Oxidative C-O/C-N Cross Coupling Of Aldehydes With Alcohols/Amines And Mechanism Study

The significance and omnipresence of carboxylic esters and amides in nature, organic chemistry, pharmaceutical chemistry, and industry has forced scientists to develop efficient methods for their preparation. Esters and amides are generally prepared via the reaction of carboxylic acid or activated derivatives with alcohols or amines. Which are not environment friendly methodology because the need for activating agent and the cost for separation of the interemediate. Instead of such two-steps operation, direct oxidative esterification (oxidative C-O cross coupling) or oxidative amidation (oxidative C-N cross coupling) of aldehydes with alcohols or amines are conceptually and economically attractive approaches and have received increasing attention. However, there are still some problems in the developed system, for instance the expensive noble metal catalysts and the demanding for excessive reagent. More importantly, there are few mechanistic studies on the oxidative coupling reactions, making it hard to understand the factors that control the efficiency. Accordingly, this thesis develops non precious cobalt catalyst system for efficient direct oxidative dehydrogenative C-O or C-N coupling of aldehydes. In addition, metal free system, which takes advantages of ionic oxidants, are developed. What’s more, detailed mechanism studies are presented.(1) Developing cobalt catalysts for the oxidative functionalization of aldehyde is a conceptually and economically attractive strategy that overcomes the need for precious metals and enables new transformations. However, challenges remin mainly because the fact that alkanols are easily transformed to the corresponding aldehydes (further to acids) or ketones through radical mechanisms, whats’s more, the subsequent P-hydrogen elimination of the hemiacetal-metal complexes to form esters might be a limitation in the case of cobalt. Herein, we disclose the first homogeneous inexpensive cobalt catalyst system for oxidative esterification of aldehydes. Where TBHP is used as oxidant and CoI2 as catalyst. AlCl3 is necessary additive to improve the selectivity of esters. And, the methods exhibit highly favorable practical characteristics:solvent free system, rather low alcohol/aldehyde ratio and the catalyst components are inexpensive and commercially available reagents. The methods are compatible with electron-poor or rich aromatic aldehydes, as well as aliphatic and heterocyclic aldehydes. Mechanism studies provide extensive insights into the cobalt mediated decomposition of TBHP in the presence of iodide ion. Investigations attribute the high efficiency to a cooperative effect between the iodide chelating ligand and cobalt ion on the catalytic cycle. The in situ generated hypoiodites (IO-/IO2-) mainly from conversion of I3- to IO3- accounts for a cooperative effect with the oxygen centered radical species to make the important hydrogen abstraction from hemiacetal intermediates more selective, thereby offering the high efficiency.(2.) A cobalt and iodide co-catalyzed oxidative C-N coupling of alcohols or aldehydes with amines is developed. The straightforward process occurrs under mild and clean reaction conditions, using T-HYDRO as the terminal oxidant and makes use of readily available starting materials. The oxidative coupling of aromatic and heterocyclic aldehydes or alcohols give products in good to excellent yields. Investigation into the reaction mechanism also find the significant influence of water on the reaction and therefore disclose potential transiency of hemiaminal and an important role of its regeneration from hydration of imines under catalysis. Mechanistic studies indicats that the in situ generated t-BuO ·/t-Bu00· rather than that iodine related IO-/IO2-/IO3- are the active hydrogen abstraction species in such catalytic process.(3) Metal-free reactions are green approaches for scientists to achieve. And the oxidative esterification of aldehydes with alcohols through radical mechanism is problematic for the existence of various side reactions. A mild, convenient and simple oxidative esterification of various aromatic aldehydes by sulfate radical redox system is presented. The reaction pathways, especially the roles of various (doubly) ionic H-bonding toward S2O82- on the reaction efficiency, are fully discussed. The expected step of converting aromatic aldehydes to acyl radical via aromatic radical cation occurrs only at the initial stage, with generating HSO4- for the oxidation process. Neither of the expected alkoxylation of acyl cation or radical cross-coupling is tenable in the formation of ester. Instead, the transiency of MeOSO3- is disclosed, which is generated from the a rate-limiting esterification between HSO4- and MeOH. The contradiction between theoretic analysis and spin-trap experiments on the origin of alkoxy radical from reaction of SRA and alkanols is well answered. More importantly, a remarkable accelerating effect of cations on both the electron transfer rate of anionic oxidant and the rate-limiting step through increased doubly ionic H-bond strength is observed. The ionic oxidant with inherent strong doubly-ionic H-bond has better performance in the oxidative esterification of aldehydes. The reaction pathways, especially the roles of various (doubly) ionic H-bonding toward S2O82- on the reaction efficiency, are fully discussed.