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Synlett 2013; 24(20): 2687-2690
DOI: 10.1055/s-0033-1340011
letter
© Georg Thieme Verlag Stuttgart · New York

Sequential Chelation-Assisted Aromatic C–H Functionalisation via Catalytic meta Sulfonation

William R. Reynolds
a   Centre for Sustainable Chemical Technologies, University of Bath, Claverton Down, Bath, BA2 7AY, UK
b   Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK   Fax: +44(1225)386231   Email: c.g.frost@bath.ac.uk
,
Po Man Liu
b   Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK   Fax: +44(1225)386231   Email: c.g.frost@bath.ac.uk
,
Gabriele Kociok-Köhn
b   Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK   Fax: +44(1225)386231   Email: c.g.frost@bath.ac.uk
,
Christopher G. Frost*
a   Centre for Sustainable Chemical Technologies, University of Bath, Claverton Down, Bath, BA2 7AY, UK
b   Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK   Fax: +44(1225)386231   Email: c.g.frost@bath.ac.uk
› Author Affiliations
Further Information

Publication History

Received: 30 August 2013

Accepted: 17 September 2013

Publication Date:
05 November 2013 (online)

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Abstract

The sequential functionalisation of 2-phenylpyridine is presented using selective ortho- and meta-directing processes. It was found that performing a reaction sequence with meta functionalisation first followed by ortho functionalisation provided novel reaction products in good yields and with complete regioselectivity.

