Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published February 20, 2002 | Supplemental Material
Journal Article Open

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

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.

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.

Attached Files

Supplemental Material - ja017255c_s1.pdf

Files

ja017255c_s1.pdf
Files (90.4 kB)
Name Size Download all
md5:0796fd880f6623f0d66eed2e3efa07ab
90.4 kB Preview Download

Additional details

Created:
August 19, 2023
Modified:
October 25, 2023