title: Direct, Enantioselective Synthesis of Pyrroloindolines and Indolines From Simple Indole Derivatives.
abstract: The (R)-BINOL•SnCl4-catalyzed formal (3 + 2) cycloaddition between 3-substituted indoles and benzyl 2-trifluoroacetamidoacrylate is a direct, enantioselective method to prepare pyrroloindolines from simple starting materials. However, under the originally disclosed conditions, the pyrroloindolines are formed as mixtures of diastereomers, typically in the range of 3:1 to 5:1 favoring theexo-product. The poor diastereoselectivity detracts from the synthetic utility of the reaction. We report here that use of methyl 2-trifluoroacetamidoacrylate in conjunction with (R)-3,3'-dichloro-BINOL•SnCl4provides the corresponding pyrroloindolines with improved diastereoselectivity (typically ≥10:1). Guided by mechanistic studies, a one-flask synthesis of enantioenriched indolines by in situ reduction of a persistent iminium ion is also described.
authors.affiliation: The Warren and Katharine Schlinger Laboratory of Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 (USA).
authors.forename: Jane
authors.initials: J
authors.lastname: Ni
authors.forename: Haoxuan
authors.initials: H
authors.lastname: Wang
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Reisman
keywords: (3 + 2) cycloaddition; enantioselective catalysis; pyrroloindoline
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