Copper-Catalyzed Asymmetric Vinylogous/Bivinylogous Propargylic Substitution Of Enol Silyl Ethers To Synthesize 1,5-Enynes Esters

α,β-unsaturated carbonyl compounds refer to amides,ketones,esters and other types of compounds containing α,β-unsaturated double bonds,which are widely used in organic synthesis.Because the electron-deficient olefin has high reactivity,it can participate in many types of reactions such as Michael addition reactions,Diels-Alder reactions,cycloaddition reactions and dihydroxylation reactions.The enantioselective synthesis of δ-substituted α,β-unsaturated carbonyl compounds is a challenging task in synthetic chemistry.Therefore,the development of new synthetic methods for synthesis of such chiral compounds has very important application value and theoretical significance.Herein,we use a new type of bipyridyl P,N,N-ligand and crotonate-derived dienol silyl ethers as carbon nucleophile to participate in the asymmetric vinylogous propargylic substitution reactions,achieving the copper-catalyzed synthesis of 1,5-enynes esters with highly regioselectivity and stereoselectivity.Copper-Catalyzed Asymmetric Vinylogous/Bivinylogous Propargylic Substitution of Enol Silyl Ethers to Synthesize 1,5-Enynes Esters.The α,β-unsaturated carbonyl compounds with 8-substituted chiral centers have a wide range of applications in the field of drug synthesis and organic synthesis.For example,compounds containing y-butene lactone/lactam structure have excellent performance in antibacterial,antiviral and inhibiting cancer cells,at the same time,it contains the Michael acceptor structural unit,which provides opportunities to realize the intramolecular or intermolecular cycloaddition reactions.When there are other active functional groups in the molecule,such as alkynes,it is easy to achieve intramolecular cylcosiomerization of enyne and olefin metathesis or other ways.However,in the reported methods of α,β-unsaturated carbonyl compounds withδ-substituted chiral centers,there are problems such as complex catalytic systems,poor regioselectivities,limited substrate scopes,or expensive metal catalysis.Therefore,the development of earth-abundant metal asymmetric catalysis to construct such chiral frameworks has very important research significance.As a highly active carbon nucleophile,the crotonate-derived dienol silyl ether has been widely used in various asymmetric vinylogous reactions.It can be regarded as the equivalent of 1,3-dienol anion,both the α-site and β-site have nucleophilicity in the reaction with electrophiles,thus controlling the regioselectivity of the reaction is very challenging.As a common reagent for asymmetric propargylic substitution(APS)reaction,propargylic alcohol ester,it is easy to form an electrophilic allenylidene metal intermediate(Cu-allenylidene)under the copper catalyst system,which is easily attacked by different kinds of nucleophiles(C,N,O).Herein,we developed an asymmetric vinylogous propargylic substitution of various types of enol silyl ethers with propargylic alcohol esters catalyzd by CuCl with chiral bipyridyl P,N,N-ligand.Variety of chiral 1,5-enynes esters were synthesized with the highest yield of 98%and a regioselectivity ratio of 3:4>20:1 and up to 97%ee(Scheme 1).Mild reaction conditions,a wide substrates scope and good functional group tolerance.It solves the problem of regioselectivity in the substrate reaction while maintaining good to excellent enantioselectivity with excellent yield.The development of this synthetic method not only expands the new method of asymmetric synthesis of δ-substituted α,β-unsaturated carbonyl compounds,but also advances the research of asymmetric propargylic substitution reactions involving carbon nucleophiles.