Facile Access to Cyclopropylboronates via Stereospecific Deborylative Cyclization: A Leaving Group-Assisted Activation of Geminal Diborons
Xin-Yi Chen, Feng-Chen Gao, Peng-Fei Ning, Yi Wei, Kai Hong*
*School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China,
Email: khong
chem.ecnu.edu.cn
X.-Y. Chen, F.-C. Gao, P.-F. Ning, Y. Wei, K. Hong, Angew. Chem. Int. Ed., 2023, 62, e202302638.
DOI: 10.1002/anie.202302638
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Abstract
A transition metal-free deborylative cyclization of geminal bis(boronates) bearing a leaving group provides cyclopropylboronates with high diastereoselectivity. When derivatives of optically active epoxides were used as the starting materials, enantioenriched cyclopropylboronates could be efficiently prepared.
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One-pot Bromination/Deborylative Cyclization
An oven-dried 10 mL vial with magnetic stir bar was charged with 2-(3,3-bis(4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl)butyl)-6-methoxypyridine (83.4 mg, 0.2 mmol) and NBP (47.5 mg, 0.21 mmol). The vial was sealed with a polypropylene open-top cap with PTFE/silicone septum, evacuated and backfilled with argon for three times, then DCM was added. The reaction mixture was then irradiated with a 3 W 455-460 nm LED lamp with cooling from circulating cold water for 2 h at 25 °C. Upon completion, the reaction mixture was concentrated in vacuo. LiOH·H2O (33.6 mg, 0.8 mmol) was added to the vial and then purged with argon for three times. THF (2 mL) was added to the mixture as solvent. The reaction mixture was stirred at room temperature for 12 h. Upon completion, the reaction mixture was passed through a silica gel plug using EA as eluent. After evaporation under reduced pressure, the crude reaction mixture was purified by column chromatography on pre-dried silica gel (PE:EA = 20:1, stain in CAM) to afford a white solid (45.7 mg, 80%, > 50:1 dr).
Stereoselective Synthesis of Enantioenriched Cyclopropylboronates
STEP I: To an oven-dried 20 mL vial equipped with a Teflon coated magnetic stir bar, 2,2'-(ethane1,1-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (0.68 g, 2.4 mmol) and anhydrous THF (5.0 mL) were added inside an argon-filled glove-box. To this solution, 2.0 M LDA (1.20 mL, 2.4 mmol) was added at 0 °C. After stirring for 20 min, (S)-2-(oxiran-2-yl)pyridine (0.24 g, 2.0 mmol, 93% ee) was added to the mixture in one portion. Then the mixture was stirred for 1 h at 0 °C. To this mixture, diphenyl chlorophosphate (0.54 mL, 2.6 mmol) was added and the reaction was warmed to room temperature and stirred for another 1 h. After the reaction was complete, the reaction mixture was passed through a silica gel plug, and rinsed with EA as eluent. After evaporation under reduced pressure, the crude reaction mixture was purified by column chromatography on silica gel (PE:EA = 5:1, stain in CAM) to afford a white solid (0.83 g, 66%).
STEP II: An oven-dried 10 mL vial with magnetic stir bar was charged with (R)-diphenyl (1-(pyridin-2-yl)-3,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl) phosphate (127.0 mg, 0.2 mmol) and LiOH·H2O (33.6 mg, 0.80 mmol). After evacuated and backfilled argon three times, DME was added via syringe. The reaction mixture was stirred at room temperature for 20 h under argon. After the reaction was complete, the reaction mixture was passed through a silica gel plug, rinsed with EA as eluent. After evaporation under reduced pressure, the crude reaction mixture was purified by column chromatography on silica gel (PE:EA = 5:1, stain in CAM) to afford a colorless oil (46.2 mg, 89%, > 50:1 dr, 93% ee, >99% es).
Key Words
ID: J06-Y2023
