Palladium-catalyzed C-C Bond Activation Of Cyclobutanones To Construct Alkenyl And Carbonylated Indanones

Indanone is a very important compound,which is the backbone of many natural products and drug molecules.For example,donepezil is an effective market drug for the treatment of Alzheimer’s disease,and Pauciflorol F is an anti-osteoporosis agent.There are many methods for the construction of indanone,but alkenylation and direct use of CO to participate in the construction of carbonylated indanone have never been reported.In this paper,palladium catalyzed C-C bond activation of 3-(2-iodophenyl)-3-methylcyclobutan1-one to construct various alkenylated and carbonylated indanones have been reported.The main contents are as follows:1.Palladium-catalyzed the carbene insertion reaction of 3-(2-iodophenyl)-3methylcyclobutan-1-one with tosylhydrazonesThe C-C bond activation reaction of 3-(2-iodophenyl)-3-methylcyclobutan-1-one for the construction of indanone is relatively rare,and the use of tosylhydrazones to transfer carbene to construct alkenylated indanone has never been reported.In this thesis,a palladium-catalyzed C-C bond activation carbene insertion to synthesize alkenylated indanone was reported for the first time using tosylhydrazones and 3-(2-iodophenyl)-3methylcyclobutan-l-one as substrates.The choice of ligands and additives in this reaction is very important.It is necessary to choose suitable additives to inhibit the cyclopropanation reaction,and to choose suitable ligands to improve the selectivity and activity of the reaction.The reaction has the characteristics of high reaction conversion rate,mild reaction conditions and good functional group compatibility.And we made a preliminary attempt on the enantioselectivity of the reaction product,and got a higher ee value(94%ee).2.Palladium-catalyzed insertion reaction of 3-(2-iodophenyl)-3-methylcyclobutan-1-one with carbon monoxide.CO is a highly atom-economical and inexpensive C1 synthon that is common in transition metal catalysis.After the palladium-carbon bond is formed,CO insertion is a common carbonylation reaction strategy,and then the nucleophile attacks to form various carbonylation products such as amides,esters,and carboxylic acids.In this dissertation,we developed a method to directly use CO to participate in the construction of carbonylated indanones via palladium-catalyzed carbon monoxide insertion.The reaction constructs alkylpalladium species via C-C bond activation of 3-(2-iodophenyl)-3-methylcyclobutan-1one,followed by CO insertion in the balloon,and then nucleophile attack constructed carbonylated indanone.The reaction conditions are mild and have good reactivity to phenolic compounds,and a variety of esters and amides have been synthesized.