Acta Chim. Sinica ›› 2017, Vol. 75 ›› Issue (5): 448-452.DOI: 10.6023/A17020080 Previous Articles     Next Articles



李保乐, 刘人荣, 梁仁校, 贾义霞   

  1. 浙江工业大学化学工程学院 杭州 310014
  • 投稿日期:2017-02-28 发布日期:2017-05-09
  • 通讯作者: 贾义霞
  • 基金资助:


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

Li Baole, Liu Renrong, Liang Renxiao, Jia Yixia   

  1. College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014
  • Received:2017-02-28 Published:2017-05-09
  • Contact: 10.6023/A17020080
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21372202, 21502169 and 21522207).

Transition-metal-catalyzed α-vinylation of carbonyl compounds represents one of the most important carbon-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 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, palladium/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 ℃ (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.

Key words: palladium, amino acid, enamine, cyclohexanone, vinylation