Pd-Catalyzcd Construction And Modification Of Indole Skeleton Molecules

In this paper,Pd?II?/Pd?0?-catalyzed functionalization and synthesis of indole were studied by us,and two kinds of functionalizations were realized successfully.1)Pd?II?-catalyzed the oxidative esterification at indole C3 position with carboxylic acid derivative;2)Pd?0?-catalyzed tandem coupling reaction of 2-gem-dibromovinylanilines and N-tosylhydrazones to construct 2-?1-phenylvinyl?-indoles.We achieved the Csp²-H oxidative esterification of indole C3 position with carboxylic acids based on reasonable design plan and screening for the catalytic condtions for the first time,which provided a novel and convenient methodology to construct ester derivatives.We demomstrated that the mechanism of the transformation involves the following steps:Csp²-H activation,cross-coupling of indoles,ligand exchange,and reductive elimination of Pd?II?.It is noteworthy that the Csp²-H oxidative esterification of indole C3 position can be achieved after the hydrogen on the C2 position was replaced by aryl group.At the same time,we also investigated that the strategy has mild conditions,and not affected by water and oxygen;more importantly,carboxylic acids have a wide range in this reaction,this reaction is not only for liquid acids but also for solid acids,and is suitable for aliphatic and aromatic acids.In addition,we have also demonstrated that Ag₂CO₃ acts as base and oxidant in the catalytic system.Taking full advantage of the tendency of 2-bromoindole C2 position to be easily reacted,we realized a methodology that Pd?0?-catalyzed tandem coupling reaction of2-gem-dibromovinylanilines and N-tosylhydrazones to construct 2-vinylindoles.We demonstrated that the regioselectivity of the C2 alkenylation has specificity:the reaction exhibit completely Z-selectivity via the final?-H reductive elimination,and not generate products of C3 position substituent.There are excellent regioselectivity and stereoselectivity.The scope of the substrate was examined;the transformation is compatible with many different functional groups.In addition,we explored the derivatization and application of the reaction,the products of reaction could be converted into more valuable molecules via different of oxidation reactions and coupling reactions.Finally,a possible catalytic cycle was proposed and explained the reaction mechanism in detail.