Nickel-Catalyzed Reductive Coupling Of Aldehydes,1,3-Dienes And Alkenyl Triflates/Alkenyl Bromides To Construct 1,4-Dienes

1,4-Dienes are very significant compounds.They not only exist widely in some active natural products,but also can be used as synthons in organic synthesis.It is known that 1,3-dienes are cheap and abundant.Therefore,using the 1,3-dienes as raw material to construct 1,4-dienes is attractive.Up to date,the hydroenylation of1,3-dienes have been well developed for preparation of 1,4-dienes,however,this method has some limitations for the construction of some structural complex 1,4-dienes.The carboalkenylation of 1,3-dienes can form two new C-C bonds at one time for synthesis of structural diverse 1,4-dinenes,but they has been underdeveloped.Most of the reported carboalkenylation of 1,3-diene need to use organometallic reagents which are sensitive to water and oxygen.In addition,organometallic reagents need to be prepared in advance,and the preparation of high functional or structurally complex organometallic reagents are relatively difficult.We know that electrophiles are both cheap and readily available.In recent years,the nickel-catalyzed reductive coupling of electrophiles have became the efficient and reliable methods to construct C-C bonds,which can successfully construct a variety of alkenes when alkenyl electrophiles are used in these catalysis.Therefore,it is interesting and attractive to develop a nickel-catalyzed reductive carboalkenylation of 1,3-dienes using alkenyl electrophilic reagents to construct 1,4-dienes.In this thesis,we have successfully realized the carboalkenylation of 1,3-dienes,using aldehydes,1,3-dienes and alkenyl trifluoromethanesulfonate/alkenyl bromide as substrates,Ni Br₂（DME）as the catalyst,2,2’:6’,2’’-terpyridine as the ligand,ⁿBu₄NI as the additive,Zn powder as the reducing agent,and DMAc as the solvent（the mixture of DMAc and THF is used as solvent for the substituted olefins）at room temperature.This reaction has the following advantages:（1）using alkenyl trifluoromethanesulfonate/alkenyl bromide instead of water-and air-sensitive organometallic reagents;（2）mild reaction conditions（the temperature of the reaction is25 ^oC）;（3）high regioselectivity and stereoselectivity（1,4-addition>>1,2-addition,and only produced the trans-1,4-dienes）;（4）braod substrate scope and good functional group tolerance,such as the aldehydes that have methoxy,tert-butyl,ester,halogen,fused ring and alkyl substitutions can be tolerated,additionally,2,6-disubstituted aldehyes,heteroaromatic aldehydes/alkenyl trifluoromethanesulfonate as well as biologically active molecules can also react smoothly to give the corresponding1,4-dienes with good yields;（5）this reaction has good chemoselectivitives（the bromide substituted aldehydes could a ord the bromide retained products in moderate yields）;（6）easy to operate and gram-scale synthesis of 1,4-dienes;（7）the products can be converted into 1,4-dienes containing multiple olefin fragments,ketones,azides and triazoles.In conclusion,we have developed a novel Ni-catalyzed three-component cross-electrophile coupling of aldehydes,1,3-dienes and alkenyl triflates or bromides employing an inexpensive commercially available catalyst and ligand（Ni Br₂（DME）and terpyridine）.This carboalkenylation of 1,3-dienes strategy enables the rapid and modular synthesis of structural diverse skipped dienes.This procotol features mild reaction conditions,good functional group tolerance,easy operation,gram-scale synthesis and excellent compatibility with complex molecules.