Design, Synthesis And Application Of Pincer Thioamide Ligands

Herein, using the strategy of reductive elimination could be facilitated by Pd(II)/Pd(IV)catalytic cycle, we designed and synthesized a new kind of pincer thioamide ligands, whichhave been detailed investigated on employing in palladium catalyzed Negishi couplingreaction, in order to solve the problem with coupling reaction involving sp3-carbon throughacclerating reductive elimination.Biphenyl-type, ferrocene-type and pincer thiourea or thioamide ligands have besuccessfully synthesized from biphenyl-2,2’-diamine, ferrocene, isophthalic acid (orpyridine-2,6-dicarboxylic acid) respectively.Pincer thioamide Pd(II) complex2a and2b was prepared from pincer thioamide ligands1a and1b, and the reaction of2a with cyclohexylzinc chloride yielded novel pincer thioimidePd(II) complex3. The structures of complexes2a,2b and3were confirmed by X-rayanalysis. Both complexes are efficient catalysts for Negishi couplings involving primary andsecondary alkyl zinc reagents bearing-hydrogen atoms. At a concentration of0.1–0.5mol%both catalysts readily promoted reactions at room temperature or even at0oC. Anexperiment on a scale of19.35g carried out at very low catalyst loading of2a (turnovernumber:6100000) highlighted the potential application of the catalytic system. Monoalkyland dialkyl zinc reagents displayed different reactivities and selectivities in reactions witharyl iodides catalyzed by complexes2a or3, and isomerization in reactions involving acyclicsecondary alkyl zinc derivatives was suppressed by using appropriate amounts of di-alkylzinc reagents. Based on preliminary kinetic profiles and reaction evidence, three possiblepathways are proposed for the reactions involving acyclic secondary alkyl zinc reagents torationalize the difference between monoalkyl and dialkyl zinc derivatives.We also found that Iron was served as the catalyst in the exploring of direct C-Hfunctionalization/C-S bond formation under mild conditions for various substrates to affordbenzothiazoles in moderate to excellent yields. Preliminary mechanistic studies revealed thatthe existence of pyridine was crucial for the high yields and selectivities. The detailedkinetic studies also indicated that the reaction was a first-order in the substrates andzero-order in oxidant Na2S2O8.