Synthesis Of Aryl Esters And Amides By Palladium-catalyzed Carbonylation Reactions

Aromatic esters and amides are prevalent in numerous pharmaceuticals and natural products,which are found to exhibit diverse pharmacological properties such as antiinflammatory,anti-tumor,and anti-viral.In recent decades,there has been significant progress in the synthesis of aromatic esters and amides.However,traditional methods still have some drawbacks such as limited substrates and harsh reaction conditions.Therefore,the development of more efficient and convenient methods to synthesize aromatic esters and amides is a research hotspot.Carbonylation reactions can efficiently and directly introduce carbonyl groups,providing an important way to access various carbonyl compounds.However,carbonylation reactions usually use toxic and flammable CO gas as the carbonyl source,which involves great safety hazards.Thus,a series of CO surrogates(such as metal carbonyl compounds,formaldehyde,chloroform,formic acid and its derivatives,etc.)have been developed.In view of the importance of aromatic esters and amides and the application value of carbonylation reactions,this thesis developed transition-metal-catalyzed carbonylation reactions to synthesize aromatic esters and amides using CO surrogates.The main contents are as follows:1.Using chromium hexacarbonyl as the CO surrogate,palladium-catalyzed double carbonylation of aryl triflates with p-benzoquinones gave various aromatic esters derivatives.This protocol could realize carbonylation of two reaction sites in one-pot method with simple reaction operation and broad substrate compatibility.2.Using benzene-1,3,5-triyl triformate(TFBen)as the CO surrogate,palladiumcatalyzed carbonylation of aryl iodides with iminoquinones gave various p-aminoaromatic esters derivatives.The mechanism experiments showed that p-aminophenol was an important intermediate in this reaction.3.Using TFBen as the CO surrogate,palladium-catalyzed carbonylation of indoles with phenols or arylboronic acids gave various carbonyl-containing indolo[2,1-a]isoquinoline derivatives.A series of indolo[2,1-a]isoquinolines were synthesized in moderate to good yields by one-pot method.4.Using molybdenum hexacarbonyl as the CO surrogate and the reducing agent,palladium-catalyzed carbonylation of indoles with nitroaromatics gave various amidecontaining indolo[2,1-a]isoquinoline derivatives.It is the first time to incorporate the amide unit into indolo[2,1-a]isoquinoline scaffolds.This reaction provides a variety of amidecontaining indolo[2,1-a]isoquinoline derivatives in moderate to good yields.Notably,this protocol could be employed in the late-stage modifications of natural products.