Pd-catalyzed direct arylation of tautomerizable heterocycles with aryl boronic acids via C-OH bond activation using phosphonium salts.
The first direct arylation via C-OH bond activation of tautomerizable heterocycles has been achieved using phosphonium salts, on the basis of a combination of the phosphonium coupling and Suzuki-Miyaura cross-coupling conditions. Optimal reaction condition is obtained through screening of phosphonium salts, Pd catalysts, and bases. The direct arylation via C-OH bond activation tolerates a variety of tautomerizable heterocycles and aryl boronic acids. The mechanism of the Pd-catalyzed phosphonium coupling is proposed to proceed via a domino seven-step process including the unprecedented heterocycle-Pd(II)-phosphonium species. Application of the Pd-catalyzed direct arylation via C-OH bond activation using PyBroP leads to the most efficient synthesis of the biologically important 6-arylpurine ribonucleoside in a single step from unactivated and unprotected inosine.
Kang
Fu-An
FA
Johnson & Johnson Pharmaceutical Research and Development, LLC, 665 Stockton Drive, Exton, Pennsylvania 19341, USA. fkang@prdus.jnj.com
Sui
Zhihua
Z
Murray
William V
WV
D001897:Boronic Acids / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006878:Hydroxides / Q000737:chemistry*; D008956:Models, Chemical; D063065:Organophosphonates / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*
D001897:Boronic Acids; D006571:Heterocyclic Compounds; D006878:Hydroxides; D063065:Organophosphonates; D010165:Palladium; D002244:Carbon