Study On The Cyclization Of 2-Alkynylbenzaldehydes To 1-Indenones

Indenones are commonly found in pharmaceuticals and natural products with various biological activities.Indenone derivatives are synthetic precursors for many important aromatic and heterocyclic compounds.So far,many methods for the synthesis of indenones have been developed.These previously reported methods have certain limitations such as using of expensive noble metals,no readily available starting materials,poor region-selectivity,or poor functional group compatibility.Therefore,both the economic benefits and needs of indenone derivatives have driven the development of new methods for the synthesis of indenones.In this thesis,we investigated synthesis of 1-indenones through pyrrolidine-mediated cyclization of 2-alkynylbenzaldehydes.This method features very mild reaction conditions,higher atom economy and operational simplicity.The metal-free cyclization of 2-alkynylbenzaldehydes to 1-indenones was discussed.The reaction was optimized by the selection of amines,solvent and amines amount using 4-((2-formylphenyl)ethynyl)benzoate as the model substrate.Then,under the optimal conditions,a variety of indenone compounds were synthesized,and the applicability of the reaction conditions was studied.The derivatization of the indenone products were preliminarily explored,and the scale-up experiment was carried out.The reaction mechanism was studied by controlling experiments,and a possible reaction mechanism was proposed.All the new compounds were characterized by NMR,IR,melting point and HRMS.Finally,retro synthetic analysis of natural product(+)-Fumaranine and our efforts for the synthesis of(+)-Fumaranine are discribed.