Synlett 2014; 25(07): 995-1000
DOI: 10.1055/s-0033-1340871
letter
© Georg Thieme Verlag Stuttgart · New York

Metal-Free Iodination of Arylboronic Acids and the Synthesis of Biaryl Derivatives

Liting Niu
a   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
,
Hao Zhang
a   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
,
Haijun Yang
a   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
,
Hua Fu*
a   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
b   Key Laboratory of Chemical Biology (Guangdong Province), Graduate School of Shenzhen, Tsinghua University, Shenzhen 518057, P. R. of China   Fax: +86(10)62781695   Email: fuhua@mail.tsinghua.edu.cn
› Author Affiliations
Further Information

Publication History

Received: 25 December 2013

Accepted after revision: 05 February 2014

Publication Date:
14 March 2014 (online)


Abstract

A simple, general and efficient method is developed for the metal-free iodination of arylboronic acids. The protocol uses very cheap molecular iodine as the halide source and potassium carbonate as the base. The method is highly tolerant of various functional groups present in the substrates. Importantly, the iodination strategy can also be applied very effectively in the one-pot, two-step synthesis of biaryl derivatives.

Supporting Information

 
  • References and Notes


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  • 13 K2CO3 (99.997%) was purchased from Alfa Aesar and contains Si (1 ppm), Ca (2 ppm) and Na (4 ppm); other elements including: Al, Bi, Cr, Fe, Mn, Sr, V, Sb, B, Co, Pb, Mo, Te, Zn, As, Cd, Cu, Li, Ni, Ag, Sn, Zr, Ba, In, Mg, P and Ti were not detected by ICP/AA (data provided by Alfa Aesar).
  • 14 Aryl Iodides (2); General Procedure Arylboronic acid 1 (0.5 mmol) and K2CO3 (1 mmol, 138.0 mg) were added to a 20 mL Schlenk-tube equipped with a magnetic stir bar. The tube was evacuated twice and back-filled with N2. MeCN (2 mL) and I2 (0.75 mmol, 191 mg) were added to the tube at r.t. under a stream of N2, and the tube was sealed and placed into a pre-heated oil bath at 80 °C for 8–12 h. The resulting solution was cooled to r.t. and H2O (10 mL) was added. The aq layer was extracted with EtOAc (3 × 5 mL). For products 2s and 2t, HCl (1 M) was added to the aq solution until pH 2 before extraction. The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation. Purification of the residue by column chromatography on silica gel provided the desired product 2av. Data for three representative examples are provided. PE = petroleum ether. 1-Iodo-4-methoxybenzene (2g) [16] Eluent: PE; yield: 93.6 mg (80%); white solid; mp 49–50 °C. 1H NMR (300 MHz, CDCl3): δ = 7.54 (d, J = 8.9 Hz, 2 H), 6.68 (d, J = 8.9 Hz, 2 H), 3.77 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 159.6, 138.3, 116.5, 82.8, 55.4. EI-MS: m/z [M]+ = 234.0. 1-Chloro-3-iodobenzene (2k) [17] Eluent: PE; yield: 86.8 mg (73%); yellow oil. 1H NMR (300 MHz, CDCl3): δ = 7.75 (s, 1 H), 7.60 (d, J = 7.9 Hz, 1 H), 7.33 (d, J = 7.9 Hz, 1 H), 7.02 (t, J = 7.9 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 137.3, 135.8, 135.2, 131.1, 128.1, 94.3. EI-MS: m/z [M]+ = 237.9. 1-Iododibenzo[b,d]furan (2v) [8a] Eluent: PE–EtOAc, 20:1; yield: 129.4 mg (88%); white solid; mp 48–49 °C. 1H NMR (300 MHz, CDCl3): δ = 7.90–7.77 (m, 3 H), 7.65 (d, J = 7.9 Hz, 1 H), 7.47 (d, J = 6.9 Hz, 1 H), 7.37 (d, J = 6.9 Hz, 1 H), 7.08 (t, J = 7.9 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 156.5, 155.7, 136.0, 127.8, 124.6, 124.5, 124.4, 123.3, 121.3, 120.6, 112.2, 75.6. EI-MS: m/z [M]+ = 294.0.
  • 15 Biaryls (3); General Procedure Arylboronic acid 1 (0.5 mmol) and K2CO3 (1 mmol, 138.0 mg) were added to a 20 mL Schlenk-tube equipped with a magnetic stir bar. The tube was evacuated twice and back-filled with N2. MeCN (2 mL) and I2 (0.75 mmol, 191 mg) were added to the tube at r.t. under a stream of N2, and the tube was sealed and placed into a pre-heated oil bath at 80 °C for 8–12 h. The resulting solution was cooled to r.t., and then arylboronic acid 1′ (0.75 mmol) and Pd(OAc)2 (0.025 mmol, 5.6 mg) were added, and the mixture stirred at 80 °C for 12–16 h. The resulting solution was cooled to r.t. and H2O (10 mL) was added. The aq layer was extracted with EtOAc (3 × 5 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation, and the residue was purified by column chromatography on silica gel to provide the desired product 3av. Data for three representative examples are provided. 3-Methoxy-1,1′-biphenyl (3c) Eluent: PE–EtOAc, 100:1; yield: 70.8 mg (77%); yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.63 (d, J = 6.9 Hz, 2 H), 7.47 (t, J = 7.3 Hz, 2 H), 7.41–7.37 (m, 2 H), 7.22 (d,  = 8.2 Hz, 1 H), 7.17 (s, 1 H), 6.94 (d, J = 8.2 Hz, 1 H), 3.89 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 160.1, 142.9, 141.2, 129.9, 128.9, 127.5, 127.3, 119.8, 113.0, 112.8, 55.4. EI-MS: m/z [M]+ = 184.1. Methyl 4′-Methyl-[1,1′-biphenyl]-4-carboxylate (3n) Eluent: PE–EtOAc, 100:1; yield: 98.4 mg (87%); white solid; mp 102–103 °C. 1H NMR (400 MHz, CDCl3): δ = 8.09 (d, J = 8.7 Hz, 2 H), 7.64 (d, J = 8.2 Hz, 2 H), 7.52 (d, J = 8.2 Hz, 2 H), 7.27 (d, J = 8.7 Hz, 2 H), 3.93 (s, 3 H), 2.40 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 167.1, 145.7, 138.2, 137.2, 130.2, 129.7, 128.7, 127.2, 126.9, 52.2, 21.2. EI-MS: m/z [M]+ = 226.1. 3′-Methyl-[1,1′-biphenyl]-4-carbonitrile (3q) Eluent: PE–EtOAc, 100:1; yield: 78.2 mg (81%); colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.2 Hz, 2 H), 7.67 (d, J = 8.2 Hz, 2 H), 7.39–7.36 (m, 3 H), 7.23 (d, J = 6.0 Hz, 1 H), 2.43 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 145.9, 139.3, 138.9, 132.6, 129.5, 129.1, 128.1, 127.8, 124.5, 119.1, 110.9, 21.6. EI-MS: m/z [M]+ = 193.1.
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