Stereoselective Palladium-Catalyzed Hiyama Cross-Coupling Reaction of Tetrasubstituted gem-Difluoroalkenes
Min Li, Gavin Chit Tsui*
*Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR 999077, China,
Email: gctsui
cuhk.edu.hk
M. Li, G. C. Tsui, Org. Lett., 2024, 26, 376-379.
DOI: 10.1021/acs.orglett.3c04037
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Abstract
A diastereoselective Pd(0)-catalyzed Hiyama cross-coupling reaction of gem-difluoroalkenes provides fluoroalkenes in good yields. The use of organosilicon reagents in this reaction is advantageous over other organometallic reagents by allowing the introduction of a wide range of functional groups, including challenging alkyl groups.
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General procedure (II) for the Hiyama cross-coupling of benzyl/alkyl-substituted gem-difluoroalkenes:
To an oven-dried glass tube equipped with a stir bar was added Pd(dba)2 (5.8 mg, 0.01 mmol) and dppe (4.0 mg, 0.01 mmol). The tube was sealed with a septum, evacuated and refilled with argon three times. A solution of difluoroalkene (0.2 mmol) in 1.0 mL toluene was added under argon through syringe, followed by the addition of organosilicon reagents (0.6 mmol) and TBAF (104.6 mg, 0.4 mmol) under argon through syringe. The resulting mixture was heated at 80 °C with stirring in an oil bath for 12 h. After cooling to room temperature, the crude sample was analyzed by 19F NMR using benzotrifluoride (12 μL, 0.1 mmol) as internal standard and the E/Z ratio (>99:1) was determined. The crude mixture was extracted with CH2Cl2 (3 × 10 mL), the combined organic layers were washed with H2O (2 × 10 mL) then brine (2 × 10 mL), dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel to afford products (E/Z >99:1).
General procedure (III) for the Hiyama cross-coupling of (het)aryl-substituted gem-difluoroalkenes:
To an oven-dried glass tube equipped with a stir bar was added Pd(dba)2 (5.8 mg, 0.01 mmol) and dppe (4.0 mg, 0.01 mmol). The tube was sealed with a septum, evacuated and refilled with argon three times. A solution of difluoroalkene (0.2 mmol) in 1.0 mL toluene was added under argon through syringe, followed by the addition of organosilicon reagents (0.6 mmol) under argon through syringe. The resulting mixture was stirred at 80 °C for 12 h. The crude sample was analyzed by 19F NMR using benzotrifluoride (12 μL, 0.1 mmol) as internal standard and the E/Z ratio (>99:1) was determined. The crude mixture was extracted with CH2Cl2 (3 × 10 mL), the combined organic layers were washed with H2O (2 × 10 mL) then brine (2 × 10 mL), dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel to afford products (E/Z >99:1).
Key Words
Hiyama Coupling, fluoroalkenes, alkenylation
ID: J54-Y2024
