title: Aniline-Promoted Cyclization-Replacement Cascade Reactions of 2-Hydroxycinnamaldehydes with Various Carbonic Nucleophiles through In Situ Formed N,O-Acetals.
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.
authors.affiliation: Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM, 87131-0001, USA.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM, 87131-0001, USA.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM, 87131-0001, USA.|School of Pharmacy, East University of Science and Technology, 130 Mei-Long Road, Shanghai, 200237, P. R. China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM, 87131-0001, USA.
authors.forename: Yueteng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, East University of Science and Technology, 130 Mei-Long Road, Shanghai, 200237, P. R. China. hli77@ecust.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM, 87131-0001, USA. wwang@unm.edu.|School of Pharmacy, East University of Science and Technology, 130 Mei-Long Road, Shanghai, 200237, P. R. China. wwang@unm.edu.
authors.forename: Wei
authors.identifier: http://orcid.org/0000-0001-6043-0860
authors.initials: W
authors.lastname: Wang
mesh_terms: D000080:Acetals / Q000737:chemistry*; D000171:Acrolein / Q000031:analogs & derivatives* / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000814:Aniline Compounds / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D004987:Ethers / Q000737:chemistry; D007211:Indoles / Q000737:chemistry
chemical_list: D000080:Acetals; D000588:Amines; D000814:Aniline Compounds; D004987:Ethers; D007211:Indoles; D002244:Carbon; D000171:Acrolein; C012843:cinnamaldehyde
keywords: N,O-acetals; aminocatalysis; cascade reactions; chromenes; iminium ions