Research Of Gold-catalyzed Heteroatom Substituted Alkyne Hydration And A-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. Gold 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.This thesis is concerned with studies on the synthesis of carbonyl compounds by gold-catalyzed intermolecular oxidation and hydration of terminal alkynes. Besides, A series of steroid derivatives were synthesized using gold catalysis methodology for the design of biologically active steroid nucleus. It is divided into five parts as follows:(1) A general solution for the synthesis of various α-mesyloxy ketones has been developed. This reaction uses readily available terminal alkynes as substrates and proceeds without the exclusion of moisture or air. Notably, α-mesyloxy ketones, as highly valuable intermediates in organic synthesis, can be prepared in one step from alkynes in fairly good yields. Mechanistically, reactive a-oxo gold carbenes is generated as intermediates through intermolecular oxidation of alkynes and subsequent intermolecular O-H insertion with methanesulfonic acid. This safe and efficient generation of gold carbenes offers a potentially general entry into a-oxo metal carbene chemistry without using hazardous diazo ketones.(2) A new method for the synthesis of various α-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. Different alcohol, such as methanol, ethanol, isopropanol and tert-butanol are suitable solvents.(3) A general atom-economical approach for the synthesis of a-halomethylketones is demonstrated through hydration of a wide range of haloalkynes. Other outstanding features include excellent yields from both alkyl-and aryl-substituted haloalkynes and wide functional group tolerance. This protocol is an alternative to conventional a-halogenation of ketones. The method broaden the scope of gold catalyzed hydration of alkynes.(4) On the basis of acetylenic halide hydrolysis, a general, efficient and highly regioselective protocol using gold(I) complexes catalytic system for the transformation of alkynylphosphonates to the corresponding β-ketophosphonates has been successfully developed. This method produced a variety of β-ketophosphonates with the advantages of mild reaction conditions, high functional-group tolerance and excellent yields.(5) A series of17-(2’,5’-disubstituted-oxazolyl)-androsta-4,16-dien-3-one derivatives were designed and synthesized from4-androstene-3,17-dione. The structures of the target compounds were characterized by1H NMR,13C NMR, IR and HRMS. These synthesized compounds were screened for in vitro antitumor activity by MTT assay against MCF-7(human breast cancer cell line), A549(human lung cancer cell line), Bel-7402(human liver cancer cell line), Hela (human cervical cancer cell line) and PC-3M-1E8(human prostate cancer cell line). The results revealed that compounds4showed significant antitumor activities and all tested compounds displayed higher selectivity against MCF-7cell line.