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Synlett 2012(6): 938-942  
DOI: 10.1055/s-0031-1290602
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Palladium-Catalyzed Benzylic Cross-Couplings of Pyridine N-Oxides

Wenpeng Mai*, Jinwei Yuan, Zhicheng Li, Liangru Yang, Yongmei Xiao, Pu Mao, Lingbo Qu
Chemistry and Chemical Engineering School, Henan University of Technology, Zhengzhou Henan 450001, P. R. of China
Fax: +86(371)67756715; e-Mail: wpmai@yahoo.com.cn;
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Publikationsverlauf

Received 19 December 2011
Publikationsdatum:
02. März 2012 (online)

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Abstract

Palladium-catalyzed C-H couplings (C SP ³ -C SP ² ) of pyridine N-oxides with benzyl chloride derivatives is reported. It provides a novel and easy process for the synthesis of 2-benzylpyridine derivatives through benzylic cross-couplings of pyridine N-oxides.

Key words

palladium - benzylation - pyridine N-oxide - C-H couplings

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14

General Procedure: An 50-mL vial was charged with magnetic stir bar, pyridine N-oxide (1a; 1.5 mmol), benzyl chloride (2a; 1.0 mmol), Pd(OAc)2 (0.05 mmol), t-Bu3P-HBF4 (0.1 mmol), K2CO3 (2.0 mmol), followed by anhyd toluene (3 mL). After stirring at 110 ˚C for 16 h, the reaction mixture was filtered through Celite (washed with MeOH and CH2Cl2). The combined organic phase was then evaporated under reduced pressure and the isolated yield was obtained by flash chromatography column on silica gel (gradient eluent of MeOH in CH2Cl2: 1-5%).
2-Benzylpyridine N -Oxide (3aa): yellow solid. ¹H NMR (400 MHz, CDCl3): δ = 8.32 (d, J = 2.8 Hz, 1 H), 7.33-7.40 (m, 2 H), 7.28-7.31 (m, 3 H), 6.95-7.19 (m, 2 H), 6.93-6.95 (m, 1 H), 4.28 (s, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 151.9, 139.4, 136.2, 129.7, 128.8, 127.1, 125.8, 125.6, 123.6, 36.5. MS (ESI): m/z = 186.0 [M + 1]+. HRMS (ESI): m/z [M + H]+ calcd for C12H12NO+: 186.0919; found: 186.0913.
2-(2-Methylbenzyl)pyridine N -Oxide (3ab): ¹H NMR (400 MHz, CDCl3): δ = 8.32 (d, J = 6.4 Hz, 1 H), 7.10-7.27 (m, 6 H), 6.71 (d, J = 7.2 Hz, 1 H), 4.25 (s, 2 H), 2.19 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 151.3, 139.4, 137.2, 134.4, 130.6, 127.5, 126.5, 125.7, 125.9, 125.1, 123.4, 34.4, 19.3. HRMS (ESI): m/z [M + H]+ calcd for C13H14NO+: 200.1075; found: 200.1073.
2-(4-Fluorobenzyl)pyridine N -Oxide (3ac): pale yellow solid. ¹H NMR (400 MHz, CDCl3): δ = 8.35 (d, J = 5.2 Hz, 1 H), 7.19-7.28 (m, 4 H), 6.99-7.07 (m, 3 H), 4.26 (s, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 163.2, 160.7, 151.6, 149.5, 131.9, 131.2, 125.7, 123.7, 123.9, 115.8, 35.8. HRMS (ESI): m/z [M+H]+ calcd for C12H11FNO+: 204.0825; found: 204.0827.
2-(3-Trifluoromethylbenzyl)pyridine N -Oxide (3ad): ¹H NMR (400 MHz, CDCl3): δ = 8.28-8.30 (m, 1 H), 7.44-7.55 (m, 4 H), 7.18-7.21 (m, 2 H), 7.00-7.03 (m, 1 H), 4.32 (s, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 150.8, 139.6, 137.3, 137.1, 133.0, 131.2, 130.9, 128.6, 129.3, 126.2, 126.17, 126.13, 126.1, 125.9, 125.7, 125.4, 124.1, 123.99, 123.95, 123.91, 122.66, 36.4. HRMS (ESI): m/z [M + H]+ calcd for C13H11F3NO+: 254.0793; found: 254.0796.