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.
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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. | ||||||||||||||
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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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