Synlett 2003(6): 0852-0854
DOI: 10.1055/s-2003-38745
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Rapid and Efficient Synthesis of Functionalized Bipyridines

Yuan-Qing Fangb, Garry S. Hanan*a,b
a Département de chimie, Université de Montréal, Montréal, H3T 1J4, Canada
Fax: +1(514)3437586; e-Mail: garry.hanan@umontreal.ca;
b Department of Chemistry, University of Waterloo, Waterloo, N2L 3G1, Canada
Weitere Informationen

Publikationsverlauf

Received 25 September 2002
Publikationsdatum:
17. April 2003 (online)

Abstract

The Negishi reaction affords a mild and efficient method to convert chloro- and bromo-pyridines into functionalized 2,2′-bipyridines using commercially available starting materials. This method also extends to the conversion of dibromopyridines to 5- and 6-bromobipyridines, which are powerful synthons for incorporation into larger supramolecular systems.

19

General Procedure: A flame-dried Schlenk tube was charged with Pd(PPh3)4 and 2-halopyridine under argon. 2-Pyridylzinc bromide (THF solution) was then added by syringe. The mixture was stirred at r.t. for several hours, and was poured into an aq EDTA/Na2CO3 solution. After the precipitate had dissolved, the mixture was extracted with Et2O (3 ¥ 50 mL), and dried over Na2SO4. The solvent was evaporated and the residue was chromatographed on an alumina column (neutral, Brockmann I) with 10:1 hexane:EtOAc.

20

Compound 3c: 1: 4.5 mmol; 2c: 2.91 mmol; Pd(PPh3)4: 0.06 mmol. Chromatographed with 10:1 hexane:EtOAc as eluent to yield a colorless liquid. 1H NMR (300 MHz, CDCl3): δ = 8.64 (d, J = 4.8 Hz, 1 H, H6 ), 8.49 (d, J = 4.4 Hz, 1 H, H6), 7.80-7.73 (m, 2 H, H3 ,4 ), 7.56 (d, J = 7.7 Hz, 1 H, H 4), 7.27-2.22 (m, 1 H, H5 ), 7.18 (d, J = 7.8, 4.7 Hz, 1 H, H5 ), 2.46 (s, 3 H, Me). 13C NMR (75 MHz, CDCl3): δ = 159.0, 156.4, 148.6, 146.8, 139.2, 136.6, 132.3, 124.2, 123.1, 122.7, 20.0. FAB/NBA: 171.1 [MH+]. Compounds 3d-f: 3.0 mmol scale with 2 mol% Pd(PPh3)4, chromatographed with 10:1 hexane:EtOAc. NMR spectra are identical to those previously reported. [30]

21

Pd2(dba)3 and P(o-tolyl)3 or P(2-furyl)3 were tested as catalysts giving conversions of less than 20% with the same reaction conditions. Although recent results showed that Pd[P(t-Bu)3]2 is a powerful catalyst for coupling a broad range of aryl chlorides and organozinc halides, [22] the cost and the availability of the catalyst are a concern.

23

Compound 3g: 4.3 mmol scale with 3 mol% Pd(PPh3)4, chromatographed with a hexane:EtOAc solvent gradient (10:1 to 3:1). 1H NMR (500 MHz, CDCl3): δ = 8.80 (d, J = 4.9 Hz, 1 H), 8.68 (br, 2 H), 8.40 (d, J = 7.9 Hz, 1 H), 7.83 (td, J t = 7.7 Hz, J d = 1.5 Hz, 1 H), 7.49 (dd, J = 4.9, 1.2 Hz, 1 H), 7.35 (dd, J = 7.3, 4.9 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 157.6, 154.1, 150.1, 149.5, 137.3, 124.9, 124.8, 123.0, 121.4. 121.3, 116.8. Compound 3h: 1.0 mmol scale with 3 mol% Pd(PPh3)4. Extracted with CH2Cl2 and chromatographed with a hexane:EtOAc solvent gradient (10:1 to 3:1 to 1:1). Mp: 174-175 °C (EtOH). 1H NMR (300 MHz, CDCl3): δ = 9.42 (s, 1 H), 9.08 (s, 2 H), 8.84 (d, J = 5.0 Hz, 1 H), 8.75 (d, J = 4.6 Hz, 1 H), 8.43 (d, J = 7.9 Hz, 1 H), 8.33 (d, J = 4.1 Hz, 1 H), 7.83 (t, J = 7.7 Hz, 1 H), 7.64 (d, J = 7.7 Hz, 2 H, Ph), 7.56-7.45 (m, 3 H, Ph), 7.32 (dd, J = 7.4, 4.8 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 161.7, 157.2, 156.1, 155.4, 150.1, 149.5, 145.7, 137.0, 134.2, 133.2, 129.6, 129.2, 127.0, 123.9, 121.9, 121.2, 119.7. FAB/NBA: 311.1 [MH+]. Compound 3i: 3.0 mmol scale with 2 mol% Pd(PPh3)4, chromatographed with 13:1 hexane:EtOAc. NMR spectra are identical to those previously reported.24

26

Compound 5: 3.0 mmol scale with 2 mol% Pd(PPh3)4, chromatographed with 10:1 hexane:EtOAc. NMR spectra are identical to those previously reported.6

27

Compound 8: 2.0 mmol scale with 3 mol% Pd(PPh3)4, chromatographed with 10:1 hexane:EtOAc. NMR spectra are identical to those previously reported.28