Austin, Joel F. and MacMillan, David W. C. (2002) Enantioselective Organocatalytic Indole Alkylations. Design of a New and Highly Effective Chiral Amine for Iminium Catalysis. Journal of the American Chemical Society, 124 (7). pp. 1172-1173. ISSN 0002-7863. doi:10.1021/ja017255c. https://resolver.caltech.edu/CaltechAUTHORS:20170411-110954305
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Abstract
The indole framework has become widely identified as a “privileged” structure with representation in over 3000 natural isolates and 40 medicinal agents of diverse therapeutic action. A new strategy for asymmetric access to this important pharmacaphore has been accomplished that involves the amine catalyzed alkylation of indoles with α,β-unsaturated aldehydes. Central to these studies has been the design of a new chiral amine catalyst that exhibits improved reactivity and selectivity for iminium catalysis. This new (2S,5S)-5-benzyl-2-tert-butyl-imidazolidinone catalyst has enabled the conjugate addition of a variety of indole systems to a diverse range of α,β-unsaturated aldehydes in high yield and with excellent levels of enantiocontrol (70−97% yield, 84−97% ee). A demonstration of the utility of this new organocatalytic alkylation for the rapid construction of biomedically relevant molecules is presented in the enantioselective synthesis of an indolobutyric acid COX-2 inhibitor.
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Additional Information: | © 2002 American Chemical Society. Received October 7, 2001. Publication Date (Web): January 26, 2002. Financial support was provided by kind gifts from Astra-Zeneca, Dupont, GlaxoSmithKline, Johnson and Johnson, Materia, Merck Research Laboratories and Roche Biosciences. We also thank Great Lakes for their generous donation of (S)-phenylalanine. | ||||||||||||||||
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Issue or Number: | 7 | ||||||||||||||||
DOI: | 10.1021/ja017255c | ||||||||||||||||
Record Number: | CaltechAUTHORS:20170411-110954305 | ||||||||||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20170411-110954305 | ||||||||||||||||
Official Citation: | Enantioselective Organocatalytic Indole Alkylations. Design of a New and Highly Effective Chiral Amine for Iminium Catalysis Joel F. Austin and David W. C. MacMillan Journal of the American Chemical Society 2002 124 (7), 1172-1173 DOI: 10.1021/ja017255c | ||||||||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||||
ID Code: | 76510 | ||||||||||||||||
Collection: | CaltechAUTHORS | ||||||||||||||||
Deposited By: | Tony Diaz | ||||||||||||||||
Deposited On: | 11 Apr 2017 19:51 | ||||||||||||||||
Last Modified: | 15 Nov 2021 17:00 |
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