Acta Chimica Sinica ›› 2014, Vol. 72 ›› Issue (7): 841-844.DOI: 10.6023/A14040334 Previous Articles     Next Articles

Special Issue: 不对称催化与合成



孙利辉, 梁志钦, 叶松   

  1. 北京分子科学国家实验室 中国科学院分子识别与功能重点实验室 中国科学院化学研究所 北京 100190
  • 投稿日期:2014-04-28 发布日期:2014-06-27
  • 通讯作者: 叶松
  • 基金资助:


Asymmetric N-Heterocyclic Carbene-catalyzed [4+2] Cycloaddition of Ketenes with α-cyanochalcones

Sun Lihui, Liang Zhiqin, Ye Song   

  1. Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190
  • Received:2014-04-28 Published:2014-06-27
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21272237).

The N-heterocyclic carbene (NHC)-catalyzed enantioselective cycloaddition reactions of ketenes are powerful methods for the synthesis of chiral heterocycles. Followed by the previous reported NHC-catalyzed [2+2] and [4+2] cycloaddtion of ketenes with imines, ketones and various heterodienes, the NHC-catalyzed enantioselective [4+2] cycloaddition of ketenes with α-cyanochalcones was investigated in this paper. In the presence of the bulky N-heterocyclic carbene derived from L-pyrogutamic acid, the reaction of ketenes with α-cyanochalcones went smoothly, giving the corresponding chiral multisubstituted dihydropyranones in good yields with good diastereoselectivities and high enantioselectivities. Initially, several NHCs derived from L-pyrogultamic acids were screened for the reaction. The NHC 4b with bulkyl dimethyl(tert-butyl)silyl group and N-isopropylphenyl performed better than others. The reaction catalyzed by NHCs 4c4d with a free hydroxyl group gave the dihydropyranones with reversed diastereoselectivity but decreased enantioselectivity. The reaction went well in THF, toluene, dichloromethane or ether, while the one in toluene showed best results. Better yield was reached when the reaction was carried out at 0 or -20 ℃. Under optimized reaction conditions, a variety of aryl(alkyl)ketenes were investigated for the reaction. It was found that both electron-donating and electron-withdrawing groups in the aryl(alkyl)ketene are tolerable for the reaction. The one with electron-withdrawing substituent gave the product in better yield and diastereoselectivity, while the one with electron-donating substituent resulted in better enantioselectivity. The alkyl chain of the ketenes could be ethyl, n-propyl and n-butyl. All the α-cyanochalcones with para-, meta- or ortho-substitutent went well for the reaction. The absolute configuration of resulted dihydropyranone 3e was established by the X-ray analysis of its crystal. The reaction is proposed to initialize with the addition of NHC to ketenes to give the enolate I. The adduct is formed from enolate I and α-cyanochalcone via stepwise Michael addition and cyclization or simultaneous Diels-Alder reaction. The elimination of NHC from adduct gives final dihydropyranone 3.

Key words: N-heterocyclic carbenes, [4+2] cycloaddition, asymmetric catalysis, dihydropyranones