Pd-catalyzed Aminocarbonylation Of Aryl Halides:Synthesis Of Neutral/Ionic Phosphines For Production Of α-ketoamides And 1,3,4-oxadiazoles

Aminocarbonylation catalyzed by transition metal complexes is a process to build amide bonds from halogenated hydrocarbons（or unsaturated hydrocarbons）,CO and organic amines.For this process,mono carbonylation or double carbonylation could happen orientationally under the selected catalytic conditions to yield amides orα-ketoamides selectivley.In addition,due to the diversity of the involved organic amines,including N-acylhydrazides,hydrazines,amides,ureas,etc.,fine chemicals containing amide bonds with highly adding value could be synthetized via aminocarbonylation,such as N,N’-acylhydrazides,N-acylhydrazides,imides,N-acylureas,etc.Pd-complexes modified by phosphines are commonly used as catalysts for aminocarbonylation.The stereoelectronic properties of the involved phopshine play a crucial role in regulating the catalytic performance of the corresponding Pdcomplexes.Specifically,phosphine-containing hybrid ligands with hemilability exhibit unique effect on improving the performance of Pd-catalysts.Therefore,the research on design and synthesis of a series of phosphines for Pd-catalyzed aminocarbonylation is of significant importance.Herein we designed and synthesized four kinds of novel phosphines containing the same 1-（3-thienyl）-benzimidazole skeleton and applied them to Pd-catalyzed aminocarbonylation of aryl halides with different amines.The obtained results are summarized as follows.（1）Double carbonylation of aryl halides with aliphatic amines for synthesis ofα-ketoamides over phosphines modified Pd-catalystsα-Ketoamides,a unique class of amines containing adjacent carbonyl and acylamino-group in their structures,are widely applied in the fields of organic synthesis,pharmaceuticals,pesticides,etc.Double carbonylation catalyzed by Pd-complexes with involvement of phosphines is a method for one-step synthesis ofα-ketoamides from aryl halides,CO and aliphatic amines,advantageous of high atom economy,simple synthesis route and cheap available raw materials.The fulfillment of double carbonylation of aryl halides with aliphatic amines is mainly controlled by the stereoelectronic properties of involved phosphines.In this part,the novel phosphines of L1-L4 were synthesized and applied to Pd-catalyzed double carbonylation of aryl halides with aliphatic amines for synthesis ofα-ketoamides.It was found that the ionic diphosphine of L4 could serve as precursor of a hemilabile P,C（phosphine,carbene）-hybrid ligand to form a stable Pd（Ⅱ）-complex of Pd-L4.Moreover,L4-modifed PdCl₂（MeCN）₂ catalytic system exhibited good catalytic performance on double carbonylation in terms of aryl iodides conversion（81～95%）andα-ketoamides selectivity（80～91%）.The in situ FT-IR analysis revealed that PdCl₂（MeCN）₂-L4 catalytic system absolutely gave rise to the double carbonylation towardsα-ketoamides,and that the formation of double carbonylated products ofα-ketoamides was not the outcome of second-carbonylation of the mono carbonylated products of amides.In addition,the ionic diphosphine of L4involved Pd-catalytic system could be reused in the RTIL of[Bpy]BF₄（as the reaction medium instead of THF）at least for 6 runs without obvious activity loss.The leaching of Pdin the combined organic phase upon six-runs was just 0.37%（ICP-OES analysis）.（2）"Carbonylation-dehydration"tandem reaction of aryl iodides with N-acylhydrazides for one-pot synthesis of 1,3,4-oxadiazoles over phosphines modified Pd-catalysts1,3,4-Oxadiazoles,a kind of five-membered heterocyclic compounds with one O-atom and two N-atoms in the structure,are widely applied in the production of pesticides,medicine,materials,etc."Carbonylation-dehydration"tandem reaction catalyzed by Pd-complexes modified by phosphines is a method for one-pot synthesis of 1,3,4-oxadiazoles from aryl iodides,CO and N-acylhydrazides,advantageous of simple synthesis route,readily available raw materials and high tolerance of functional groups of substrates.In this part,the synthesized novel phosphines L1-L4 were applied to Pd-catalyzed"carbonylation-dehydration"tandem reaction of aryl iododes with N-acylhydrazides for one-pot synthesis of 1,3,4-oxadiazoles.L1 modified PdCl₂（MeCN）₂ catalytic system showed the best catalytic performance,leading to62～93%yields of 1,3,4-oxadiazoles.The in situ FT-IR analysis revealed that the intermediate product N,N’-acylhydrazide could be generated via the first-step carbonylation reaction of aryl iodides with N-acylhydrazides.According to the proposed reaction mechanism and ³¹P NMR characterization of phosphines,it was believed that the strong electron-donating ability and less steric hindrance of L1facilitate the coordination of weakly nucleophilic N-acylhydrazides with metal center,accounting for the best catalytic performance over L1-modified PdCl₂（MeCN）₂system.Notably,Pd-catalytic system containing the ionic diphosphine of L4 with the good stability could be recycled in RTIL of[Bmim]BF₄.