The number and functionality of substituents,as well as the stereochemistry of conjugated dienes,play an essential role in their synthetic utility and biological activity.This has prompted tremendous efforts aimed at ...The number and functionality of substituents,as well as the stereochemistry of conjugated dienes,play an essential role in their synthetic utility and biological activity.This has prompted tremendous efforts aimed at the stereoselective synthesis of functionalized 1,3-dienyl molecules.However,the stereoselective synthesis of multisubstituted nonterminal 1,3-dienes with heteroatom substituents remains elusive and represents a daunting synthetic challenge.We herein disclose the first palladium-catalyzed redox-neutral dienylation of internal aliphatic-substituted propargylic esters with broad nucleophiles that deliver diversely functionalized 1,2,4-trisubstituted 1,3-dienes with excellent chemo-,regio-,and stereoselectivity.The key success of this protocol lies in the nucleophilic addition to regioselectively form trisubstituted palladacyclobutene intermediate.Notably,this reaction proceeds through chemo-and stereoselectiveβ-H elimination of sterically congestedπ-allyl palladium complex to produce 1,2,4-trisubstituted 1,3-dienes.Unlike the conventional catalytic Lewis acid pathway,this redox-neutral dienylation omnipotently couples with a broad range of nucleophiles,including fluoride,phenols,alkanols,carboxylic acids,and amides.It provides a modular strategy for constructing high value-added trisubstituted 1,3-dienes with a remarkable stereoselectivity,which remains unaddressed by other methods.Numerous practical transformations of functionalized 1,3-dienes and late-stage diversifications of natural products and bioactive molecules further demonstrate the utility of this reaction.展开更多
基金provided by the National Natural Science Foundation of China(grant nos.22371125,22071111,and 22401153)the Natural Science Foundation of Jiangsu Province of China(grant nos.BK20240031 and BK20220409).
文摘The number and functionality of substituents,as well as the stereochemistry of conjugated dienes,play an essential role in their synthetic utility and biological activity.This has prompted tremendous efforts aimed at the stereoselective synthesis of functionalized 1,3-dienyl molecules.However,the stereoselective synthesis of multisubstituted nonterminal 1,3-dienes with heteroatom substituents remains elusive and represents a daunting synthetic challenge.We herein disclose the first palladium-catalyzed redox-neutral dienylation of internal aliphatic-substituted propargylic esters with broad nucleophiles that deliver diversely functionalized 1,2,4-trisubstituted 1,3-dienes with excellent chemo-,regio-,and stereoselectivity.The key success of this protocol lies in the nucleophilic addition to regioselectively form trisubstituted palladacyclobutene intermediate.Notably,this reaction proceeds through chemo-and stereoselectiveβ-H elimination of sterically congestedπ-allyl palladium complex to produce 1,2,4-trisubstituted 1,3-dienes.Unlike the conventional catalytic Lewis acid pathway,this redox-neutral dienylation omnipotently couples with a broad range of nucleophiles,including fluoride,phenols,alkanols,carboxylic acids,and amides.It provides a modular strategy for constructing high value-added trisubstituted 1,3-dienes with a remarkable stereoselectivity,which remains unaddressed by other methods.Numerous practical transformations of functionalized 1,3-dienes and late-stage diversifications of natural products and bioactive molecules further demonstrate the utility of this reaction.
