A Number Of Three-component Tandem Reaction

The development of new reactions and approaches of Organic Chemistry has all along been one of the major tasks for the organic chemists nowadays.In this dissertation,we have focused our efforts on the design and systematical research on four categories of multi-component cascade reaction based on imine and benzyne. The details and results are summarized below:(1)An ABC style three component cascade reaction of aromatic aldehydes, aromatic amines and diethyl malonic ester or cyclohexanone has been developed.This Mannich-type reaction affordedβ-amino carbonyl compounds in a mild condition. The reaction was also applied for the liquid-phase synthesis ofβ-amino carbonyl compound library using soluble PEG as a support.Using 1 mol%Zn(OTf)₂ as the catalyst,this efficient method provided a 43-member library ofβ-amino carbonyl compounds with yields 45～98%.(2)An ABC style cascade reaction of 2-azido-3-arylacrylates,2-diazones and triphenylphosphine to isoquinolines and benzoisoquinolines has been developed.A plausible mechanism for this approach has been proposed as follows.First, 2-azido-3-arylacrylate reacts with triphenylphosphine to form phosphazene,while 2-diazone transforms to ketene through a Wolff rearrangement.Then the aza-Wittig reaction between phosphazene and ketene affords N-vinylic ketenemine.Finally,the electrocyclic ring-closure of N-vinylic ketenemine and a subsequent tautomerization lead to the formation of isoquinolines or benzoisoquinolines.Without any metal-catalyst,this approach provided a 29-member library of isoquinolines and benzoisoquinolines with yields 60～92%.(3)An AAB style cascade reaction of aryl azides and aryloxyacetyl chlorides has been developed.When 2 equiv of aryl azides was used,only N,N'-diarylamidines was obtained.This simple and efficient one-pot synthesis yielded a 17-member library of N,N'-diarylamidines with yields 70～85%.We have proposed a tentative mechanism on the basis of the deuterium-labeling experiments.(4)An AAB style cascade reaction of benzyne and 1,3-diones has been developed.Catalyzed by 5%mol CuBr and 5%mol CCl₃COOH,this reaction afforded 2,2-diphenyl-1,3-diones.A plausible mechanism has been illustrated for the construction of this class of quarternary stereocenters.The tandem process involves two nucleophilic additions of enol of 1,3-dione to the in situ generated benzyne. Copper salt and organic acid CCl₃COOH could promote the formation of enol and hence catalyze the cascade reaction.This novel and general method for the 2,2-diphenyl-1,3-diones provided a 21-member library of 2.2-diphenyl-1,3-diones with yields 60～90%.