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

Yuzhu Yang; Ting Wu; Youlai Fang

doi:10.1055/s-0037-1609552

Synlett, Table of Contents

Synlett 2018; 29(14): 1909-1913
DOI: 10.1055/s-0037-1609552

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

Authors

Yuzhu Yang *

^aState 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

^bThe 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

^aState 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

^bThe 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

^aState 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

^bThe Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 3491 Baijin Road, Guiyang 550014, P. R. of China

Abstract

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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.

Key words

regioselective coupling - propargyl carbonate - C-3 benzylated indolizine - DBFphos - synthetic method

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References

References and Notes

1a Comprehensive Heterocyclic Chemistry: The Structure, Reactions, Synthesis, and Uses of Heterocyclic Compounds. Vol. 18. Katritzky AR. Rees CW. Pergamon Press; Oxford: 1984
1b Comprehensive Heterocyclic Chemistry II. Vol. 1-8. Katritzky AR. Rees CW. Scriven EF. V. Pergamon; Oxford, U. K.: 1996
1c Micheal JP. Alkaloids 2001; 55: 91
1d Micheal JP. Nat. Prod. Rep. 2002; 19: 742

2 Sharma P. Kumar A. Sharma S. Rane N. Bioorg. Med. Chem. Lett. 2005; 15: 937
3 James DA. Koya K. Li H. Liang GQ. Xia ZQ. Ying WW. Wu YM. Sun LJ. Bioorg. Med. Chem. Lett. 2008; 18: 1784
4 Teklu S. Gundersen L.-L. Riseand F. Tilset M. Tetrahedron 2005; 61: 4643
5 Facompre M. Tardy C. Bal-Mahieu C. Colson P. Perez C. Manzanares I. Cuevas C. Bailly C. Cancer Res. 2003; 63: 7392
6 Oslund RC. Cermak N. Gelb MH. J. Med. Chem. 2008; 51: 4708

For the indolizine synthesis from 1,3-dipolar cycloaddition approach, see:

7a Katritzky AR. Qiu G. Yang B. He H.-Y. J. Org. Chem. 1999; 64: 7618
7b Li F. Chen J. Hou Y. Li Y. Wu X.-Y. Tong X. Org. Lett. 2015; 17: 5376
7c Brioche J. Meyer C. Cossy C. J. Org. Lett. 2015; 17: 2800
7d Wang F. Shen Y. Hu H. Wang X. Wu H. Liu Y. J. Org. Chem. 2014; 79: 9556

For the indolizine synthesis from metal-catalyzed intramolecular cyclization approach, see:

8a Seregin IV. Gevorgyan V. J. Am. Chem. Soc. 2006; 128: 12050
8b Smith CR. Bunnelle EM. Rhodes AJ. Sarpong R. Org. Lett. 2007; 9: 1169
8c Zhang L. Li X. Liu Y. Zhang D. Chem. Commun. 2015; 51: 6633
8d Oh KH. Kim SM. Park SY. Park JK. Org. Lett. 2016; 18: 2204

For the indolizine synthesis from metal-catalyzed intermolecular cyclization approach, see:

9a Barluenga J. Lonzi G. Riesgo L. López LA. Tomás M. J. Am. Chem. Soc. 2010; 132: 13200
9b Helan V. Gulevich AV. Gevorgyan V. Chem. Sci. 2015; 6: 1928
9c Yang Y. Xie C. Xie Y. Zhang Y. Org. Lett. 2012; 14: 957

10 Wang X. Li S. Pan Y. Wang H. Liang H. Chen Z. Qin X. Org. Lett. 2014; 16: 580
11 Bonneau R. Romashin YN. Liu MT. H. Macpherson SE. J. Chem. Soc., Chem. Commun. 1994; 509
12 Wu T. Chen M. Yang Y. J. Org. Chem. 2017; 82: 11304
13 Guo L.-N. Duan X.-H. Liang Y.-M. Acc. Chem. Res. 2011; 44: 111

14a Tsuji J. Organic Syntheses with Palladium Compounds. Springer Verlag; Berlin: 1980: 37
14b Trost BM. Tetrahedron 1977; 33: 2615
14c Trost BM. Acc. Chem. Res. 1980; 13: 385
14d Trost BM. J. Organomet. Chem. 1986; 300: 263
14e Tsuji J. J. Organomet. Chem. 1986; 300: 281

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.

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