Bis(sulfur Dioxide)-1,4-diazabicyclo[2.2.2]octane Adduct

Used Chemicals

• 4-Biphenylboronic Acid (contains varying amounts of Anhydride) [B2294]
• Nickel(II) Bromide Ethylene Glycol Dimethyl Ether Complex (=NiBr₂(glyme)) [N1050]
• 3,4,7,8-Tetramethyl-1,10-phenanthroline (= tmphen) [T0847]
• Bis(sulfur Dioxide)-1,4-diazabicyclo[2.2.2]octane Adduct (= DABSO) [B3960]
• Lithium tert-Butoxide (= LiOtBu)
• tert-Butyl Bromoacetate [B1473]
• 1,3-Dimethyl-2-imidazolidinone (= DMI) [D1477]

Procedure

Under nitrogen atmosphere, a degassed DMI (20 mL) solution of 4-biphenylboronic acid (792 mg, 4.00 mmol), DABSO (577 mg, 2.40 mmol), tmphen (95 mg, 0.40 mmol), lithium tert-butoxide (320 mg, 4.00 mmol) and NiBr₂(glyme) (123 mg, 0.40 mmol) was stirred at 100 °C for 14 hours. The mixture was cooled to room temperature and tert-butyl bromoacetate (1.17 mL, 8.00 mmol) was added and the reaction mixture stirred for 1 hour. Water (20 mL) was poured into the reaction mixture and the mixture was extracted with diethyl ether (50 mL x 3). The combined organic phase was washed with water (50 mL) and brine (40 mL), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by medium pressure preparative chromatography (ethyl acetate:hexane = 5:95 - 15:85 on silica gel) to give compound 1 as a white solid (1.01 g, 76%).

Experimenter’s Comments

NiBr₂(glyme) and LiOtBu were weighed into a sample tube in a glove box because these reagents are moisture sensitive. If these were used in air, it should be weighted quickly and used up the reagents as soon as possible after opening.
Since the ligand of NiBr₂(glyme) may be desorbed under reduced pressure, depressurization operations is desirable to be finished as soon as possible.
The reaction mixture was monitored by TLC (ethyl acetate:hexane = 2:1, Rf = 0.38) and UPLC-MS.

Analytical Data

Compound 1

¹H NMR (400 MHz, CDCl₃); δ 8.00 (d, 2H, J = 8.9 Hz), 7.78 (m, 2H), 7.58–7.66 (m, 2H), 7.42-7.54 (m, 3H), 4.08 (s, 2H), 1.58 (s, 2H), 1.39 (s, 9H).

Lead Reference

• Nickel(II)-Catalyzed Synthesis of Sulfinates from Aryl and Heteroaryl Boronic Acids and the Sulfur Dioxide Surrogate DABSO
• P. K. T. Lo, Y. Chen, M. C. Willis, ACS Catal. 2019, 9, 10668.

Used Chemicals

• 4-Bromobiphenyl [B1330]
• Bis(sulfur Dioxide)-1,4-diazabicyclo[2.2.2]octane Adduct (= DABSO) [B3960]
• Bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (= PdCl₂(Amphos)₂ [B6255]
• Triethylamine (=Et₃N) [T0424]
• N-Fluorobenzenesulfonimide (=NFSI) [F0335]
• Isopropyl Alcohol (= IPA)

Procedure

To a solution of 4-bromobiphenyl (1.17 g, 5.00 mmol), DABSO (721 mg, 3.00 mmol), and PdCl₂(Amphos)₂ (177 mg, 0.25 mmol) in anhydrous isopropyl alcohol (20 mL) was added triethylamine (2.1 mL, 15 mmol) at room temperature and the mixture was stirred at 75 °C for 23 hours. The suspension was cooled at room temperature and NFSI (2.36 g, 7.5 mmol) was added and the reaction mixture stirred for 3 hours until completion. The solvent was removed under reduced pressure. The residue was diluted with ethyl acetate (20 mL) and filtrated through celite pad. The filtrate was washed with saturated aqueous Na₂S₂O₃ solution (20 mL) and brine (20 mL), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by medium pressure preparative chromatography (ethyl acetate:hexane = 2:98 - 5:95 on silica gel) to give compound 1 as a white solid (928 mg, 79%).

Experimenter’s Comments

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:9, Rf = 0.57) and UPLC-MS.

Analytical Data

Compound 1

¹H NMR (400 MHz, CDCl₃); δ 8.12–8.04 (m, 2H), 7.86–7.80 (m, 2H), 7.67–7.58 (m, 2H), 7.44-7.55 (m, 3H).

Lead Reference

• One-pot palladium-catalyzed synthesis of sulfonyl fluorides from aryl bromides
• A. T. Davies, J. M. Curto, S. W. Bagley, M. C. Willis, Chem. Sci. 2017, 8, 1233.

Reference

• Copper(I)-catalyzed Sulfonylative Suzuki?Miyaura Cross-coupling
  • Y. Chen, M. C. Willis, Chem. Sci. 2017, 3249.

Reference

• DABCO- Bis (sulfur dioxide), DABSO, as a Convenient Source of Sulfur Dioxide for Organic Synthesis: Utility in Sulfonamide and Sulfamide Preparations
  • H. Woolven, C. Gonzalez-Rodriguez, I. Marco, A. L. Thompson, M. C. Willis, Org. Lett. 2011, 13, 4876.

Reference

• Synthesis of Aromatic Sulfones from SO₂ and Organosilanes Under Metal-free Conditions
  • N. von Wolff, J. Char, X. Frogneux, T. Cantat, Angew. Chem. Int. Ed. 2017, 56, 5616.