Copper Catalyzed Perfect Stereoselective Cis-hydrogenation Of Alkynes

cis-Alkene structure widely exists in biologically impotant natural and synthetic organic compounds.The stereoselective semihydrogenation of internal alkynes is the simplest and most straightforward approach to achieve cis-alkenes,and both heterogeneous and homogeneous catalytic methods have been developed to obtain the desired products.However,partial isomerization of the cis-alkene to the trans-alkene,double-bond shifts and over-reduction to the alkane are notable issues in those catalytic systems.Copper hydride catalyzed 1,4-and 1,2-reductions of carbonyl compounds had attracted much attention because of the mild reaction condition,high regio-and stereoselectivity.Meanwhile,the reactivity of copper hydride with unsaturated carbonecarbon bonds had been observed in its reaction with terminal alkynes,internal alkynes,and olefins conjugated with aromatic groups.Ryo et al.also reported the copper hydride-mediated stereoselective reduction of alkynes activated by electronattracting sulfonyl groups.All of the copper species that mediate the semihydrogenation of internal alkynes show nearly perfect cis-selectivity.Recently,significant progress has been made in the copper catalyzed semihydrogenation of alkynes.Tsuji and Lalic reported a bisphosphine and NHC coordinated copper catalyst,respectively.However,Tsuji's method utilized different ligands and reaction conditions for different type substrates,which bring difficult choice in application.The IPrCuO-t-Bu catalyst,reported by Lalic,is air-unstable,which limits its wide application.Therefore a more general method is still desired.This paper mainly studies the optimization of reaction conditions,the scope of the substrates,the synthesis application and mechanism of speculation about copper-catalyzed Z-selective semihydrogenation of alkynes.(1)The optimization of reaction conditions including:copper salt,ligands,solvents,alkali,reducing agent,etc.We first used 4-decyne as a model substrate.The present study shows that a copper catalyst can generate in situ from air-stable and widely available Cu(OAc)2·H2O(0.05 equiv)and IPr HCl(0.05 equiv)in the presence of t-BuOK(0.1 equiv).Gas chromatography rate is 100%in 20 h at 50?with reducing agent PMHS.No E-alkene and overreduction products were observed by 1HNMR.(2)The scope of substrates including:hydroxyl,nitrocellulose,halogenated and amino types of functional groups alkyne.These types of substrates are applicable and can be used in a large number of synthetic preparation.The Z/E ratios of the obtained alkenes were generally>99%,and that semireduction of bulky alkynes also went smoothly.(3)We designed and synthesized the precursor of combretastatin A-4 and cis-combretastain can generate with a yield of 70%under standard reaction conditions.(4)We had proposed the reasonable mechanism.Alkenyl copper is the key intermediate,which was formed from the cis-addition of copper hydride to alkyne substrate.Alkenyl copper was protonated by the alcohol to form the desired product.The hydrosilylation step had been excluded base on two experimental facts.