钯/氨基酸共催化环己酮分子内α-烯基化反应  

Palladium/Amino Acid Co-Catalyzed Intramolecular α?Vinylation of Cyclohexanones

作　　者：李保乐 刘人荣 梁仁校[1] 贾义霞[1] 

机构地区：[1]浙江工业大学化学工程学院,杭州310014

出　　处：《化学学报》2017年第5期448-452,共5页Acta Chimica Sinica

基　　金：国家自然科学基金(Nos.21372202;21502169及21522207)资助~~

摘　　要：利用钯/手性氨基酸共催化策略,基于烯胺中间体的Heck反应,研究了环己酮的分子内烯基化反应.在温和条件下,以中等到优良的收率合成了一系列含有氮杂双环[3.3.1]及双环[3.4.1]结构片段的化合物.并通过底物调控,实现了N-烷基取代环己酮的分子内不对称烯基化反应,获得了中等水平的对映选择性.Transition-metal-catalyzed a-vinylation of carbonyl compounds represents one of the most important car- bon-carbon bond forming approaches to the synthesis of β,γ-unsaturated ketones, which are versatile synthetic building blocks and key structural motifs appearing in biologically active molecules. For this purpose, a number of methods have been developed by utilizing palladium-catalyzed cross-coupling of vinyl halide with C--H bond a- to carbonyl group. However, the elimination of vinyl halides in the presence of strong base would afford alkynes, which remained inert and therefore re- suited in lower yields in the cross-coupling reaction. In recent years, cooperative catalysis merging transition metals and or- ganic molecules represents a powerful strategy and renders numerous efficient transformations successful. Among which, palladium/enamine catalysis has emerged as an efficient method for the direct a-functionalization of ketones or aldehydes. We therefore envisaged that a direct cross-coupling of ketones and vinyl halides in the presence of Pd（0）/amine co-catalyst; the need of weak base would avoid the formation of alkynes through elimination of vinyl halides. Herein, we report a palla- dium/chiral amino acid co-catalyzed intramolecular a-vinylation reaction of cyclohexanones, which delivers a series of bridged ring compounds under mild reaction conditions in good to excellent yields. The resulting unique bridged ring system is analogous to the important morphan scaffold （2-azabicyclo[3.3.1]nonane）, which is core structure existing in many im- portant bioactive natural products. In the meantime, asymmetric version of this reaction was also tested and a number of de- sired products were achieved in moderate enantioselectivities. A representative procedure for this reaction is as following： To a dried Schlenk tube were added compound 1 （0.2 mmol）, chiral amines （0.04 mmol, 20 mol%）, K3PO4 （0.3 mmol, 1.5 equiv.）, Pd（OAc）2 （0.01 mmol, 5 mol%） and PPh3 （0.024 mmol, 12 mol%） un

关 键 词：钯 氨基酸 烯胺 环己酮 烯基化 

分 类 号：O621.251[理学—有机化学]