Uses
3,6-Dihydro-2H-thiaran-4-boronic acid pinacol ester is an organic intermediate that can be used in the Suzuki metal coupling reaction.
Synthesis
1. Dissolve diisopropylamine (2.5 mL, 18.1 mmol) in tetrahydrofuran (25 mL) under nitrogen protection and cool to 0°C.
2. n-Butyllithium (11 mL, 18.1 mmol, 1.6 M hexane solution) was added slowly and dropwise over 15 minutes, keeping the temperature at 0 °C.
3. cool the reaction mixture to -78 °C and add a solution of tetrahydro-thiopyran-4-one (2 g, 17.2 mmol) in tetrahydrofuran (20 mL) dropwise over 20 min.
4. the reaction mixture was stirred at -78 °C for 20 min.
5. Add N-phenylbis(trifluoromethanesulfonimide) (6.8 g, 18.9 mmol) through the powder addition funnel and rinse the funnel with tetrahydrofuran (5 mL).
6. The reaction mixture was allowed to warm slowly to room temperature and stirred overnight.
7. The reaction mixture was partitioned between ether (100 mL) and 1M aqueous sodium hydroxide (25 mL) to separate the organic layer.
8. The organic layer was washed sequentially with 1M aqueous sodium bisulfate (25 mL) and saturated brine, then dried over anhydrous sodium sulfate.
9. The organic phase was filtered and concentrated in vacuo, and the residue was purified by column chromatography on silica gel using a linear gradient elution from pure hexane to 5:1 hexane:ethyl acetate.
10. The fraction containing the target product was concentrated to afford 3,6-dihydro-2H-thiopyran-4-yl trifluoromethanesulfonate (3.5 g, 81% yield).
11. 3,6-dihydro-2H-thiopyran-4-yl trifluoromethanesulfonate (1 g, 4.0 mmol), bis(pinacol diboron) (1.1 g, 4.4 mmol) were dissolved in dimethylsulfoxide (15 mL) and nitrogen bubbled for 15 minutes to deoxygenate.
12. Potassium acetate (1.2 g, 12 mmol) and dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium dichloromethane adduct (290 mg, 0.40 mmol) were added.
13. The reaction mixture was heated to 70 °C and kept for 12 hours.
14. After cooling to room temperature, the organic layer was separated by partitioning between ether (100 mL) and water (25 mL).
15. The organic layer was washed with saturated brine (25 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuum.
16. The residue was purified by silica gel column chromatography using a 5% triethylamine/hexane pre-washed silica gel column eluting with 1:1 ether:hexane.
17. The fraction containing the target product was concentrated to afford 3,6-dihydro-2H-thiopyran-4-boronic acid pinacol ester (900 mg, 100% yield).
References
[1] Patent: WO2005/73206, 2005, A1. Location in patent: Page/Page column 14-15
[2] Patent: WO2015/89327, 2015, A1. Location in patent: Paragraph 0255
[3] Patent: US2006/30600, 2006, A1. Location in patent: Page/Page column 18
[4] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 13, p. 3544 - 3549
[5] Patent: WO2010/57121, 2010, A1. Location in patent: Page/Page column 195
