Christoph A. Fleckenstein

Sulfonated N-heterocyclic carbenes for Suzuki coupling in water

Sulfonated, water-soluble imidazolium and imidazolinium salts were synthesized and the respective Pd-complexes with N,N-bis(2,6-dialkyl-4-SO(3)(-)-phenyl)imidazol-2-ylidene and N,N-bis(2,6-dialkyl-4-SO(3)(-)-phenyl)-4,5-dihydroimidazol-2-ylidene ligands were applied in aqueous Suzuki coupling reactions of aryl chlorides.

Efficient Suzuki−Miyaura Coupling of (Hetero)aryl Chlorides with Thiophene- and Furanboronic Acids in Aqueous n-Butanol

An efficient Suzuki cross-coupling protocol enables the reaction of N-hetero and normal aryl chlorides with thiophene- and furanboronic acids. Coupling is effected in aqueous n-butanol as the solvent in near quantitative yield with a catalyst loading of 0.1-1 mol %. For heterocyclic substrates aqueous catalysis is found to be more efficient than Suzuki coupling under anhydrous conditions. The developed Suzuki coupling procedure utilizes biodegradable solvents and is useful for large scale reactions, as it includes the facile product separation from a biphasic solvent mixture without the need for additional organic solvents during workup.

Highly Efficient Suzuki–Miyaura Coupling of Heterocyclic Substrates through Rational Reaction Design

A dicyclohexyl(2-sulfo-9-(3-(4-sulfophenyl)propyl)-9H-fluoren-9-yl)phosphonium salt was synthesized in 64% overall yield in three steps from simple commercially available starting materials. The highly water-soluble catalyst obtained from the corresponding phosphine and [Na(2)PdCl(4)] enabled the Suzuki coupling of a broad variety of N- and S-heterocyclic substrates. Chloropyridines (-quinolines) and aryl chlorides were coupled with aryl-, pyridine- or indoleboronic acids in quantitative yields in water/n-butanol solvent mixtures in the presence of 0.005-0.05 mol % of Pd catalyst at 100 degrees C, chloropurines were quantitatively Suzuki coupled in the presence of 0.5 mol % of catalyst, and S-heterocyclic aryl chlorides and aryl- or 3-pyridylboronic acids required 0.01-0.05 mol % Pd catalyst for full conversion. The key to the high activity of the Pd-phosphine catalyst is the rational design of the reaction parameters (i.e., the presence of water in the reaction mixture, good solubility of reactants and catalyst in n-butanol/water (3:1), and the electron-rich and sterically demanding nature of the phosphine ligand).

Aqueous cross-coupling: highly efficient Suzuki–Miyaura coupling of N-heteroaryl halides and N-heteroarylboronic acids

The palladium complex of the new disulfonated 9-(3-phenylpropyl)-9′-PCy2-fluorene ligand is a highly active catalyst for aqueous Suzuki coupling reactions of N-heterocyclic chlorides and N-heterocyclic boronic acids; catalyst loadings of 0.02–0.1 mol% of Pd and two equiv. of phosphine result in the near quantitative formation of the respective coupling products at 100 °C.

Aqueous/organic cross coupling: Sustainable protocol for Sonogashira reactions of heterocycles

The water soluble Pd complex of dicyclohexyl(2-sulfo-9-(3-(4-sulfophenyl)propyl)-9H-fluoren-9-yl)phosphine was used for an efficient copper free and sustainable reaction protocol for Sonogashira cross couplings. Using a water/ipropanol mixture as the solvent and K2CO3 as base, numerous heterocyclic and aryl bromides and chlorides were reacted with various acetylenes in near quantitative yield at 1 mol% catalyst loading and 90 °C.