Synthesis Of Coumarin Derivatives Through Cascade 1,4-conjugate Addition/Intramolecular Annulation Of Propargylamines

Coumarin scaffolds are abundantly found in many natural products,biologically active intermediates and functional material molecules,and constitute as one of the most important structural motifs for developing new pharmaceuticals.In addition,ohydroxyphenyl propargylamines(o-HPPAs)are useful organic synthetic intermediates which is are easily to prepare,stably and have multiple reactive sites.Recently,oHPPAs have been widely applicated in organic synthesis for the construction of the Oheterocyclic skeleton via cascade 1,4-conjugate addition and subsequent intramolecular annulation of nucleophiles to alkynyl ortho-quinone methides(o-AQMs),which in situ generated from modular propargylamines under bases,Lewis acids or thermal conditions.In this thesis,the progress of the synthetic methodologies of coumarin derivatives has been firstly reviewed.Furthermore,a novel and efficient strategy for the synthesis of benzo[c]chromen-6-ones and functionalized chroman-2-ones has been developed through the cascade reactions of o-HPPAs with dimethyl 3-oxoglutarate and ethyl-amino-3-arylacrylates.The detail research contents are as follows:Part Ⅰ:A DBU-mediated cascade strategy of o-AQMs(in situ generated from modular propargylamines)with dimethyl 3-oxoglutarate for constructing hydroxylated/arene-functionalized benzo[c]chromen-6-one core has been achieved.This cascade process presumably involves a sequence of 1,4-conjugate addition,followed by the lactonization,alkyne-allene isomerization,enol-keto tautomerization,6π-electrocyclization,and aromatization.This protocol features mild reaction conditions,simple operation,rich structural diversity and good functional group tolerance.It is notable that the halo moiety,e.g.,-Cl and-Br.located at either the phenolic or alkynyl arene rings,remained intact.In order to demonstrate the utility of the obtanied products.Product 3aa was then converted to its Tf analogue 8.Subsequent Pd-catalyzed Sonogashira coupling reactions generated the biologically active alkynylated products.A photophysical survey reveals that the benzo[c]chromen-6-one products exhibit fluorescence properties,and show potential for exploring fluorescent material applications.Part Ⅱ:Using ethyl-3-amino-3-arylacrylates as nucleophile,a ZnI2-promoted one-pot cascade reaction of in situ generated o-quinone methides(oQMs)with ethyl-3-amino-3-arylacrylates for the synthesis of methylenechroman-2ones has been developed-This process proceeds via a sequence of 1,4-conjugate addition,followed by the intramolecular transesterification process.A series of 4alkynyl,4-alkenyl and 4-aryl methylenechroman-2-one derivatives were obtained with excellent functional groups tolerance under the standard conditions.Particularly noteworthy is that the-Br and-Cl groups remained intact during the course of the reaction,thus,this protocol is complementary to the inherent shortcomings of the existing transition-metal-catalyzed coupling reactions.Furthermore,a series of novel chromeno[3,4-c]pyrrol-4(2H)-ones were obtained using the propargylamines bearing with the electron-withdrawing groups on the phenyl ring under the standard conditions through the cascade 1,4-conguate addition and subsequent two ring-closure steps process.In summary,a novel and efficient strategy for the formation of modular assembly of hydroxylated/arene-functionalized benzo[c]chromen-6-ones and functionalized 3methylenechroman-2-one derivatives has been developed by using o-HPPAs as the precursors of the active o-quinone methides(o-QMs).The protocols feature broad substrate scope,good functional group tolerance,mild reaction conditions,simple operation,and rich structural diversity,and provide a new strategy for the application of o-HPPAs in organic synthesis and the construction of coumarin skeleton.