Mechanistic Insights Into The Cobalt-catalyzed Intermolecular Hydroacylation Of Aldehydes/ketones

There is an enormous application of esters in the chemical industry area such as flavours and spices,organic solvents,pharmaceuticals and advanced materials.Transition-metal catalyzed C-H activation and direct esterification received increasingly attentions as an atom economical alternative to the conventional protocols of multistep leading to esters.Up to now,the available methodologies could be categorized into the following two types:alkoxycarbonylation of C-H bonds in the presence of CO or other carboxylation reagents;hydroacylation of C=O bonds via aldehydic C-H activation.The contents of this study include:(1)Intermolecular hydroacylation of aldehydes catalyzed by an in-situ prepared low valent cobalt system was developed.The reaction conditions in terms of cobaltous salts,ligands,additives,temperature and solvents were screened and optimized;(2)Preliminary exploration of the hydroacylation of ketones was also conducted and further work related to condition optimization is underway.The highlights of this study include:The effect of the sterically hindered amine on the reaction process was disclosed by a thoroughly mechanistic study.For instance,the added iPr2NEt functions as a station of hydride transfer,which facilitates the turnover C=O insertion step through hydrogen-bonding of Co(III)-H...N.In addition,the potential effect of iPr2NEt on the induction period arising from its electron rich property was excluded by experiments.We could give conclusions as the following:The intermolecular hydroacylation went through a pathway of C-H activation,which mainly involves three steps.Firstly,the aldehydic C-H bond is activated by low-valent cobalt generated in situ to form R(CO)Co(III)-H.Secondly,hydride transfers from R(CO)Co(III)-H to aldehydic carbon of the coordinated R(CO)H with the help of basic iPr2NEt.And finally,reductive elimination of Co(III)to Co(I)gives the ester to complete the catalytic cycle of hydroacylation.