Controlled Monoarylation of Dibromoarenes in Water with a Polymeric Palladium Catalyst

Abstract

A highly selective monoarylation of dibromoarenes was performed via the Suzuki-Miyaura cross-coupling with arylboronic acids with an amphiphilic polystyrene-poly(ethylene glycol) (PS-PEG) resin-supported phosphine-palladium complex in water ­under heterogeneous conditions to give bromobiaryls in high yields. Introduction of two different aryl groups on a aromatic moiety was achieved in a one-pot reaction by successive addition of two kinds of arylboronic acids under similar conditions. The polymeric ­palladium catalyst can be readily recovered and recycled.

Key words

Suzuki-Miyaura coupling - cross-coupling - biaryl ­formation - dibromoarenes

References

• For reviews, see:
• 2a Martin RE. Diederich F. Angew. Chem. Int. Ed.  1999,  38:  1350 
• 2b Watson MD. Fechtenkotter A. Mullen K. Chem. Rev.  2001,  101:  1267 
• For reviews, see:
• 3a Metal-Catalyzed Cross-Coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; Weinheim: 1998. 
• 3b Cross-Coupling Reactions: A Practical Guide, In Top. Curr. Chem.   Vol. 219:  Miyaura N. Springer-Verlag; Berlin-Heidelberg: 2002. 
• 3c J. Organomet. Chem. Vol. 653 (Special Issue), 30 Years of Cross-Coupling Reaction   Tamao K. Negishi E.-i. Hiyama T. 2002. 
• Monoarylating cross-couplings affording halobiaryls have been performed with arenes bearing different halogeno (or pseudo-halogeno) groups. For examples, see:
• 4a Kamikawa T. Hayashi T. Tetrahedron Lett.  1997,  38:  7087 
• 4b Kamikawa T. Hayashi T. J. Org. Chem.  1998,  63:  8922 
• 4c Sengupta S. Sadhukhan SK. Tetrahedron Lett.  1998,  39:  715 
• Monoalkylation of 1-[2,6-bis(trifluoromethanesulfonyl-oxy)phenyl]naphthalene has been achieved with high chemo- and stereoselectivity via Grignard cross-coupling, see:
• 5a Hayashi T. Niizuma S. Kamikawa T. Suzuki N. Uozumi Y. J. Am. Chem. Soc.  1995,  117:  9101 
• 5b Kamikawa T. Uozumi Y. Hayashi T. Tetrahedron Lett.  1996,  37:  3161 
• For reviews, see:
• 6a Modern Arene Chemistry   Astruc D. Wiley-VCH; Weinheim: 2002. 
• 6b Suzuki A. J. Organomet. Chem.  1999,  576:  147 
• 6c Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 
• 6d Suzuki Coupling, Organic Syntheses via Boranes   Vol. 3:  Suzuki A. Brown HC. Aldrich; Milwaukee: 2003. 
• For studies on polymer-supported palladium catalysts from the author’s group, see the following. π-Allylic substitution:
• 7a Uozumi Y. Danjo H. Hayashi T. Tetrahedron Lett.  1997,  38:  3557 
• 7b Danjo H. Tanaka D. Hayashi T. Uozumi Y. Tetrahedron  1999,  55:  14341 
• Cross-coupling:
• 7c Uozumi Y. Danjo H. Hayashi T. J. Org. Chem.  1999,  64:  3384 
• Carbonylation reaction:
• 7d Uozumi Y. Watanabe T. J. Org. Chem.  1999,  64:  6921 
• Suzuki-Miyaura coupling:
• 7e Uozumi Y. Nakai Y. Org. Lett.  2002,  4:  2997 
• Heck reaction:
• 7f Uozumi Y. Kimura T. Synlett  2002,  2045 
• Sonogashira reaction:
• 7g Uozumi Y. Kobayashi Y. Heterocycles  2003,  59:  71 
• Asymmetric alkylation:
• 7h Uozumi Y. Shibatomi K. J. Am. Chem. Soc.  2001,  123:  2919 
• Asymmetric amination:
• 7i Uozumi Y. Tanaka H. Shibatomi K. Org. Lett.  2004,  6:  281 
• Asymmetric catalysis:
• 7j Hocke H. Uozumi Y. Synlett  2002,  2049 
• 7k Hocke H. Uozumi Y. Tetrahedron  2003,  59:  619 
• 7l Hocke H. Uozumi Y. Tetrahedron  2004,  60:  9297 
• Asymmetric cycloisomerization:
• 7m Nakai Y. Uozumi Y. Org. Lett.  2005,  7:  291 

1

Present address: Graduate school of Engineering, Nagoya University, Nagoya, Japan.

