A Study On The Cascade Reaction Of Acylhydrazones And Alkyl 2-Aroyl-1-chlorocyclopropanecarboxylates

Acylhydrazones derived from aldehyde or ketones which acts as an common 1,3-diplor were employed to the cycloaddition reaction with alkene to give pyrazolidines or pyrazoles under the catalysis of lewis acid. Pyrazolidines and pyrroles were widely existed in nature as for its important application in the field of pharmaceuticals, biologies and materials. Furthermore, they also act as valuable precursors designed for the synthsis of natural products and biologically important molecules. In view of these, effective construction of these compounds becomes a meaningful study in organic chemistry. In addition, in those work, considerable efforts were devoted to the development of efficient acidic catalysts that can activate the acylhydrazones efficiently. To our knowledge, few examples referred to basic catalyzed the reaction of acylhydrazones were reported up to now. We carry out the study of the cascade reaction between acylhydrazones and reactive cyclopropene intermediate bearing two withdrawing groups on its C=C bond developed in our lab. The detail studies are as follows:(1) We first explored the reaction of 2-acyl-1-chlorocyclopropanescarboxilic esters with benzoylhydrazones in the presence of base, and the result showed that solvents and temperature have a great influence on the reaction. The formal nucleophilic addition product was obtained in high yield(up to 85%) and excellent diastereoselectives(>25:1) when the reaction was conducted in THF at 50 oC.(2) While a cascade reaction was occurred to afford the potential bioactive multi-substituted pyrazolidines with two separated isomers on column in high yields and moderate dr values when the reaction was carried out in presence of base in DMSO at room temperature. The two isomers were individually confirmed by NOE and X-ary analysis. In addition, we found that such bicyclic pyrazolidines could complete converted to 2,3,5-trisubstituted pyrroles in high yield(up to 99 %) by treating with acid-base cocatalysis.(3) Reactions between the 2-acyl-1-chlorocyclopropanescarboxilic esters and acylhydrazono esters derived from ethyl glyoxalate or ketoaldehyde in the presence of base have been disclosed. The result showed that a 2,3,5-multifunctionalized pyrrole can be obtained directly under basic conditions. Scope of the corresponding domino reaction was explored under the optimal conditions which were determined after screening of bases, temperature, and solvents. Various kinds of pyrroles were obtained in high yield(up to 93 %). Furthermore, we have proposed the corresponding reaction mechanism in detail.