Gold-catalyzed Synthesis Of α-carbonyl Group And Four, Five-membered Nitrogen Oxygen Heterocycles By Oxidation Of Alkyne

As one of the most hot topics in organic chemistry, homogeneous gold catalysishas been in-depth researched in recent years, and a lot of valuable results have beenachieved. Gold complexes are rather unique soft Lewis and π acids, which can be uesdas catalyst for the activation of C-C multibonds toward various types of reactions,such as nucleophilic reactions, oxidative coupling reactions, and propargyl esterrearrangement reactions.Many gold-mediated homogeneous catalytic reactions take place via goldcarbene intermediates. As one of metal carbene complexes, gold carbene could beobtained through the metal complex catalyzed decomposition of diazo carbene. And inmany nucleophilic reactions, gold carbenes are similar with diazo carbenes. Gold-oxo carbenoid intermediates can be generated from inter-and intramolecularoxidation of alkynes by nucleophilic oxygen-atom donor groups. In a large of reportedgold-mediated addition-elimination reactions,-oxo gold carbenoids can undergonucleophilic attack by a variety of groups, leading to cascade reactions and theconstruction of new skeletons.This thesis is concerned with studies on the synthesis of carbonyl compounds andfour-or five-membered nitrogen-and oxygen-containing heterocycles by gold-catalyzed intermolecular oxidation of terminal alkynes generated-carbonyl carbeneintermediates. It is divided into five parts as follows:（1）A general solution for the synthesis of various-acetoxy ketone has beendeveloped. This reaction uses readily available terminal alkynes as substrates andproceeds without the exclusion of moisture or air. Notably,-acetoxy ketones, ashighly valuable substrates for drug research, can be prepared in one step from alkynesin fairly good yields. Mechanistically, reactive a-oxo gold carbenes is generated asintermediates through intermolecular oxidation of alkynes and subsequentintermolecular O-H insertion with acetic acid or C-O insertion with ehtyl acetate. Thissafe and efficient generation of gold carbenes offers a potentially general entry into-oxo metal carbene chemistry without using hazardous diazo ketones. （2）Carbonyl mesylate esters are efficiently synthesized in moderate to highyields from gold-catalyzed reaction of alkynes. Mechanistically, a-oxo gold carbenesare generated as intermediates through intermolecular oxidation of alkynes andsubsequent THF ring-opening reaction. Notably, the products can be prepared in onestep from terminal alkynes as the starting material. Further more, the reaction solventwas replaced with tetrahydropyran,1,4-dioxane, or other oxygen-containingheterocyclic rings, the reactions could be carried out smoothly and obtained thecorresponding products in good yields.（3） The efficient intermolecular reaction of gold carbene intermediatesgenerated via gold-catalyzed alkyne oxidation has been realized usingN,N-dimethylformamide as both the reagent and the reaction solvent, offering agenerally efficient synthesis of1,3-diketones to achieve the C-N bond insertionreaction of-carbonyl carbene intermediates. The reaction conditions areexceptionally mild, and a range of functional groups are easily tolerated. （4）A practical and flexible synthesis of azetidin-3-ones and pyrrolidin-3-onehas been developed. The key reaction is a gold-catalyzed oxidative cyclization ofN-propargylsulfonamides. Mechanistically, a-oxo gold carbenes are generated asintermediates through intermolecular alkyne oxidation and subsequent intramolecularN-H insertion. The use of p-toluenesulfonyl as the protecting group does not influencethe reaction. Owing to the versatility of azetidin-3-ones and pyrrolidin-3-ones asimportant biologically active structures in drug research, extensive studies on theirpreparation have been well documented. Homopropargylic N-sulfonylamines aresynthesized via an efficient and simple one-pot procedure, then one step synthesis ofazetidin-3-ones and pyrrolidin-3-ones using gold catalytic oxidation ofhomopropargylic N-sulfonylamines.（5） A series of5-aryl-2-methyloxazole derivatives are synthesized viagold-catalyzed alkyne oxidation. All of the compounds have been screened for theirantiproliferative activities against MCF-7cell （human breast carcinoma）, A549cell（human lung carcinoma）and Hela cell（Human cervical carcinoma）lines in vitro.The results reveal that oxazole compounds exhibit the inhibitory activities against thecancer cell lines, and naphthalen-2-yl at C-5position of oxazole ring are the best.