8

The σ/σ⁺ value of bromo and phenyl groups: σ_µ/σ_µ ⁺ (Br) = +0.391/+0.405; σ_π/σ_π ⁺ (Br) = +0.232/+0.150; σ_µ/σ_µ ⁺ (Ph) = +0.06/+0.109; σ_π/σ_π ⁺ (Ph) = +0.01/-0.179.

9

Argo Gel NH₂ (Φ = 130 mm, loading value = 0.3 mmol/g) was used as a polymer support.

10

General Procedure for Monoarylation of Dibromoarenes.
A mixture of the dibromoarene 1 (0.4 mmol), the arylboronic acid 2 (0.4 mmol), 1 mol% palladium of 5 (4 µmol Pd), 8.4 mg of PPh₃ (32 µmol), and 40 µL of toluene in 4 mL of 2 M aqueous solution of K₂CO₃ was refluxed for 24 h. After being cooled, the mixture was filtered and collected resin beads were extracted with EtOAc. The GC yield and the ratio of 3:4 were determined by GC-MS analysis (internal standard: biphenyl) of the organic extract, and an analytically pure product was isolated by silica gel chromatography.

11

During the reaction, generation of precipitates on the resin surface was observed microscopically.

12

CAS Registry numbers of biaryl products: 3aA, 844856-52-6; 3aB, 844856-54-8; 3aD, 337535-27-0; 3bC, 251320-87-3; 3cC, 106475-19-8; 3iA, 675590-28-0.

13

3-Bromo-2′-methylbiphenyl (3aC). Compound 3aC was not isolated as an analytically pure sample. Characterization of 3aC was performed by GC-MS analysis: MS: m/z = 248, 246 [M⁺], 167 [M - Br] (base peak), 152, 139, 115, 82.

14

1-(3′-Bromobiphen-3-yl)ethanone (3aE). ¹H NMR (400 MHz, CDCl₃): δ = 8.12 (s, 1 H), 7.94 (d, J = 6.8 Hz, 1 H), 7.73 (d, J = 8.0 Hz, 2 H), 7.48-7.55 (m, 3 H), 7.31 (t, J = 8.0 Hz, 1 H), 2.65 (s, 3H). ¹³C NMR (100 MHz, CDCl₃): δ = 197.4, 142.0, 139.9, 137.4, 131.4, 130.5, 130.2, 130.0, 129.0, 127.6, 126.6, 125.6, 122.8, 26.8. MS: 274, 259, 231, 152, 76.

15

1-(4′-Bromobiphen-3-yl)ethanone (3cE). Compund 3cE was not isolated as an analytically pure sample. Characterization of 3cE was performed by GC-MS analysis: MS: m/z = 276, 274 [M⁺], 261, 259 [M - CH₃], 233, 231 [M - COCH₃], 152 [M - COCH₃-Br] (base peak), 126, 76.

16

4-Bromo-2,5,4′-trimethylbiphenyl (3dA).
¹H NMR (400 MHz, CDCl₃): δ = 7.42 (s, 1 H), 7.20 (d, J = 8.0 Hz, 2 H), 7.15 (d, J = 8.0 Hz, 2 H), 7.06 (s, 1H), 2.38 (s, 3 H), 2.36 (s, 3 H), 2.19 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 140.8, 137.7, 136.5, 134.7, 134.5, 133.5, 133.4, 131.9 (2 C), 128.7 (2 C), 123.1, 22.4, 21.3, 19.8. MS: m/z = 274, 195, 180, 165, 89.

