Gold(Ⅰ)-Catalyzed Cascade Cycloisomerization Of Enynes

This thesis consists of two parts:1.Gold-catalyzed tandem cycloisomerization of1-ene-4,9(10)-diyne esters to tetracyclodecene and tetracycloundecene compounds with double cyclopropane unit;2.Gold-catalyzed 1,4-enyne esters to 3,5-disubstituted phenol derivatives,and meanwhile,the human luteinized hormone receptor anticoagulant(LUF5771)was obtained from one of the products.At the first part of this thesis,1-ene-4,9(10)-diynes esters were synthesized from5-hexynoic acid or 6-heptynoic acid by multi-step reaction.Subsequently,2-1a was selected as the model substrate to establish the reaction conditions.The cycloisomerization of 2-1a in the presence of[JohnphosAu(MeCN)]~+SbF6~-(5 mol%)as catalyst,100 mg 4?MS as desiccant in1,2-dichloroethane at 80 ~oC was deemed to provide the optimum reaction conditions.Under the optimum conditions,the transformation was shown to be robust with a wide variety of substitution patterns tolerated to give the two members of the carbocyclic family 2-3 in good to excellent yields and as a single regio-and diastereomer.Phenols are important core structures in a wide variety of bioactive natural products,pharmaceutical compounds and polymers as well as precursors for their construction.3,5-disubstituted phenol is one of the typical phenols,which plays an import role in drugs,natural medicines and organic materials.On the basis of the first part’s study,the second part of this thesis was to synthesize 3,5-disubstituted phenol compounds by“one-pot”method.Firstly,a variety of substituted 1,4-enyne esters were synthesized from simple aldehydes or carboxylic acids through three to four steps.Subsequently,3-1a was selected as the model substrate to establish the reaction conditions.The reaction of 3-1a in the presence of[JohnphosAu(MeCN)]~+SbF6~-(2 mol%)as catalyst and DDQ(1.2 eq)or NFSI(2 eq)as oxidant in 1,2-dichloroethane at 80 ~oC were deemed to represent the optimum conditions.Under the optimal conditions,a series of 3,5-disubstituted phenolic compounds 3-3 were constructed effectively.The synthetic versatility of the methodology was exemplified by a gram-scale reaction of one example,the ease to realize subsequent functional transformations of 3-3q,and the application of the method to the synthesis of the bioactive molecule LUF5771.