Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 May;44(10):1481-1484.
doi: 10.1055/s-0031-1289762. Epub 2012 Apr 22.

Multigram Synthesis of a Chiral Substituted Indoline Via Copper-Catalyzed Alkene Aminooxygenation

Fatima C Sequeira  1 , Michael T Bovino, Anthony J Chipre, Sherry R Chemler
Affiliations

Multigram Synthesis of a Chiral Substituted Indoline Via Copper-Catalyzed Alkene Aminooxygenation

Fatima C Sequeira et al. Synthesis (Stuttg). 2012 May.

Abstract

(S)-5-Fluoro-2-(2,2,6,6-tetramethylpiperidin-1-yloxymethyl)-1-tosylindoline, a 2-methyleneoxy-substituted chiral indoline, was synthesized on multigram scale using an efficient copper-catalyzed enantioselective intramolecular alkene aminooxygenation. The synthesis is accomplished in four steps and the indoline is obtained in 89% ee (>98% after one recrystallization). Other highlights include efficient gram-scale synthesis of the (4R,5S)-di-Ph-box ligand and efficient separation of a monoallylaniline from its bis(allyl)aniline by-product by distillation under reduced pressure.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1
Copper-catalyzed enantioselective indoline synthesis
Scheme 2
Scheme 2
Reduction of the N–O bond gives the alcohol
See this image and copyright information in PMC

References

    1. Anas S, Kagan HB. Tetrahedron: Asymmetry. 2009;20:2193.
    1. Fuller PH, Kim J-W, Chemler SR. J. Am. Chem. Soc. 2008;130:17638. - PMC - PubMed
    2. Liwosz TW, Chemler SR. J. Am. Chem. Soc. 2012;134:2020. - PMC - PubMed
    3. Bovino MT, Chemler SR. Angew. Chem. Int. Ed. 2012;51:3923. - PMC - PubMed
    1. Seaman W, Norton AR, Woods JT, Bank HN. J. Am. Chem. Soc. 1945;67:1571.
    2. Goetz-Luthy N. J. Chem. Educ. 1949;26:271.
    3. Bannister WW, Pennace JR, Smith DW, Chelton CF, Wareing JA, Curby WA. J. Chem. Educ. 1973;50:578.

    1. Original synthesis of ligand 3: Masamune S, Lowenthal RE. Chem. Abstr. ??? 1994 US Patent 5298623 A 19940329, The method used in the present work: Denmark SE, Stiff CM. J. Org. Chem. 2000;65:5875.

    1. a We believe loss of conversion upon scale-up is due to self-quenching of the TEMPO radical (disproportionation), which O2 might prevent. TEMPO reactivity: Vogler T, Studer A. Synthesis. 2008:1979.