Iridium/N-heterocyclic carbene-catalyzed C–H borylation of arenes by diisopropylaminoborane

Catalytic C–H borylation of arenes has been widely used in organic synthesis because it allows the introduction of a versatile boron functionality directly onto simple, unfunctionalized arenes. We report herein the use of diisopropylaminoborane as a boron source in C–H borylation of arenes. An iridium(I) complex with 1,3-dicyclohexylimidazol-2-ylidene is found to efficiently catalyze the borylation of arenes and heteroarenes. The resulting aminoborylated products can be converted to the corresponding boronic acid derivatives simply by treatment with suitable diols or diamines.

VI Spectroscopic data S11 S2 I. General information 1 H NMR and 13 C NMR spectra were recorded on a JEOL ECS-400 spectrometer in CDCl 3 or C 6 D 6 with tetrachloroethane as the internal standard. Data are reported as follows: chemical shift in ppm (), multiplicity (s = singlet, d = doublet, t = triplet, and m = multiplet), coupling constant (Hz), and integration. Infrared spectra (IR) were obtained using a JASCO FT/IR-4200 spectrometer; absorptions are reported in reciprocal centimeters with the following relative intensities: s (strong), m (medium), or w (weak). Mass spectra and high resolution mass spectra (HRMS) were obtained on a JEOL JMS-700 spectrometer. Analytical gas chromatography (GC) was carried out on a Shimazu GC-2014 gas chromatograph, equipped with a flame ionization detector. Melting points were determined using a Yamato melting point apparatus. Column chromatography was performed with SiO 2 (silicycle SilicaFlash F60 (230-400 mesh)).
The mixture was allowed to warm to room temperature and stirred for 4 h. The crude mixture was concentrated under vacuum and the residue was taken with toluene (100 mL), washed with water (4 × 100 mL). The organic phase was driedusing Na 2 SO 4 and concentrated under reduced pressure to give an amine-borane complex as a colorless oil. The resulting amine-borane complex was then refluxed at 195 °C for 9 h, and the diisopropylaminoborane was distilled under N 2 to give 17.2 g (76% yield).
The effect of the amount of [Ir(OMe)(cod)] 2 was also examined using 10 (0.50 mmol), 1g (1.0 mmol), [Ir(OMe)(cod)] 2 , ICy·HCl and NaOt-Bu in methylcyclohexane (1.0 mL) at 110 °C for 4 h (Table S6). Under these conditions, we were able to reduce the catalyst loading to 10 mol % without any loss of the yield of the product (Entry 4). This result indicate that benzo[b]thiophene is more reactive than N-methylindole toward this borylation.
Under these conditions, ICy·HCl was found to be an optimal ligand with a borylated product 17-B being formed in 53% (Entry 1).
Under these conditions, 110 °C was found to be an optimal temperature with a borylated product 17-B being formed in 47% (Entry 4).
Under these conditions, 18 h was found to be an optimal reaction time with a borylated product 17-B being formed in 53% (Entry 7).

IV. Typical procedure
Method A: Procedure for the Ir-catalyzed borylation of heteroarenes using 1g.
In a glovebox filled with nitrogen, [Ir(OMe)(cod)] 2 (33.1 mg, 0.050 mmol, 0.10 equiv), ICy·HCl (26.2 mg, 0.10 mmol, 0.20 equiv), NaOt-Bu (19.2 mg, 0.20 mmol, 0.40 equiv) and methylcyclohexane (1.0 mL) were added to a 10 mL-sample vial with a Teflon-sealed screwcap, and stirred for 5 min at room temperature. A heteroarene (0.50 mmol, 1.0 equiv) and 1g (113.1 mg, 2.0 equiv) were added, and then the cap was screwed on seal the vial. The vial was stirred at 110 °C for 4 h. The reaction mixture was cooled to room temperature. Pinacol (236 mg, 2.0 mmol) in THF (2.0 S10 mL) was added and the reaction mixture was stirred under N 2 at room temperature for 1.5 h. The crude mixture was filtered through a pad of Celite and eluted with EtOAc. The filtrate was concentrated in vacuo and sampled for analysis by 1 HNMR spectroscopy using 1,2-dichloroethane as an internal standard. The residue was purified by flash column chromatography over silica gel eluting with hexane/EtOAc. Product-containing fractions were concentrated in vacuo to give a pure borylated product.
Method B: Procedure for the Ir-catalyzed borylation of arenes using 1g.
In a glovebox, [Ir(OMe)(cod)] 2 (33.1 mg, 0.050 mmol, 0.10 equiv), ICy•HCl (26.2 mg, 0.10 mmol, 0.20 equiv), NaOt-Bu (19.2 mg, 0.20 mmol, 0.40 equiv) and benzene (1.0 mL) were added to a 10 mL-sample vial with a Teflon-sealed screwcap, and stirred for 5 min at room temperature. 1g (113.1 mg, 1.0 mmol, 2.0 equiv) was added, and then the cap was screwed on to seal the vial. The vial was stirred at 110 °C for 18 h. The reaction mixture was cooled to room temperature. Pinacol (236 mg, 2.0 mmol, 4.0 equiv) in THF (2.0 mL) was added and the reaction mixture was stirred for 1.5 h at room temperature under N 2 . The crude mixture was filtered through a pad of Celite and eluted with EtOAc. The filtrate was concentrated in vacuo and sampled for analysis by 1 H NMR spectroscopy using 1,2-dichloroethane as an internal standard. The residue was purified by flash column chromatography over silica gel eluting with hexane/EtOAc. Product-containing fractions were concentrated in vacuo to give a pure borylated product.
A procedure for the gram scale synthesis of 2-borylated 10.
The reaction mixture was cooled to room temperature. Pinacol (2.57 g, 22.0 mmol, 4.0 equiv) in THF (16 mL) was added and the reaction mixture was stirred under N 2 at room temperature for 1.5 h.
The crude mixture was filtered through a pad of Celite and eluted with EtOAc. The filtrate was concentrated in vacuo and sampled for analysis 1 H NMR spectroscopy using 1,2-dichloroethane as an internal standard. The residue was purified by flash column chromatography over silica gel eluting with hexane/EtOAc (40/1) solution. Product-containing fractions were concentrated in vacuo to give 10-B as a white solid (1.25 g, 74%).
Method A was used. The product was obtained as a mixture of mono and diborylated thiophenes. It was possible to purify two products by flush column chromatography over silica gel.
After purification by flash column chromatography over silica gel eluting with hexane/AcOEt = 40/1, a mixture of two isomers was obtained. GC/MS analysis revealed the two isomers of the borylated products had an m/z of 272 (M + ). The identity and ratio of each of the two isomers were determined by comparing the 1 H NMR spectrum of the product mixture with those reported in the literature. 9 The resonances specific to each isomer are as follows: 1 H NMR (C 6 D 6 , 399.78 MHz): 7.96 (d, J = 8.2 Hz, 1H, para isomer, H a ), 8.46 (s, 1H, meta isomer, H b ).