CaltechAUTHORS
  A Caltech Library Service

Enantioselective Organocatalytic Indole Alkylations. Design of a New and Highly Effective Chiral Amine for Iminium Catalysis

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. https://resolver.caltech.edu/CaltechAUTHORS:20170411-110954305

[img] PDF (Experimental procedures and spectral data for all compounds) - Supplemental Material
See Usage Policy.

88Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20170411-110954305

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja017255cDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja017255cPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ja017255cPublisherSupporting Information
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.
Funders:
Funding AgencyGrant Number
Astra-ZenecaUNSPECIFIED
DupontUNSPECIFIED
GlaxoSmithKlineUNSPECIFIED
Johnson and JohnsonUNSPECIFIED
MateriaUNSPECIFIED
Merck Research LaboratoriesUNSPECIFIED
Roche BiosciencesUNSPECIFIED
Issue or Number:7
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:03 Oct 2019 17:02

Repository Staff Only: item control page