Asymmetric α-spirocyclopropanation of oxindoles and benzofuranones via dynamic kinetic resolution
Yang Hu1,2, Jie Yuan1,2, Zheyao Li1,2
1Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, People's Republic of China.
Abstract:
Chiral benzo five-membered heterocyclic spirocyclopropanes are an important class of parent core structures with pharmacological activity. A novel organocatalytic one-pot cascade ether oxidation iminium-ion activation strategy for the asymmetric spirocyclopropylation of benzofuran-2-ones and indolin-2-ones from allyl tert-butyl ethers/ pent-2,4-dienyl ethyl ethers with excellent enantioselectivity (ee% up to > 99) and diastereoselectivity(dr.% up to 91:9) has been developed. This process involves the successful dynamic kinetic resolution of racemic 3-bromobenzofuran-2-ones or 3-bromoindolin-2-ones. Its synthetic application will provide a new aminocatalytic cascade tool for the efficient synthesis of complex molecules.
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