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).
Fleckenstein
Christoph A
CA
Anorganische Chemie im Zintl-Institut, TU Darmstadt, Petersenstrasse 18, 64287 Darmstadt, Germany.
Plenio
Herbert
H
D001897:Boronic Acids / Q000737:chemistry; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D011804:Quinolines / Q000737:chemistry
D001897:Boronic Acids; D006571:Heterocyclic Compounds; D011725:Pyridines; D011804:Quinolines