Investigation On Palladium-catalyzed Cascade Cyclization Of Alkenyl Ethers And Its Application

Alkenes and their derivatives are one of the most frequently used synthetic feedstocks for the building of various functionalized molecules.Compared with a large amount of research on electron-deficient alkenes,electron-rich ones receive less attention.The possible reason is the massive interactions of the transition metal with the lone pairs of electron-rich olefins,which severely limits their insertion reactivity and selectivity owing to the profound electronegativity of nitrogen as well as oxygen or sulfur atoms and the repulsion effect from its lone-pair electrons.Therefore,the transition metal-catalyzed tandem cyclization reaction involving electron-rich olefins has always been challenging.On the other hand,polyheterocyclic compounds,possessing different heterocyclic skeletons as well as rich reactive sites,usually display more excellent biological or pharmaceutical activities than single heterocycle compounds.The transition metal-catalyzed cascade cyclization reactions of alkenes and alkynes have always been the frontiers of the research and development of novel polyheterocyclic compounds.Based on the above background,we mainly studied the palladium-catalyzed cascade cyclization reaction of electron-rich olefins,and developed simple,efficient,and novel strategies for constructing potentially biologically active polyheterocyclic compounds.Besides,some biological activity tests have been conducted for these compounds.The details are as follows:(1)A novel palladium-catalyzed cascade cyclization of electron-rich alkenes with alkynyl oxime ethers for the construction of2-isoxazolyl-2,3-dihydrobenzofurans has been reported,in which the alkene ethers function as three-atom units.This method performed with mild reaction conditions,simple operations,execellent regio-and chemoselectivities and good functional tolerance,which provides a convenient and efficient method for the synthesis of polyheterocyclic compounds with novel structure and pharmaceutical research value.(2)The biological activity of 2-isoxazolyl-2,3-dihydrobenzofuran derivatives prepared by palladium-catalyzed cascade cyclization of alkenyl ethers have been investigated in detail.The prepared polyheterocyclic compounds have been tested for their proliferation inhibitory effects on a series of human tumor cell lines,such as pancreatic cancer,lung cancer,breast cancer,kidney cancer,etc.,which promoting the process of biological activity involving polyheterocyclic compounds.