17

1-Bromo-4-(4-methylphenyl)naphthalene (3eA). ¹H NMR (400 MHz, CDCl₃): δ = 8.31 (d, J = 8.4 Hz, 1 H), 7.89 (d, J = 8.4 Hz, 1 H), 7.79 (d, J = 7.6 Hz, 1 H), 7.57 (t, J = 6.8 Hz, 1 H), 7.44 (t, J = 6.8 Hz, 1 H), 7.32 (d, J = 8.0 Hz, 2 H), 7.27 (d, J = 8.4 Hz, 2 H), 7.22 (d, J = 7.6 Hz, 1 H), 2.43 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 140.2, 137.1, 136.8, 132.8, 131.9, 129.7, 129.3, 128.9, 127.3, 127.0 (2 C), 126.6, 126.5, 121.9, 21.4. MS: m/z = 296, 215, 202, 189, 107, 94.

18

3-Bromo-5-fluoro-4′-methylbiphenyl (3fA). ¹H NMR (400 MHz, CDCl₃): δ = 7.49-7.50 (m, 1 H), 7.41 (d, J = 8.0 Hz, 2 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.16-7.21 (m, 2 H), 3.14 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 164.0, 161.5, 144.7, 144.6, 138.3, 135.6 (2 C), 130.0, 126.8, 125.8, 125.7, 122.8, 122.7, 117.3, 117.1, 112.8, 112.6, 21.2. MS: m/z = 264, 183, 165, 91.

19

3,5-Dibromo-4′-methylbiphenyl (3gA). ¹H NMR (500 MHz, CDCl₃): δ = 7.58-7.61 (m, 3 H), 7.38-7.40 (m, 2 H), 7.21-7.24 (m, 2 H), 2.38 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 144.5, 138.2, 135.2, 123.0, 129.5, 128.5, 126.7, 123.0, 21.3. MS: m/z = 326, 245, 165, 139, 115, 82.

20

2-Bromo-6-(4-methylphenyl)pyridine (3hA). ¹H NMR (500 MHz, CDCl₃): δ = 7.88 (d, J = 8.5 Hz, 2 H), 7.64 (d, J = 7.0 Hz, 1 H), 7.55 (t, J = 7.5 Hz, 1 H), 7.36 (d, J = 8.0 Hz, 1 H), 7.26 (d, J = 8.5 Hz, 2 H), 2.40 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 158.4, 141.9, 139.5, 138.6, 134.7, 129.3 (2 C), 126.7 (2 C), 125.7, 118.4, 21.5. MS: m/z = 247, 168, 153, 141, 115, 83.

21

3-Methoxy-4′′-methyl[1,1′:3′,1′′]terphenyl(6). ¹H NMR (500 MHz, CDCl₃): δ = 7.77 (br s, 1 H), 7.51-7.54 (m, 4 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.34 (t, J = 7.5 Hz, 1 H), 7.20-7.24 (m, 3 H), 7.16 (t, J = 2.0 Hz, 1 H), 6.89 (dd, J = 7.5, 2.0 Hz, 1 H), 3.81 (s, 3 H), 2.37 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 159.7, 142.6, 141.4 (2 C), 138.0, 136.9, 129.5, 129.3, 128.9, 126.9 (2 C), 125.8, 125.7, 125.6, 119.6 (2 C), 112.9, 112.6, 55.3, 21.2. MS: m/z = 274, 215, 137, 115, 101.

22

2-(3-Methoxyphenyl)-6-(4-methylphenyl)pyridine(7). ¹H NMR (500 MHz, CDCl₃): δ = 8.03 (d, J = 8.0 Hz, 2 H), 7.76 (t, J = 2.5 Hz, 1 H), 7.70 (t, J = 8.0 Hz, 1 H), 7.67 (br d, J = 8.0 Hz, 1 H), 7.59 (t, J = 7.5 Hz, 2 H), 7.37 (t, J = 8.0 Hz, 1 H), 7.26 (d, J = 8.0 Hz, 2 H), 6.95 (dd, J = 7.5, 2.5 Hz, 1 H), 3.86 (s, 3 H), 2.38 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 159.7, 156.4, 156.1, 140.8, 138.6, 137.0, 136.4, 129.3, 129.1, 126.6, 119.2, 118.2, 114.4, 112.5, 55.3, 21.4. MS: m/z = 274, 245, 137.