Synthesis of 1,3‐Bis‐(boryl)alkanes through Boronic Ester Induced Consecutive Double 1,2‐Migration

Abstract A general and efficient approach for the preparation of 1,3‐bis‐(boryl)alkanes is introduced. It is shown that readily generated vinylboron ate complexes react with commercially available ICH2Bpin to valuable 1,3‐bis‐(boryl)alkanes. The introduced transformation, which is experimentally easy to conduct, shows broad substrate scope and high functional‐group tolerance. Mechanistic studies reveal that the reaction does not proceed via radical intermediates. Instead, an unprecedented boronic ester induced sequential bis‐1,2‐migration cascade is suggested.


General Procedure and Characterization Data for the Products
General Procedure A: Vinyl boronic ester (0.20 mmol, 1.0 equiv.) was dissolved in diethyl ether (2.0 mL) and the alkyl/aryllithium solution (0.22 mmol, 1.1 equiv.) was added dropwise over 5 minutes at 0 °C. The solution was then stirred for 0.5 h at 0 °C, warmed to room temperature and stirred for a further 0.5 h. Subsequently, the solvent was carefully removed in vacuo and the resulting residue was taken up in acetonitrile (2.0 mL). After the addition of ICH2Bpin (0.60 mmol, 3.0 equiv.), the tube was sealed and the mixture was stirred at room temperature for 16 h. The reaction mixture was filtered through a pad of silica and rinsed with 30 mL Et2O. Flash column chromatography eluting with pentane and Et2O (pentane/Et2O = 10:1) afforded the desired product.
Caution: In order to get a good yield, the chromatography should be finished within 10 min.

General Procedure B:
To a solution of arylbromide (for 3m, 1-chloro-4-iodobenzene was used) (0.28 mmol, 1.4 equiv.) in THF (1.5 mL) at -78 °C was added a solution of n-butyllithium (1.6 M, 0.26 mmol, 1.3 equiv.) over a period of 5 minutes. The solution was then stirred for 1 h at -78 °C, at which point a solution of isopropenylboronic acid pinacol ester 1a (0.20 mmol, 1.0 equiv.) in THF (0.50 mL) was added dropwise. The solution was then stirred for 30 min at -78 °C, warmed to r.t. and stirred for a further 30 min. Subsequently, the solvent was carefully removed in vacuo and the resulting residue was taken up in acetonitrile (2.0 mL). After the addition of ICH2Bpin (0.60 mmol, 3.0 equiv.), the tube was sealed and the mixture was stirred at room temperature for 16 h.
The reaction mixture was filtered through a pad of silica and rinsed with 30 mL Et2O. Flash column chromatography eluting with pentane and Et2O (pentane/Et2O = 10:1) afforded the desired product.
Caution: In order to get a good yield, the chromatography should be finished within 10 min.
S6 General Procedure C: To a solution of arylbromide (0.28 mmol, 1.4 equiv.) in Et2O (1.5 mL) at 0 °C was added a solution of n-butyllithium (1.6 M, 0.26 mmol, 1.3 equiv.) over a period of 5 minutes. The mixture was stirred at that temperature for 1 h. After warming up to room temperature the aryllithium solution was added dropwise over 5 minutes to vinyl boronic ester (0.20 mmol, 1.0 equiv.) in diethyl ether (1.0 mL) at 0 °C. The solution was then stirred for 0.5 h at 0 °C, warmed to room temperature and stirred for a further 0.5 h. Subsequently, the solvent was carefully removed in vacuo and the resulting residue was taken up in acetonitrile (2.0 mL). After the addition of ICH2Bpin (0.60 mmol, 3.0 equiv.), the tube was sealed and the mixture was stirred at room temperature for 16 h. The reaction mixture was filtered through a pad of silica and rinsed with 30 mL Et2O. Flash column chromatography eluting with pentane and Et2O (pentane/Et2O = 10:1) afforded the desired product. Caution: In order to get a good yield, the chromatography should be finished within 10 min.
To a solution of 3r (87.2 mg, 0.2 mmol) in tetrahydrofuran (3 mL) at 0 °C was added aqueous sodium hydroxide solution (3 mL, 9 mmol, 3 M). Aqueous hydrogen peroxide solution (1.5 mL, 30 % w/w) was added dropwise. The mixture was stirred at room temperature for 4 hours. Upon the completion of the reaction as determined by TLC, the mixture was cooled to 0 °C and saturated aqueous sodium thiosulfate solution (6 mL) was added dropwise. The aqueous layer was extracted with ethyl acetate (3 x 15 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated. The product was purified by flash column chromatography on silica gel with n-pentane/ethyl acetate (5:1 to 2:1) as eluent to give the corresponding product 5 (38.9 mg, 90%) as a colorless oil.