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Synlett 2006(4): 0555-0558  
DOI: 10.1055/s-2006-932471
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis and Reaction of the First Oxazol-4-ylboronates: Useful Reagents for the Preparation of the Oxazole-Containing Biaryl Compounds

Hiroshi Arakia, Tadashi Katohb, Munenori Inoue*a,c
a Department of Electronic Chemistry, Tokyo Institute of Technology, Nagatsuta, Yokohama 226-8502, Japan
b Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
c Sagami Chemical Research Center, 2743-1 Hayakawa, Ayase, Kanagawa 252-1193, Japan
Fax: +81(467)774113; e-Mail: inoue@sagami.or.jp;
Further Information

Publication History

Received 3 December 2005
Publication Date:
20 February 2006 (online)

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Abstract

The first oxazol-4-ylboronates were prepared from the corresponding 4-bromo- and 4-trifluoromethanesulfonyloxy-oxazoles. The Suzuki coupling using the resulting boron reagents with various aryl halides, including benzene, pyridine, oxazole and thiazole rings, in the presence of palladium catalyst proceeded to produce the oxazole-containing biaryl compounds in moderate to good yields.

Key words

oxazoles - oxazol-4-ylboronates - Suzuki coupling - biaryl compounds - palladium-catalyzed cross-coupling

    References and Notes

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12

Preparation of 2-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)oxazole ( 2).
A suspension of Pd2(dba)3·CHCl3 (120 mg, 0.13 mmol) and tricyclohexylphosphine (220 mg, 0.78 mmol) in 1,4-dioxane (60 mL) was stirred for 30 min at r.t. under Ar. Bis(pinacolato)diboron (1.46 g, 5.7 mmol), 2-phenyl-4-tri-fluoromethanesulfonyloxyoxazole (1, 1.53g, 5.2 mmol) and KOAc (769 mg, 7.8 mmol) were successively added to the resulting solution. After being at reflux for 2 h, the reaction mixture was diluted with Et2O (300 mL). The resulting mixture was washed with H2O (100 mL) and then dried over Na2SO4. Concentration of the solvent in vacuo gave a residue, which was purified by silica gel column chromato-graphy (hexane-EtOAc, 20:1 to 1:1) to give 2-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)oxazole (2). After recrystallization from hot hexane, pure 2 (1.06 g, 75%) was obtained as colorless needles; mp 124-125 °C. 1H NMR (500 MHz, CDCl3): δ = 1.38 (12 H, s), 7.44 (3 H, m), 8.07 (1 H, s), 8.14 (2 H, m). 13C NMR (125 MHz, CDCl3): δ = 24.8, 84.3, 126.9, 127.3, 128.6, 130.4, 148.0, 162.8; IR (neat) 2996, 2973, 1567, 1363, 1319, 1081, 692 cm-1. HRMS (EI): m/z calcd for C15H18BNO3 [M+]: 271.1380; found: 271.1374.

14

Preparation of 5-Methyl-2-phenyl-4-(4,4,5,5-tetra-methyl-1,3,2-dioxaborolan-2-yl)oxazole ( 4).
n-BuLi in n-hexane (1.58 M, 0.42 mL, 0.67 mmol) was added to a stirred solution of 4-bromo-5-methyl-2-phenyl-oxazole (3, 144 mg, 0.65 mmol) in THF (3 mL) at -78 °C under Ar. After 30 min, triisopropylborate (0.17 mL, 0.73 mmol) was added to the resulting solution and stirred for 1 h at the same temperature. The reaction mixture was allowed to warm to r.t. and stirred for 1 h. Pinacol (86 mg, 0.73 mmol) and glacial AcOH (42 µL, 0.73 mmol) were added to the resulting solution and the resulting mixture was stirred for 1 h. The reaction mixture was diluted with Et2O (30 mL) and washed with H2O (10 mL) and then dried over Na2SO4. Concentration of the solvent in vacuo gave a residue, which was purified by silica gel column chromatography (hexane-EtOAc, 1:1) to give 5-methyl-2-phenyl-4-(4,4,5,5-tetra-methyl-1,3,2-dioxaborolan-2-yl)-oxazole (4). After recryst-allization from hot hexane, pure 4 (95 mg, 55%) was obtained as colorless needles; mp 108-109 °C. 1H NMR (500 MHz, CDCl3): δ = 1.36 (12 H, s), 2.56 (3 H, s), 7.41 (3 H, m), 8.10 (2 H, m). 13C NMR (125 MHz, CDCl3): δ = 11.8, 24.9, 83.9, 126.5, 127.6, 128.5, 129.9, 160.1, 161.0. IR (neat): 2979, 1593, 1407, 1382, 1317, 1141, 1085, 1050, 696 cm-1. HRMS (EI): m/z calcd for C16H20BNO3 [M+]: 285.1536; found: 285.1532.

15

Although both K2CO3 and K3PO4 worked well in the coupling reaction of 2 with bromobenzene, we chose K2CO3 as a base for further applications due to its milder basicity.

16

General Procedure of the Suzuki Coupling [Synthesis of 2,4-Diphenyloxazole ( 5)]. A solution of 2 (60 mg, 0.22 mmol), bromobenzene (23 µL, 0.22 mmol), tetrakis(triphenylphosphine)palladium(0) (13 mg, 11 µmol) and K2CO3 (92 mg, 0.66 mmol) in DMF (1 mL) was heated at 100 °C for 30 min under Ar. The reaction mixture was diluted with Et2O (30 mL) and washed with H2O (10 mL) and then dried over Na2SO4. Concentration of the solvent in vacuo gave a residue, which was purified by silica gel column chromatography (hexane-EtOAc, 20:1) to give 2,4-diphenyloxazole (5, 43 mg, 88%) as a white solid. All characterization data of 5 were compatible with the literature. [13]