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Direct, enantioselective synthesis of pyrroloindolines and indolines from simple indole derivatives

Wang, Jane Ni Haoxuan and Reisman, Sarah E. (2013) Direct, enantioselective synthesis of pyrroloindolines and indolines from simple indole derivatives. Tetrahedron, 69 (27-28). pp. 5622-5633. ISSN 0040-4020. PMCID PMC3769991. doi:10.1016/j.tet.2013.04.003. https://resolver.caltech.edu/CaltechAUTHORS:20130802-142338946

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Abstract

The (R)-BINOL·SnCl_4-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 the exo-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·SnCl_4 provides 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.tet.2013.04.003DOIArticle
http://www.sciencedirect.com/science/article/pii/S0040402013005152PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769991/PubMed CentralArticle
ORCID:
AuthorORCID
Reisman, Sarah E.0000-0001-8244-9300
Additional Information:© 2013 Elsevier Ltd. Received 18 January 2013. Received in revised form 28 March 2013. Accepted 1 April 2013. Available online 6 April 2013. We thank Dr. David VanderVelde for assistance with NMR structure determination, as well as Prof. Brian Stoltz, Dr. Scott Virgil, and the Caltech Center for Catalysis and Chemical Synthesis for access to analytical equipment. We also thank Sigma-Aldrich for a kind donation of chemicals. NMR spectra were obtained on a spectrometer funded by the NIH (RR027690). Fellowship support was provided by Natural Sciences and Engineering Research Council (NSERC) of Canada (J.N., PGS D scholarship). S.E.R. is a fellow of the Alfred P. Sloan Foundation and a Camille Dreyfus Teacher-Scholar. Financial support from the California Institute of Technology, the NIH (NIGMS RGM097582A), and the donors of the ACS Petroleum Research Fund is gratefully acknowledged.
Funders:
Funding AgencyGrant Number
Sigma-AldrichUNSPECIFIED
NIHRR027690
Natural Sciences and Engineering Research Council (NSERC) of CanadaUNSPECIFIED
CaltechUNSPECIFIED
NIHRGM097582A
American Chemical Society Petroleum Research FundUNSPECIFIED
Subject Keywords: Pyrroloindoline; (3+2) cycloaddition; Enantioselective catalysis
Issue or Number:27-28
PubMed Central ID:PMC3769991
DOI:10.1016/j.tet.2013.04.003
Record Number:CaltechAUTHORS:20130802-142338946
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20130802-142338946
Official Citation:Jane Ni, Haoxuan Wang, Sarah E. Reisman, Direct, enantioselective synthesis of pyrroloindolines and indolines from simple indole derivatives, Tetrahedron, Volume 69, Issues 27–28, 8 July 2013, Pages 5622-5633, ISSN 0040-4020, http://dx.doi.org/10.1016/j.tet.2013.04.003. (http://www.sciencedirect.com/science/article/pii/S0040402013005152)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39742
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:02 Aug 2013 21:50
Last Modified:09 Nov 2021 23:46

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