Key words

catalysis - green chemistry - palladium - regioselectivity - ruthenium

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References

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  • 10 meta-Sulfonation; General Procedure: To a nitrogen-purged carousel tube was added [RuCl2(p-cymene)]2 (0.12 mmol, 0.060 g), phenylpyridine derivative (2 mmol), sulfonyl chloride (6 mmol), potassium carbonate (4 mmol, 0.552 g), and acetonitrile (5 mL). The reaction was heated to 120 °C with stirring for 15 h before being cooled to r.t. The reaction mixture was washed with brine, extracted with dichloromethane, dried over MgSO4, and the solvent was removed. The crude mixture was purified by flash column chromatography.Compound 3b: According to the general procedure, from 2-(2-methoxy)phenylpyridine (2 mmol, 0.372 g) and p-toluenesulfonyl chloride (6 mmol, 1.144 g) in MeCN (5 mL), the title compound was obtained by flash column chromatography eluting with CH2Cl2–2-propanol (1:0.01) to give a white solid (12% yield); mp 160–163 °C. IR (neat): ν = 2924.21, 1590.54, 1464.65, 1140.51, 1088.93, 989.91, 776.29, 685.44, 654.76 cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.68 (d, J = 4.7 Hz, 1 H), 8.17 (dd, J = 7.9, 1.8 Hz, 1 H), 7.93 (dd, J = 7.7, 1.7 Hz, 1 H), 7.86 (d, J = 8.3 Hz, 2 H), 7.68 (d, J = 3.6 Hz, 2 H), 7.35 (t, J = 7.8 Hz, 1 H), 7.29 (d, J = 8.0 Hz, 2 H), 7.24 (q, J = 4.7 Hz, 1 H), 3.35 (s, 3 H), 2.39 (s, 3 H).13C NMR (75 MHz, CDCl3): δ = 156.3, 154.5, 150.0, 144.0, 138.9, 137.5, 136.5, 135.6, 135.0, 130.0, 129.4, 128.2, 124.4, 124.2, 122.7, 62.2, 21.7. HRMS calcd for [M+H]+: 340.1008; found: 340.1090.Compound 18a: According to the general procedure, from 2-(p-tolyl)pyridine (2 mmol, 0.341 ml) and 4-bromophenyl-sulfonyl chloride (6 mmol, 1.533 g), the title compound was obtained by flash column chromatography eluting with hexane–EtOAc (4:1), followed by recrystallisation from ethanol to give a white solid (46% yield); mp 196–198 °C. IR (neat): ν = 2974.01, 1570.40, 1431.29, 1308.22, 1148.62, 1105.96, 1067.43, 1006.20, 808.79, 771.38, 742.25, 614.92 cm–1. 1H NMR (250 MHz, CDCl3): δ = 8.80 (d, J = 1.9 Hz, 1 H), 8.70 (d, J = 4.7 Hz, 1 H), 8.18 (dd, J = 7.9, 1.9 Hz, 1 H), 7.84 – 7.73 (m, 2 H), 7.74 (d, J = 8.7 Hz, 2 H), 7.61 (d, J = 8.7 Hz, 2 H), 7.34 (d, J = 8.0 Hz, 1 H), 7.31 – 7.25 (m, 1 H), 2.45 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 155.3, 149.8, 140.3, 138.8, 138.5, 138.1, 137.2, 133.5, 132.4, 132.1, 129.3, 128.4, 127.8, 122.9, 120.6, 20.2. HRMS calcd for [M+H]+: 389.9941; found: 389.9960
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  • 12 ortho-Bromination; General Procedure: To a clean, dry carousel tube, Cu(OAc)2 (1 mmol, 0.18 g) the required substrate (1 mmol), C2Cl4Br2 (2 mmol, 0.65 g) and acetonitrile (5 mL) were added in air. The reaction was heated to 130 °C with stirring for 24 h before being cooled to r.t. The reaction mixture was washed with sat. aq NaHSO3, extracted with dichloromethane, filtered through celite, dried over MgSO4, and the solvent was removed. The crude mixture was purified by column chromatography.Compound 6: According to the general procedure, from compound 2 (1 mmol, 0.31 g), the title compound was obtained after purification by flash column chromatography eluting with hexane–EtOAc–Et3N (4:1:0.01) to give a white solid (87% yield); mp 198–200 °C. IR (neat): ν = 2925.64, 1592.48, 1478.05, 1402.41, 1311.17, 1296.68, 1151.63, 1107.45, 814.28, 692.52, 646.22 cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.61 (d, J = 4.7 Hz, 1 H), 8.50 (d, J = 2.3 Hz, 1 H), 8.12 (d, J = 8.2 Hz, 1 H), 8.02 (t, J = 8.5 Hz, 1 H), 7.90 (d, J = 8.2 Hz, 2 H), 7.84 (dd, J = 8.7, 2.1 Hz, 1 H), 7.47–7.40 (m, 1 H), 7.40–7.31 (m, 2 H), 7.15 (d, J = 8.7 Hz, 1 H), 2.46 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 164.2, 155.9, 145.6, 143.8, 139.4, 138.7, 131.4, 130.8, 130.0, 127.4, 126.5, 122.7, 119.7, 118.6, 21.6. HRMS calcd for [M+H]+: 389.9986; found: 390.0062.Compound 18: According to the general procedure, from compound 18a (1 mmol, 0.39 g), the title compound was obtained after purification by flash column chromatography eluting with hexane–EtOAc–Et3N (4:1:0.01) to give a white solid (76% yield); mp 162–166 oC. IR (neat): ν = 3088.98, 2927.31, 1712.99, 1571.77, 1456.70, 1304.32, 1148.64, 1058.78, 1007.94, 892.75, 825.23, 751.21, 733.05 cm–1. 1H NMR (250 MHz, CDCl3): δ = 8.74 (ddd, J = 4.9, 1.8, 0.9 Hz, 1 H), 8.36 (s, 1 H), 7.87–7.71 (m, 3 H), 7.69–7.54 (m, 4 H), 7.35 (ddd, J = 7.6, 4.9, 1.2 Hz, 1 H), 2.43 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 156.5, 149.6, 139.9, 139.8, 139.1, 138.0, 137.4, 136.3, 132.5, 132.3, 129.3, 128.7, 128.0, 124.8, 123.1, 19.8. HRMS calcd for [M+H]+: 467.9013; found: 467.9096.
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