Studies On The Synthesis Of Polysubstituted Spiro γ-lactam

The basic skeleton of cyclopropanes widely exists in a variety of natural products anddrug molecules. In addition, due to the high selective ring-opening reaction properties, thecompounds have been used as a kind of important orgaic intermediates in the synthesis ofvarious natural products, medicinal molecules, and complex molecules. In this research field,α-acetyllcyclopropanylamide compounds have both acyl and carbamoyl activating groups,which leads these compounds to high reactivity. In recent years, the synthesis of thesecompounds and the study of ring-opening reactions have attached great attention to organicchemistry and pharmaceutical chemistry.Alkynes are important intermediates, which are extensively applied on organic syntheticchemistry and pharmaceutical chemistry. During our research on synthese and applications ofvarious alkynes, we try to combine the basic structure units of cyclopropane with alkyne, anda series of polyfunctional3-hydroxypent-4-ynamides containing the cyclopropane systemwere prepared. Not only do these compounds have the basic structural features of small ringand carbon carbon triple bonds, but also they contain the nucleophilic oxygen and nitrogenatoms. Thus, these compounds may be more important intermediates in organic synthesis.Therefore, the application study on these compounds in organic chemistry and pharmaceuticalchemistry is highly desired.Given the important role of spiro γ-lactam compounds in natural products and drugmolecules and the limitation on synthesis, combining with the structural features of the3-hydroxypent-4-ynamides, polysubstitued spiro-lactam compounds were prepared throughthe intramolecular hydroamination reaction of functionalized3-hydroxypent-4-ynamides withcyclopropane system in the presence of trifluoromethanesulfonic acid in a single step. Notonly does the reaction further expand the application of3-hydroxypent-4-ynamides containingcyclopropane system in organic synthesis, but also it provides a simple, efficient and newmethod for the synthesis of multi-functionalized spiro γ-lactam.