyridine 1 (0.20 mmol), 2-iodobenzoic acid 2 (0.26 mmol), and Ag2O (32 mg, 0.14 mmol) were added to the Schlenk tube. Water (1.0 mL) was added, the tube was placed in a preheated oil bath (120 °C), and the mixture was stirred for 3 h. When the reaction was complete, the reaction tube was allowed to cool to r.t. and EtOAc was added. The organic layer was separated, and the aqueous layer was washed with EtOAc. The filtrate was concentrated under reduced pressure, and the crude product was purified by flash column chromatography (silica gel). 5-Pyridin-2-ylphenanthridin-6(5H)-one (3a) White solid; yield: 50 mg (93%); mp 185–186 °C. 1H NMR (400 MHz, CDCl3): δ = 8.77 (d, J = 4.1 Hz, 1 H), 8.53 (d, J = 7.9 Hz, 1 H), 8.27–8.22 (m, 2 H), 7.97–7.93 (m, 1 H), 7.76–7.73 (m, 1 H), 7.57–7.53 (m, 1 H), 7.46–7.42 (m, 2 H), 7.28–7.21 (m, 2 H), 6.51 (d, J = 8.4 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 161.7, 151.9, 150.6, 139.3, 138.2, 134.2, 133.0, 129.1, 128.8, 128.1, 125.7, 124.8, 124.1, 123.1, 122.9, 121.9, 118.9, 116.4. HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H13N2O: 273.1028; found: 273.1036.
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