Direct Cobalt-Catalyzed Conjugate Addition of Functionalized Aryl Halides and Triflates: A New Strategy for the Conjugate Addition onto Methyl Vinyl Ketone

Abstract

An efficient cobalt-catalyzed method for the direct conjugate addition of functionalized aryl halides or triflates onto methyl vinyl ketone is described. The experimentally simple procedure relies on the use of a catalytic system consisting of CoBr₂(Bpy) and zinc and does not require the preformation of a stoichiometric organometallic species. The approach described herein displays considerable functional-group compatibility at good to excellent yields.

Key words

aryl halides - catalysis - cobalt - direct conjugate addition - methyl vinyl ketone

References and Notes

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8

Under the conditions in Table  [¹] , in the absence of water, slow formation of ArZnX was detected by GLC analysis after iodolysis. In presence of water, no ArZnX is observable.

10

General Procedure for Conjugate Addition of Aryl Halides or Triflates onto MVK A flask was charged with aryl halide or triflate (7.5 mmol), LiBr (7.5 mmol, 651 mg), zinc powder (15 mmol, 981 mg), DMF (9 mL), and pyridine (2 mL). A solution of CoBr₂ (20 mol%, 1.5 mmol, 328 mg), 2,2′-bipyridine (20 mol%, 1.5 mmol, 234 mg), MVK (1.1 equiv, 8 mmol) and H₂O (0.5 equiv, 3.75 mmol, 68 µL) in DMF (10 mL), first stirred at r.t. for 10 min, was added dropwise to the resulting solution (ArX, LiBr, Zn in DMF-pyridine) stirred at 80 ˚C or 110 ˚C. After addition, the amount of the corresponding coupling product was measured by GC using an internal reference (dodecane, 200 µL). The reaction mixture was poured into a soln of 2 N HCl and extracted with Et₂O or CH₂Cl₂. The organic layer was washed with a sat. soln of NaCl and dried over MgSO₄. Evaporation of solvent and purification by column chromatography on SiO₂ (pentane- Et₂O) afforded the conjugate adducts characterized by NMR (^¹H, ^¹³C, ^¹9F) and mass spectrometry.