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TCI Practical Example: Three-component Reaction Using the Nickel Catalyst and DABSO

We are proud to present the synthesis of the sulfone from 4-biphenylboronic acid, DABSO and tert-butyl bromoacetate using NiBr₂(glyme) as a catalyst.

Used Chemicals

• 4-Biphenylboronic Acid [B2294]
• Nickel(II) Bromide Ethylene Glycol Dimethyl Ether Complex (= NiBr₂(glyme)) [N1298]
• 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)

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 was 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 (on silica gel, ethyl acetate:hexane = 5:95 - 15:85) to give compound 1 as a white solid (1.01 g, 76% yield).

Experimenter’s Comments

NiBr₂(glyme) and lithium tert-butoxide were weighed into a sample tube in a glove box because these reagents are moisture sensitive. When used in air, the reagents should be weighed quickly and used as soon as possible after opening.
Since the ligand of NiBr₂(glyme) can be desorbed under reduced pressure, it is desirable to complete the depressurization process as quickly as possible.
The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:4, Rf = 0.57) 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.