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 carbon-carbon bond forming approaches to the synthesis of,β,y-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 α-to carbonyl group.However,the elimination of vinyl halides in the presence of strong base would afford alkynes,which remained inert and therefore resulted in lower yields in the cross-coupling reaction.In recent years,cooperative catalysis merging transition metals and organic molecules represents a powerful strategy and renders numerous efficient transformations successful.Among which,palladiurn/enamine catalysis has emerged as an efficient method for the direct α-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 palladium/chiral amino acid co-catalyzed intramolecular α-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 important bioactive natural products.In the meantime,asymmetric version of this reaction was also tested and a number of desired 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％) under N2,2.0 mL THF was then introduced via a syringe.The resulting mixture was stirred at 85 ℃C (oil bath) for 72 h until the reaction was complete (monitored by TLC).The solvent was then removed under vacuum and the residue was purified by flash chromatography on silica gel,eluting with ethyl acetate/petroleum ether 1 ∶ 10 (V/V) to afford the desired product.
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