Synlett 2018; 29(14): 1909-1913
DOI: 10.1055/s-0037-1609552
letter
© Georg Thieme Verlag Stuttgart · New York

Palladium-Catalyzed Regioselective Coupling of Secondary Propargyl Carbonates and Ethyl 2-(pyridin-2-yl)acetate Derivatives: Facile Access to C-3 Benzylated Indolizines

a   State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, 3491 Baijin Road, Guiyang 550014, P. R. of China   Email: yangyuzhu15@126.com
b   The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 3491 Baijin Road, Guiyang 550014, P. R. of China
,
Ting Wu
a   State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, 3491 Baijin Road, Guiyang 550014, P. R. of China   Email: yangyuzhu15@126.com
b   The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 3491 Baijin Road, Guiyang 550014, P. R. of China
,
Youlai Fang
a   State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, 3491 Baijin Road, Guiyang 550014, P. R. of China   Email: yangyuzhu15@126.com
b   The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 3491 Baijin Road, Guiyang 550014, P. R. of China
› Author Affiliations
Financial support from the Natural Science Foundation of Guizhou Province (QKHJC[2017]1117, QKHJC[2018]1109, QKHPTRC[2017]5718, QKHTZ[2014]4007) and the West Light Foundation of The Chinese Academy of Sciences is acknowledged.
Further Information

Publication History

Received: 06 June 2018

Accepted after revision: 12 June 2018

Publication Date:
17 July 2018 (online)


Abstract

A palladium-catalyzed ligand controlled regioselective ­coupling reaction of secondary propargyl carbonates and ethyl 2-(pyridin-2-yl)acetate derivatives has been described, leading to C-3 benzyl­ated indolizines for the first time in moderate to good yields. DBFphos as the ligand is crucial to this high regioselective annulation reaction, and a plausible reaction mechanism has been proposed.

Supporting Information

 
  • References and Notes

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  • 15 General Procedure for the Synthesis of Indolizines from Propargyl Carbonates and Ethyl 2-(pyridin-2-yl)acetate Derivatives: Ethyl 2-(pyridin-2-yl)acetate (1a, 0.4 mmol), 1,3-diphenylprop-2-yn-1-yl methyl carbonate (2a, 0.2 mmol), Pd2(dba)3 (0.01 mmol), DBFphos (0.02 mmol), K2CO3 (0.4 mmol) were mixed under N2 atmosphere in DMF (2 mL). The reaction tube was heated in an oil bath at 120 °C for 16 h. After completion of the reaction, the reaction mixture was extracted with EtOAc (3 × 15 mL), and the solvent was removed under reduced pressure. The remaining crude product was then purified through column chromatography using silica gel (EtOAc–petroleum ether = 1:5) to afford 3a as a white solid in 65% yield. 1H NMR (500 MHz, CDCl3): δ = 8.24 (dd, J = 9.2, 1.3 Hz, 1 H), 7.53 (d, J = 7.0 Hz, 1 H), 7.23–7.32 (m, 5 H), 7.15 (t, J = 7.3 Hz, 2 H), 7.10 (t, J = 7.2 Hz, 1 H), 6.93– 6.99 (m, 3 H), 6.54 (td, J = 6.8, 1.3 Hz, 1 H), 4.11 (q, J = 7.1 Hz, 2 H), 4.08 (s, 2 H), 1.06 (t, J = 7.1 Hz, 3 H). 13C NMR (125 MHz, CDCl3): δ = 165.2, 137.5, 136.2, 135.4, 131.5, 130.5, 128.9, 127.8, 127.7, 127.1, 126.7, 123.4, 122.2, 121.4, 120.2, 112.6, 102.0, 59.3, 30.2, 14.3. HRMS (ESI): m/z [M + H]+ calcd for C24H22NO2 : 356.1645; found 356.1642.