Study On The Novel Synthesis Of Pyrazolo [5,1-?] Isoindoles And 4-acylpyrazole Derivatives

As an important class of nitrogen-containing heterocyclic compounds,pyrazoles are highly valuable in the fields of pharmaceuticals,petiscides and functional materials.As a result,the development of economic and efficient methods for the construction of the pyrazole scaffod is an important task in organic synthesis.Under this background,this thesis aims to the development of novel methods for the synthesis of pyrazolo[5,1-?]isoindoles and 4-acylpyrazole derivatives starting from readily obtainable starting materials under mild conditions.It includes the following two chapters:In the first chapter,a novel and efficient method for the construction of the pyrazolo[5,1-?] isoindole scaffold via a one-pot three-component cascade reaction of 1-(2-bromophenyl)buta-2,3-dien-1-one with hydrazine and isocyanide promoted by Pd catalyst is described.This cascade process proceeds through an initial condensation of allenic ketone with hydrazine followed by a Pd-catalyzed C-Br bond isocyanide insertion and an intramolecular C-N bond formation.When acetohydrazide was used in place of hydrazine,a more sophisticated procedure involving the initial condensation and the following C-H and C-Br bond isocyanide insertion,deacetylation,as well as C-C,C-O,and C-N bonds formation occurred to afford pyrazolo[5,1-?]isoindole-3-carboxamides with good efficiency.In the second chapter,an efficient and convenient one-pot synthesis of diversely substituted 4-acylpyrazole derivatives via copper-catalyzed cascade reactions of saturated ketones with hydrazones is reported.More strikingly,the reaction of saturated ketones with cyclic ketone hydrazones afford 4-acylpyrazoles with a functionalized side chain attached on the 3-position of the pyrazole scaffold.To our knowledge,this should be the first example in which diversely substituted 4-acylpyrazoles were efficiently prepared directly from inactivated ketones and hydrazones featured with multiple aliphatic C-H bond functionalization,C-C bond cleavage and re-organization.In summary,some novel synthetic methods for the preparation of pyrazolo[5,1-?] isoindoles and 4-acylpyrazole derivatives have been developed.Compared with literature methods,these new protocols have advantages such as cheap substrates,mild reaction conditions,broad substrates scope and good efficiency.