Palladium Catalyzes The CC Coupling Reaction To Construct Flavonoids

Flavonoids are a kind of natural products with important medicinal value.Most of the traditional methods for preparing flavonoids suffer from harsh conditions such as high temperature,long reaction time,strong basic media and tedious workup.Therefore,to develop an efficient synthetic method of flavonoid under mild conditions is highly desirable.Transition metal palladium-catalyzed carbon-carbon bond cross-coupling reaction is essential to modern organic synthesis,which reached a fairly mature level,and afforded the coupling product bearing a wide range functionality.As a general method of carbon-carbon bond formation,palladium-catalyzed reactions can efficiently assemble complex skeletons of various natural products,which is widely used in pharmaceutical chemistry,biochemistry,and materials chemistry.Based on the cross-coupling reaction of acetylated salicylic acid triazinyl ester with terminal alkyne and the carbonylative carbon-carbon bond formation of o-hydroxyiodobenzene,two kinds of reaction methods were developed for preparing flavonoids efficiently.The contents are divided as following:(1)N-methylmorpholine accelerated palladium-catalyzed cross-coupling reactions for acetyl salicylic acid triazine ester with terminal alkyne was developped.The reactions successfully flourished 24 examples of o-acetoxyacetylene ketone with satisfactory yields,up to 97%.Catalytic experiments showed that N-methylmorpholine effectively promoted the cross-coupling of steric hindered 2-acetoxybenzoic acid esters and terminal alkynes.The mechanistic expeiments found that N-methylmorpholine and triazine esters coordinate to palladium and form catalytic active species.The high-resolution mass spectrometry unveiled the possible structure of catalytic active species,indicating that N-methylmorpholine is the key to improve the catalytic activity of palladium.(2)Br(?)nsted Base was found to mediate the cyclization of o-acetoxyacetylene ketone,by which a new synthetic methodology for flavonoids was developed.This method can successfully apply for 24 examples of flavonoids with a variety of electron-containing groups and electron-withdrawing groups.The yields of the product were up to 99%.Catalytic experiments showed that the catalytic system can aviod the harsh reaction conditions,such as high temperature or strong base and by-product penta-furanone.(3)Palladium-catalyzed carbonylative Csp2-Csp coupling reaction was established,in which Fe(CO)5 was employed to replace highly toxic CO gas.The catalytic reaction of Fe(CO)5,2-iodophenol and terminal alkyne directly afford flavonoid compounds.The experimental results show that this method can be applied for substrates of aryl,alkyl,heterocyclic aromatic hydrocarbons bearing many different functional groups,which reflects the excellent efficient and group compatibility of palladium-catalyzed carbonylation reaction system.