Synlett 2015; 26(10): 1391-1394
DOI: 10.1055/s-0034-1380694
letter
© Georg Thieme Verlag Stuttgart · New York

Highly Chemoselective and Regioselective Dehydrogenative Cross-Coupling Reaction between Pyridines and Ethers

Muhammad Salman
b  Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, P. R. of China
,
Xing-Fen Huang
b  Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, P. R. of China
,
Zhi-Zhen Huang*
b  Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, P. R. of China
a  Department of Chemistry, Zhejiang University, Xixi Campus, Hangzhou 310028, P. R. of China   Email: huangzhizhen@zju.edu.cn
› Author Affiliations
Further Information

Publication History

Received: 25 February 2015

Accepted after revision: 06 April 2015

Publication Date:
08 May 2015 (online)


Abstract

A highly chemoselective and regioselective dehydrogenative cross-coupling (DCC) reaction of unactivated pyridines with cyclic or acyclic ethers has been developed to give the corresponding 2- or 4-coupled pyridines in satisfactory yields. The DCC reaction affords an efficient and greener synthesis for a range of new pyridines. A possible mechanism involving radical substitution is also proposed.

Supporting Information

 
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  • 9 General Procedure of the DCC Reaction between Pyridine 1 and Ether 2 for the Synthesis of Monocoupled Pyridine 3 In a Teflon cap sealed tube, a mixture of Sc(OTf)3 (24.6 mg, 0.05 mmol), pyridine 1 (0.5 mmol), and DTBP (146 mg, 1.0 mmol, 2 equiv) in ether 2 (2 mL) was stirred at 140 °C for 8 h. Then the mixture was filtered, and the filtrate was concentrated under vacuum. The residue was purified by column chromatography (silica gel, PE–EtOAc as eluent) to give monocoupled pyridine 3. Characterization of Typical Monocoupled Pyridines 3 2-(1,4-Dioxan-2-yl)pyridine (3ab) Oil. 1H NMR (400 MHz, CDCl3): δ = 8.48 (d, J = 4.0 Hz, 1 H), 7.62 (t, J = 7.6 Hz, 1 H), 7.38 (d, J = 8.0 Hz, 1 H), 7.14 (t, J = 6.0 Hz,1 H), 4.67 (dd, J = 2.4, 10.0 Hz, 1 H), 4.07 (dd, J = 2.6, 11.4 Hz, 1 H), 3.92–3.84 (m, 2 H), 3.75–3.63 (m, 2 H), 3.45 (t, J = 10.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.9, 149.0, 136.6, 122.7, 120.7, 78.1, 71.2, 66.4, 66.3 ppm. HRMS (EI-TOF): m/z [M+] calcd for C9H11NO2: 165.0790; found: 165.0790. 2-(1,2-Dimethoxyethyl)pyridine (3af) Oil. 1H NMR (400 MHz, CDCl3): δ = 8.51 (d, J = 4.4 Hz, 1 H), 7.65 (t, J = 7.6 Hz, 1 H), 7.37 (d, J = 7.6 Hz, 1 H), 7.13 (t, J = 6.2 Hz, 1 H), 4.44 (t, J = 5.2 Hz, 1 H), 3.58 (d, J = 5.6 Hz, 1 H), 3.32 (s, 3 H), 3.31 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3), δ = 159.0, 149.2, 136.5, 122.6, 121.2, 83.9, 75.7, 59.2, 57.6 ppm. HRMS (EI-TOF): m/z [M+] calcd for C9H13NO2: 167.0946; found: 167.0947. 2-Phenyl-4-(tetrahydrofuran-2-yl)pyridine (3ea) Oil. 1H NMR (400 MHz, CDCl3): δ = 8.56 (d, J = 4.8 Hz, 1 H), 7.91 (d, J = 7.2 Hz, 2 H), 7.62 (s, 1 H), 7.41–7.31 (m, 3 H), 7.12 (d, J = 5.2 Hz, 1 H), 4.90 (t, J = 7.2 Hz, 1 H), 4.05 (q, J = 7.3 Hz, 1 H), 3.91 (q, J = 7.3 Hz, 1 H), 2.39–2.30 (m, 1 H), 1.98–1.91 (m, 2 H), 1.79–1.70 (m, 1 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.5 153.7, 149.5, 139.4, 128.9, 128.7, 127.0, 119.0, 117.4, 79.2, 68.9, 34.3, 25.8 ppm. HRMS (EI-TOF): m/z [M+] calcd for C15H15NO: 225.1154; found: 225.1158. 4-(1-Ethoxyethyl)-2-phenylpyridine (3ee) Oil. 1H NMR (400 MHz, CDCl3): δ = 8.58 (d, J = 5.2 Hz, 1 H), 7.92 (d, J = 7.2 Hz, 2 H), 7.61 (s, 1 H), 7.43–7.33 (m, 3 H), 7.12 (d, J = 6.0 Hz, 1 H), 4.40 (q, J = 6.4 Hz, 1 H), 3.40–3.32 (m, 2 H), 1.40 (d, J = 6.8 Hz, 3 H), 1.15 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.7, 154.1, 149.8, 139.4, 128.9, 128.7, 126.9, 119.6, 117.8, 76.8, 64.5, 23.8, 15.4 ppm. HRMS (EI-TOF): m/z [M+] calcd for C15H17NO: 227.1310; found: 227.1312.