The Application Of Phosphorous Oxide In Suzuki Reaction And Synthesis Of α-ketoamide Under Metal-free Condition

During the past half of century, the development of efficient and selectivecatalytic reactions for C-C bond formation has been a significant focus of organicchemistry. The palladium-catalyzed Suzuki coupling reaction with aryl halides andarylboronic acid is one of the most widely employed transition metal catalystreactions. Electron-rich, sterically hindered phosphine ligands are one of the mostimportant ligands for Palladium catalyzed cross-coupling reactions. In this work, Anovel diaminophosphine oxide (L1and L2) was synthesized and applied as ligand inpalladium-catalyzed Suzuki couplings reaction of aryl bromides and chlorides.With L1and L2in hand, we first tested their catalytic activity with a variety ofsolvents, bases, temperature and ligands and Pd2(dba)3for Suzuki reaction usingphenylbromide and phenylboronic acid as substrates. WhentBuOK was used asbase, L1as ligand, the yield of coupling product was improved to94%in THF under70℃.Under the optimized reaction conditions, the coupling reactions between a lotof aryl bromides and some arylboronic acids were carried out and the results weresummarized. Both electron-rich and electron-deficient aryl bromides wereefficiently coupled with arylboronic acids to give biaryl products(1–12) in excellentyields (76–96%).a-Ketoamides are key units of many natural products, biological compounds andpharmaceuticals. They have been widely developed to design inhibitors of peptidases,histone deacetylases, human cytosolic phospholipase and HIV proteases. Because oftheir important biological properties in the field of medicinal chemistry, a lot ofsynthetic routes have been developed.Among these methods for the synthesis of a-ketoamides, amidation of Ketone orAldehyde with amines catalyzed by transition-metal have been widely used. Herein,we present an Bu4NI-catalyzed radical oxidative coupling of readily available arylmethyl ketones with dialkylformamides using TBHP(tert-Butylhydroperoxide) asoxidant to access a-ketoamides in water. This method offers a new, green andmetal-free approach to a-ketoamides. We chose p-chloroacetophenone and DMF asmodel substrates using variety of oxidizer and catalyst to optimize the reactionconditions. When Bu4NI and TBHP was exist at the same time, the result of the reaction was found to be the most effective under100℃. The novel radical oxidativeamidation protocol was extended to different aryl methyl ketones anddialkylformamides under the optimized conditions and20different of a-ketoamideswere synthesized.All of compounds synthesized were characterized by1H NMR,13C NMR,31PNMR and MS.