A Study On The Reactions Of Alkyl 2-Acyl-1- Chlorocyclopropanecarboxylates With Different Nucleophiles

Development of specific reactions and construction of bioactive skeleton are the central focus of current research in the organic chemistry. Cyclopropane motifs were usually found in a large number of natural products and drug molecules, and its derivatives were a kind of useful three carbon synthons. The construction of various complex molecular skeletons by ring-opening reaction of cyclopropanes has attracted extensive attention of organic chemists. Cyclopropene, as a kind of special alkene containing an unsaturated double bond of its cyclic structure, has some unique reactivities owing to its strained ring tension. Up to now, the concentration of many researchers was focused on the application of 1,1-disubstituted cyclopropenes in organic synthesis. However, there were few reports about 1,2-disubstituted electron-deficient cyclopropenes generated in situ, especially for nucleophilic ring-opening reactions. In addition, the substrate structures in the reported examples are rather limited. So, it is a great demand to extend the diversity. On the basis of previous research in our lab, this dissertation explored some reactions of 2-acyl-l-chlorocyclopropanecarboxylates with different nucleophiles, and the obtained results are summarized as follows:1) Firstly, reactions of alkyl 2-acyl-l-chlorocyclopropanecarboxylates with active methylene compounds were studied in the presence of base. The results indicated that domino reactions between 1,3-dicarbonyl compounds with cyclopropene intermediates generated in situ proceeded smoothly to afford (Z)-6-hydroxyfulvene derivatives in modest to excellent yields (55-94%). Compared with common fulvenes, they possess more strong acidity and display varying spectroscopic absorption with the change of pH values. Moreover, they easily underwent the diazotization reaction to provide a new kind of azo dyes.2) Highly selective amination of 6-hydroxy fulvene derivatives with primary amines was found, especially in the presence of secondary amines. This selective amination reaction with primary amines system also occurred in the presence of a range of functional groups, giving 17 examples of amination derivatives in 39-99% yields. Moreover, a significant change in their ultraviolet and fluorescence spectra was observed when 6- hydroxy fulvene derivitives were aminated.3) Reactions of alkyl 2-acyl-l-chlorocyclopropanecarboxylates with various amines in the presence of base were explored. It was found that base-promoted domino sequence of cyclopropene intermediates generated in situ with aliphatic amines afforded 22 examples of potentially bioactive 2-pyrone derivatives in 57-97% yields under anhydrous conditions, accompanying with a spontaneously ring-opening of D-A cyclopropanes generated in situ. In addition, these 2-pyrone derivatives could emit blue fluorescene in EtOH.4) A series of alkyl 2-acyl-l-phenoxycyclopropanecarboxylates were obtained from reactions between 2-acyl-l-chlorocyclopropanecarboxylates and phenol under basic conditions. These D-A cyclopropanes smoothly underwent simple ring-opening reaction or/and cycloisomerization reaction in the presence of acid at room temperature, the product diversity greatly depending on the property of acids. Alkyl 5-arylfuran-2-carboxylates were afforded in 36-99% yields in triflic acid, whereas alkyl 2,5-dioxo-5-phenylpentanoate became the major product in other weaker protic acids and Lewis acids.5) In the presence of base, another kind of ring-opening reaction mode of 2-acyl-1-chlorocyclopropanecarboxylates with phosphite ester was observed. The reaction was initiated by nucleophilic addition of carbonyl group of phosphite, and then proceeded through umpolung reaction and ring-opening reaction to form enol phosphate ester derivatives in 18-99% yields. The similar ring-opening process of 2-acylcyclopropanecarboxylates with phosphite also well proceeded under the same conditions to yield the corresponding products in up to 94% yield.6) A novel cascade reaction between weakly nucleophilic sulfinate sodium and electron-deficient cyclopropenes derived from alkyl 2-acyl-l-chlorocyclopropanecarboxylates was developed. This methodology provides an efficient way to prepare a kind of trans-2-acyl-l-cyclopropyl sulfones in 19-89% yields with dr>20:1.