Aniline‐Promoted Cyclization–Replacement Cascade Reactions of 2‐Hydroxycinnamaldehydes with Various Carbonic Nucleophiles through In Situ Formed N,O‐Acetals |
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| Authors: | Chenguang Yu He Huang Xiangmin Li Prof?Dr Yueteng Zhang Hao Li Prof?Dr Wei Wang |
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| Affiliation: | 1. Department of Chemistry & Chemical Biology, University of New Mexico, Albuquerque, NM, USA;2. School of Pharmacy, East University of Science and Technology, Shanghai, P. R. China;3. (+1)?505?277?2609
0000-0001-6043-0860
Department of Chemistry & Chemical Biology, University of New Mexico, Albuquerque, NM, USA |
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| Abstract: | In this study, we report the harnessing of new reactivity of N,O‐acetals in an aminocatalytic fashion for organic synthesis. Unlike widely used strategies requiring the use of acids and/or elevated temperatures, direct replacement of the amine component of the N,O‐acetals by carbon‐centered nucleophiles for C?C bond formation is realized under mild reaction conditions. Furthermore, without necessary preformation of the N,O‐acetals, an amine‐catalyzed in situ formation of N,O‐acetals is developed. Coupling both reactions into a one‐pot operation enables the achievement of a catalytic process. We demonstrate the employment of simple anilines as promoters for the cyclization–substitution cascade reactions of trans‐2‐hydroxycinnamaldehydes with various carbonic nucleophiles including indoles, pyrroles, naphthols, phenols, and silyl enol ethers. The process offers an alternative approach to structurally diverse, “privileged” 2‐substituted 2H‐chromenes. The synthetic power of the new process is furthermore shown by its application in a 2‐step synthesis of the natural product candenatenin E and for the facile installation of 2‐substituted 2H‐chromene moieties into biologically active indoles. |
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| Keywords: | aminocatalysis cascade reactions chromenes iminium ions N O-acetals |
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