Palladium-Catalyzed Tandem Carbonylative Diels-Alder Reaction For Construction Of Bridged Cyclic Lactones

The carbonyl-containing bridged polycyclic architectures are common structural motifs in natural products.This bridged polycyclic compound can also be used as an important intermediate for the synthesis of functionalized carbocycles,and therefore has attracted wide attention from many chemists.An effective method for the synthesis of carbonyl-containing bridged ring is the Diels-Alder cycloaddition reaction of ester group-containing cyclic dienes with alkenes.However,ester group-containing cyclic dienes usually need to be prepared through a multi-step reaction,which limits the development of this synthetic approach.Recently,our research group reported the palladium-catalyzed tandem carbonylation cycloaddition reaction of two different alkenes,which realized the one-step method to obtain bridged lactone compounds starting from acyclic substrates.Based on previous work,we developed a new carbonylation strategy using o-bromomethylbenzaldehyde and olefins as raw materials which provides a unique method for the synthesis of complex lactone-containing bridged ring compounds.We initially chosen o-bromomethylbenzaldehyde and styrene as standard substrates to proceed the reaction.Through systematic screening,we use 5 mol%PdBr2 catalyst,6.0 mol%RuPhos ligand,anhydrous sodium acetate as the base,60 atm carbon monoxide atmosphere in anisole under the temperature of 120℃ for 12 hours.Under this optimized conditions,we systematically studied the reaction properties of o-chloromethyl benzaldehyde,o-bromomethyl benzaldehyde containing various substituents,aryl alkenes,vinyl ether,vinyl amide,ethylene and simple cyclic alkenes(total of 33 alkenes).The reaction showed good functional group compatibility and substrate applicability,which can be successfully transformed into the corresponding bridged cyclic lactone compounds mainly in endo configuration with high diastereoselectivity and good yields.The reaction has good practicability and the target product can still be obtained with high selectivity through the gram-scale reaction.The functional organic molecules containing different substituents of benzocyclohexane can be obtained through simple functionalization such as ring opening reaction and selective reduction.On the basis of this research,a suitable reaction mechanism was proposed,which lays the foundation for the further development of efficient tandem carbonylation cycloaddition reaction.