Studies On Transition-metal-catalyzed Heterocyclization Of Acyclic Alkynyl Ketones

Heterocycles constitute the largest and most diverse family of organic compounds. Theyrepresent structural motifs found in a great number of biologically active natural, drugs andagrochemicals. Moreover, heterocycles are important reagents in organic synthesis which arewidely used in the synthesis of natural product and complex molecule. The synthesis ofvarious heterocycles has become an intriguing subject over the past century. Although manyapproaches for the synthesis of heterocycles and their derivatives have been reported in thepast，development of new synthetic approaches toward heterocycles, aiming at achievinggreater levels of molecular complexity and better functional group compatibilities in aconvergent and atomeconomical fashions from readily accessible starting materials and undermild reaction conditions, is one of the major research endeavors in modern synthetic organicchemistry.Transition metal-catalyzed transformations have become one of the most attractiveresearchs in modern organic synthesis chemistry due to their advantages of highregioselectivity, atom-economy and mild reaction conditions. With more and more reportspublished, transition metal-catalyzed heterocyclization of acyclic alkynyl ketones haveattracted much attention in organic synthesis in recent years. However, only a few researchesabout transition metal-catalyzed heterocyclization of acyclic acylamido alkynyl ketones havebeen reported, which severely restricted the applications of this reaction in many fields, suchas organic chemistry, natural product chemistry and pharmaceutical chemistry.With the easily available acyclic acylamido alkynyl ketones as startings, the work of thisthesis focused on the development of new synthetic methods to synthesize oxa-aza-and fusedheterocycles by transition metal-catalyzed heterocyclization reactions. There are mainly fourparts in my thesis, as highlighted below.First, a simple, highly efficient and novel gold-catalyzed heterocyclization of acyclicalkynyl ketones have been realized. We developed an approach to polyfunctionalized fusedbicyclic ketals and bridged tricyclic ketals via AuCl3-catalyzed multicomponent dominocyclization reactions of acyclic acylamido alkynyl ketones with H2O and alkanols.Second, the readily available acyclic acylamido alkynyl ketones have been used assynthetic precursors for the synthesis of a variety of multisubstituted alkoxyl-pyrrolidinonevia a novel PtI4-catalyzed intramolecular amination/intermolecular alkanolysis tandemreactions of alkyne. The reaction showed high chemical selectivity, regioselectivity and highyield.Third, an efficient synthesis of2-oxa-8-azabicyclo [4.2.1] nonane involving acyclic hydroxyl acylamido alkynyl ketones via a platinum-catalyzed intramolecular amination/alkanolysis tandem reactions of alkynes has been developed. It was the first example ofsynthesis of oxa-aza-bridged bicyclic in a single step from acyclic alkynyl ketones.At last, a base-catalyzed intramolecular carbocyanation of alkynes have been developed.This reaction involves a novel tandem intramolecular cyclization/[2+2]cycloaddition/1,3-cyano migration. It is not only a new strategy of carbocyanation but alsoprovides a facile and efficient access to different kinds of4,5-dihydropyrroles.