Iridium-catalysed regioselective borylation of carboranes via direct B–H activation

Carboranes are carbon–boron molecular clusters, which can be viewed as three-dimensional analogues to benzene. They are finding many applications in medicine, materials and organometallic chemistry. On the other hand, their exceptional thermal and chemical stabilities, as well as 3D structures, make them very difficult to be functionalized, in particular the regioselective functionalization of BH vertex among ten similar B–H bonds. Here we report a very efficient iridium-catalysed borylation of cage B(3,6)–H bonds of o-carboranes with excellent yields and regioselectivity using bis(pinacolato)diboron (B2pin2) as a reagent. Selective cage B(4)–H borylation has also been achieved by introducing a bulky TBDMS (tert-butyldimethylsilyl) group to one cage carbon vertex. The resultant 3,6-(Bpin)2-o-carboranes are useful synthons for the synthesis of a wide variety of B(3,6)-difunctionalized o-carboranes bearing cage B–X (X=O, N, C, I and Br) bonds.

The residue was subjected to flash column chromatography on silica gel (230-400 mesh) using n-hexane and ethyl acetate (10/1 in v/v) as eluent to give a mixture of product and B 2 pin 2 . Removal of B 2 pin 2 via sublimation at 90 o C under vacuum (0.1 torr) afforded a pure product 3a (3.75 g, 95%).

7.
To a solution (2 mL) of 7 (0.3 mmol) (acetone for 7a and 7b; MeOH/DCM (2/1 in v/v) for 7c) was added CsF (182 mg, 1.2 mmol). The mixture was stirred at room temperature for 1 h for 7a,7b and 20 min for 7c. After filtration, the filtrate was concentrated to dryness in vacuo. The residue was subjected to flash column chromatography on silica gel (230−400 mesh) using n-hexane and ethyl acetate (10/1 in v/v) as eluent to give product 8.

Preparation of 3,6-Diphenyl-o-carborane (9)
An oven-dried Schlenk flask equipped with a stir bar was charged with 3a (198 mg, 0.5 mmol), bromobenzene (236 mg, 1.5 mmol), Pd(PPh 3 ) 4 (115 mg, 0.1 mmol) and Cs 2 CO 3 (490 mg, 1.5 mmol), followed by dry cyclohexane (5 mL). The flask was closed under an atmosphere of nitrogen and stirred at 150 o C (bath temperature) for 8 h. After cooled to room temperature, water (10 mL) and 30% H 2 O 2 (5 mL) aqueous solution were successively added and the mixture was stirred at room temperature for 15 min. After extraction with diethyl ether (10 mL x 3), the ether solutions were S22 combined and concentrated to dryness in vacuo. The residue was subjected to flash column chromatography on silica gel (230-400 mesh) using n-hexane and ethyl acetate (100/1 in v/v) as eluent to give a white solid. Removal of biphenyl byproduct via sublimation at 90 o C under vacuum (0.1 torr) gave the pure 3,6-diphenyl-o-carborane (9) as a white solid (120 mg, 81%).
After cooling to room temperature, water (10 mL) and 30% H 2 O 2 (5 mL) aqueous solution were successively added and the mixture was stirred at room temperature for 15 min.. After extraction with diethyl ether (10 mL x 3), the ether solutions were combined and concentrated to dryness in vacuo. The residue was subjected to flash column chromatography on silica gel (230-400 mesh) using n-hexane as eluent to give 11.
The resulting mixture was heated in a closed flask at 80 o C for 8 h. After hydrolysis with water (10 mL) and extraction with diethyl ether (10 mL x 3), the ether solutions were combined and concentrated to dryness in vacuo. The residue was subjected to flash column chromatography on S25 silica gel (230-400 mesh) using n-hexane/ethyl acetate (4/1 in v/v) as eluent to give 13 as a white solid (78 mg, 90%).

Preparation of 3,6-Ditriazolyl-o-carborane by Click Reaction.
Compound 14 (68 mg, 0.3 mmol) and diethyl but-2-ynedioate (123 mg, 0.72 mmol) were dissolved in toluene (1 mL). The resulting mixture was stirred at 95 o C for 5 h. After removal of the solvent in vacuo, the residue recrystallized from n-hexane/diethyl ether (5/1 in v/v) to give 15 as a white solid (141 mg, 83%). To a solution of 3a (396 mg, 1.0 mmol) in ether (15 mL) was added diethanolamine (260 mg, 2.5 S27 mmol). After a few minutes, a white precipitate was formed, and the reaction was allowed to continue until the starting material was completely consumed as monitored by TLC (∼18 h). The precipitate was then filtered off, washed with ether, and dried to afford a white solid. The solid was dispersed in ether (20 mL), to which was added HCl (0.5 M, 16 mL). The mixture was stirred till it became homogeneous. The resulting solution was extracted with ether (10 mL x 3), and the organic portions were combined and concentrated to dryness in vacuo to give the pure product 16 as a white solid (198 mg, 85%).

Mechanistic Study (Control Experiments). NMR Tube Reactions
[(cod)IrCl] 2 (13.3 mg, 0.04 mmol) and 2-methylpyridine (2-MePy, 11.4 mg, 0.12 mmol) were mixed in d 8 -THF (0.5 mL) in a J. Young valve NMR tube in glovebox. The reaction was monitored by 1 H NMR at room temperature. After the solvent and excess 2-MePy were removed in vacuo, a clean 1 H NMR spectra of (cod)IrCl(2-MePy) (A) was obtained in d 8 -THF. Orange single crystals of complex A was obtained after this solution stood at room temperature for 1 day. To a n-hexane solution (10 mL) of dry pinacol (60 mg, 0.50 mmol) was added dropwise BCl 3 solution (0.75 mL, 1 M in hexane, 0.75 mmol) via syringe at 0 °C . The reaction mixture was stirred for 1 h at room temperature. The solution was condensed under vacuum to about 0.5 mL giving a S30 crude ClBpin solution. 11 The residue was dissolved in THF, which was monitored by 11 B NMR. The signal at 22 ppm corresponding to ROBpin resulted from the reaction of ClBpin with THF is in accordance with that observed in experiment (c). Figure 14. Time-dependent 11 B{ 1 H} NMR spectra of reaction (c1)
X-ray Structure Determination. All data were collected at 293K on a Bruker SMART 1000 CCD diffractometer using Mo-Kα radiation. An empirical absorption correction was applied using the SADABS program. 12 All structures were solved by direct methods and subsequent Fourier difference techniques and refined anisotropically for all non-hydrogen atoms by full-matrix least squares calculations on F 2 using the SHELXTL program package. 13 All hydrogen atoms were geometrically fixed using the riding model. Crystal data and details of data collection and structure refinements are given in Table S5.