Acta Chimica Sinica ›› 2012, Vol. 70 ›› Issue (16): 1682-1685.DOI: 10.6023/A12070444 Previous Articles     Next Articles



孙峋皓, 彭景, 张叔阳, 周清清, 董琳, 陈应春   

  1. 四川大学华西药学院 靶向药物与释药系统教育部重点实验室 成都 610041
  • 投稿日期:2012-07-19 发布日期:2012-08-15
  • 通讯作者: 陈应春
  • 基金资助:
    项目受国家自然科学基金(Nos. 21125206, 21021001)资助.

Asymmetric Allylic Alkylation of Cyclic N-Sulfonylimines with Morita-Baylis-Hillman Carbonates of Isatins

Sun Xunhao, Peng Jing, Zhang Shuyang, Zhou Qingqing, Dong Lin, Chen Yingchun   

  1. Key Laboratory of Drug-Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
  • Received:2012-07-19 Published:2012-08-15
  • Supported by:
    Project supported by the National Natural Science Foundation of China (Nos. 21125206, 21021001).

Enantiomerically pure 3,3-disubstituted 2-oxindoles are important building blocks for the synthesis of diverse oxindoles which are the core structure of many natural products and biologically active compounds. A number of asymmetric reactions to access such chiral materials have been reported over the past years, most of which rely on the application of nucleophilic 3-subsituted oxindoles. Although these methods have been proved to be useful, some challenging issues still remain in terms of efficiency, stereoselectivity and substrate scope. On the other hand, recently, we have developed some highly stereoselective allylic alkylation reactions with Morita-Baylis-Hillman (MBH) carbonates of isatins and diverse nucleophiles, to produce 3,3-disubstituted oxindoles under the catalysis of metal-free Lewis basic tertiary amines. In this work, the first asymmetric assembly of MBH carbonates of isatins and cyclic N-sulfonylimines is reported. An array of tertiary amine catalysts derived from β-isocupreidine (β-ICD) and a variety of reaction parameters have been systematically investigated, and the optimized conditions were determined to run the reaction at -20 ℃ using PhCF3 as the solvent, 4 Å MS as the additive, in the presence of 10 mol% of amine catalyst 1h. A number of MBH carbonates 2 derived from diversely substituted isatins and cyclic N-sulfonylimines 3 could be well tolerated under the established catalytic conditions, providing an alternative electrophilic pathway to access multifunctional oxindoles bearing adjacent quaternary and tertiary stereogenic centers (up to 86% ee, dr>95∶5) in high yield (up to 96%). Moreover, the thus obtained chiral 3,3-disubstituted 2-oxindole could be used for the synthesis of complex spirocyclic 2-oxindole-3,4'-piperidine product. In this case, the chemoselective reduction of imine group of allylic alkylation product 4a has been realized by using NaBH4 as the reducing reagent at -20 ℃. A following intramolecular aza-Michael addition reaction gave a 2-oxindole-3,4'-piperidine product 6 in a moderate yield.

Key words: asymmetric organocatalysis, allylic alkylation, Morita-Baylis-Hillman carbonates, cyclic N-sulfonylimines, 2-oxindoles, quaternary chiral centre, 2-oxindole-3,4'-piperidine