Copper-Facilitated Suzuki Reactions: Application to 2-Heterocyclic Boronates

Abstract

The palladium-catalyzed Suzuki-Miyaura reaction has been utilized as one of the most powerful methods for C-C bond formation. However, Suzuki reactions of electron-deficient 2-heterocyclic boronates generally give low conversions and remain challenging. The successful copper(I) facilitated Suzuki coupling of 2-heterocyclic boronates that is broad in scope is reported. Use of this methodology affords greatly enhanced yields of these notoriously difficult couplings. Furthermore, mechanistic investigations suggest a possible role of copper in the catalytic cycle.

4‐Arylation of N‐Acylamino‐ and Aminopyrazoles by the Suzuki–Miyaura Cross‐Coupling Reaction

“…[36] Inspired by the previously reported procedures dealing with the "2-pyridyl problem", we switched to a different solvent system (DMF/iPrOH) and added 0.5 equiv. of Cu(OAc) 2 ; [37] the co-catalysis with copper allowed us to isolate biaryl 3z in a poor yield of 29 %. Similarly to the bromides 1a and 1c, the chlorides 1b and 1d proved to be eligible electrophiles for the reaction, providing the respective heterobiaryls 3b, 3e, 3h, 3j, 3m, 3o, 3w, and 3x in yields of 77-90 %.…”

Bimetallic Catalysis using Transition and Group 11 Metals: An Emerging Tool for CC Coupling and Other Reactions

“…The success of copper(I) as ligand scavenger will depend on the affinity for copper of the ligands used and the exact role played by CuX in many Stille reactions where a beneficial effect has been found, is not always clear. [87,88,91,92] In the case of Hiyama reactions, [93] or Suzuki couplings, [94] copper effects have been reported less frequently. Recently, Deng and co-workers have observed "copper effect" in Suzuki reactions, [94e] and have proposed that the reaction is operating through two pathways (Scheme 40): the basic Suzuki catalytic cycle (pathway a), and an organocopper mediated cycle which would provide a more efficient process (pathway b).…”

Synthesis of Tetra-ortho-Substituted Biaryls Using Aryltriolborates

“…By further investigations of the amounts of Pd(OAc) 2 , CuCl and BIPHEP, tetra-ortho-substituted biaryl was obtained finally in 95% yield using 5 mol% Pd(OAc) 2 /5.5 15b-c, 20, 21 The role of copper salts seem to be facilitate the transmetalation of aryltriolborates to the arylpalladium bromides by the generation of arylcopper species. 21 Under the optimized reaction conditions, hindered couplings occurred between aryltriolborates 7, 8, 9 and 11 and a number of hindered aryl bromides ( Table 2). 22 All of the ortho-substituted biaryls were obtained in excellent yields.…”