Palladium-Catalyzed Tandem Arylation/Allylsubstitution And Cycloaddition Reactions Of 2,3-Allenol

Due to the important role of allyl compounds in organic synthesis and natural products,the conversion of easily available raw materials into allyl derivatives is an important research topic in modern organic synthesis.The three-component tandem arylation allylation reaction of terminal diene compounds with aryl iodides and nucleophiles has been loved by the majority of researchers because of its The raw materials are easy to obtain and can form two chemical bonds in one pot operation.However,in the three-component tandem reactions that have been reported so far,most of the obtained are linear allylated derivatives,and there are only a few reports on branched allylic products,and there is no asymmetry in the reaction.Catalytic research.Therefore,this type of reaction faces two challenges.The first is how to control the regioselectivity of the three-component tandem reaction to obtain branched allyl derivatives;the second is how to achieve asymmetric catalysis of this type of reaction to obtain the hand Sexual allylation products.In this paper,2,3-allenol is used as a raw material to develop a new method for synthesizing functionalized allyl products,which can effectively control its regioselectivity to obtain branched allyl products,and The product has excellent enantioselectivity.The main research work is as follows:1.Study on the three-component arylation etherification reactionUsing 2,3-allenol,aryl halides and various alcohol compounds as substrates,a new three-component tandem arylation etherification method was developed.The method utilizes the synergistic catalysis of a palladium complex and an organoboron reagent to realize the regioselectivity control of the three-component tandem reaction.Through a series of optimization of conditions,the arylated allyl etherification product was successfully obtained with good yield and excellent regioselectivity.The functionalization of the drug molecule and the preparation of the dihydrofuran product proved the synthetic utility of the method.At the same time,technological amplification of the catalytic reaction can also obtain the target product with better yield and regioselectivity.2.Study on the three-component arylation amination reactionThrough the reaction of allenol with aryl halide and 2-pyridone,a new catalytic method for the synthesis of chiral N-substituted 2-pyridone derivatives was successfully developed.This method is the first report of asymmetric catalysis of the three-component tandem reaction of related olefins so far.In this reaction system,by using Pd₂(dba)₃·CHCl₃ and(S,S,S)-SKP in-situ generated palladium complexes as catalysts,the carbon-carbon bond and Construction of carbon-nitrogen bond.The universality of this reaction method was investigated using different substituted aryl iodides and 2-pyridone,and various functionalized N-allyl substituted 2-pyridines were successfully obtained with good yield.Ketone compounds,and it has good regioselectivity and excellent enantioselectivity.Control experiments show that the hydroxyl groups on the dienol are essential for the control of the reactivity and branching selectivity of the method.Combining controlled experiments,spectroscopy studies of related active substances,and Hammett analysis of the process,the reaction mechanism was clarified.The gram-level reaction and product conversion prove the synthetic utility of the method of the present invention.3.Study on the three-component tandem arylation allyl cyclization reactionThe first example of a palladium-catalyzed three-component asymmetric tandem arylation allyl cyclization reaction was successfully achieved using allenol,aryl iodides and Michael acceptors as substrate pairs.This reaction method provides a new idea for the synthesis of tetrahydrofuran derivatives with multiple chiral centers.In the reaction process,Pd₂(dba)₃·CHCl₃ and palladium complexes generated in situ by bisphosphine ligands were used as catalysts,and multifunctional tetrahydrofurans containing different substitutions were obtained in a one-pot method with high yield Compound,and its product has very good enantioselectivity.With this method as a key step,a natural product with stereoselectivity can be successfully obtained through fewer steps and a higher yield,which provides a new simple and effective method for the synthesis of such natural products.