Research Of Gold-catalyzed Haloalkynes Hydroamination And α-oxo Gold Carbene Participation Reaction

As one of the most hot topics in organic chemistry,homogeneous gold catalysis has been in-depth researched in recent years,and a lot of valuable results have been achieved.Au(I)cation and its complexes are rather unique soft Lewis and π acids,which can be uesd as catalyst for the activation of C-C multibonds toward various types of reactions,such as nucleophilic reactions,oxidative coupling reactions,and propargyl ester rearrangement reactions.Alpha substituted ketones,such as a-alkoxyketones,a-halomethylketones,are highly versatile synthetic intermediates and building blocks in organic chemistry.Besides,they have access to the synthesis and application of the heterocyclic and asymmetric synthesis.For instance,3-pyrrolidone,2,5-disubstituted oxazole can be synthized via a-alkoxyketones.As another important spices of the alpha substituted ketones,a-halomethyl ketones have been attracting increasing attention in view of their high reactivity as a kind of synthetically important building blocks for the preparation of heterocyclic compounds of various classes including pyrroles,furans,thiophenes,imidazoles,thiazoles due to their selective transformations with different reagents.In addition,a-halomethyl ketones can involve in important transformations such as the Favorskii rearrangement reaction,Reformatsky reaction.Furthermore,the biological activity of a-halomethyl ketones as enzyme inhibitors has been described.There is no adoubt that the synthesis and applications of the alpha substituted ketones have emerged a growing focus of the organic chemists.This thesis is concerned with studies on the synthesis of carbonyl compounds by gold-catalyzed intermolecular oxidation and hydroamination of terminal alkynes.It is divided into two parts as follows:(1)A new method for the synthesis of various a-alkoxy ketones has been developed.This reaction uses readily available terminal alkynes as substrates,8-Methylquinoline N-oxide as the oxidant.Reactive a-oxo gold carbenes is generated as intermediates through intermolecular oxidation of terminal alkynes and subsequent intermolecular O-H insertion with alochol.We have examined the impact of the catalyst,oxidant and the reaction time respectively by establised a model reaction using phenylacetylene as the substate,and obtained the optimum reaction conditions.With 5 mol%Cy3PAuNTf2 catalyst,1.3 equiv of 8-methylquinoline nitrogen oxygen,and 1.1 equiv of MsOH dissolved in DCE.With terminal alkyne and alochol as raw materials,a-alkoxy ketones with various substituents are obtained via a-oxo gold carbene intermediate.Different alcohols including methanol,ethanol,isopropanol and tert-butanol are suitable solvents.(2)A general atom-economical approach for the synthesis of a-halomethyl ketones is demonstrated through hydroamination of a wide range of haloalkynes.We have examined the impact of the catalyst,solvent and the reaction tempreture respectively by establised a model reaction using phenylacetylene as the substate,and obtained the optimum reaction conditions.With 5 mol%Et3PAuNTf2,1.0 equiv o-aminophenol dissolved in DCE and react under room temperatrue for 24 hours.With haloalkynes and o-aminophenol as materials,a-halomethyl ketones with various substituents are obtained.This mild reaction bearing a wide range of functional groups could be widely applied to the organic synthesis.Other outstanding features include excellent yields from both alkyl-and aryl-substituted haloalkynes and wide functional group tolerance.It is an alternative method to conventional a-halogenation of ketones.The method broaden the scope of gold catalyzed reaction of alkynes.