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
. 2011 Jun 3;13(11):2932-5.
doi: 10.1021/ol2009895. Epub 2011 May 10.

Enantioconvergent synthesis of (+)-aphanorphine via asymmetric Pd-catalyzed alkene carboamination

Duy N Mai  1 , Brandon R Rosen, John P Wolfe
Affiliations

Enantioconvergent synthesis of (+)-aphanorphine via asymmetric Pd-catalyzed alkene carboamination

Duy N Mai et al. Org Lett. .

Abstract

A concise asymmetric synthesis of (+)-aphanorphine has been achieved via a new enantioconvergent strategy. A racemic γ-aminoalkene derivative is transformed into a 1:1 mixture of enantiomerically enriched diastereomers using an asymmetric Pd-catalyzed carboamination. This mixture is then converted to an enantiomerically enriched protected aphanorphine derivative by a Friedel-Crafts reaction, which generates a quaternary all-carbon stereocenter. The natural product is obtained in three additional steps.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Benzomorphane Alkaloids
Scheme 1
Scheme 1
Asymmetric Carboamination/Friedel-Crafts Alkylation Strategy
Scheme 2
Scheme 2
Synthesis of Carboamination Substrate
Scheme 3
Scheme 3
Pd-Catalyzed Carboamination of 5 and Conversion to 13.
Scheme 4
Scheme 4
Completion of the Synthesis
See this image and copyright information in PMC

References

    1. Gulavita N, Hori A, Shimizu Y, Laszlo P, Clardy J. Tetrahedron Lett. 1988;29:4381–4384.

    1. For recent syntheses of (−)-aphanorphine, see: Medjahdi M, González-Gómez JC, Foubelo F, Yus M. Eur Org Chem. 2011:2230–2234.Donets PA, Goeman JL, Van der Eycken J, Robeyns K, Van Meervelt L, Van der Eycken EV. Eur J Org Chem. 2009:793–796.Yang X, Cheng B, Li Z, Zhai H. Synlett. 2008:2821–2822.Yang X, Zhai H, Li Z. Org Lett. 2008;10:2457–2460.Grainger RS, Welsh EJ. Angew Chem Int Ed. 2007;46:5377–5380.Li M, Zhou P, Roth HF. Synthesis. 2007:55–60.Bower JF, Szeto P, Gallagher T. Org Biomol Chem. 2007;5:143–150.

    1. For syntheses of (−)-aphanorphine prior to 2007, see: Takano S, Inomata K, Sato T, Takahashi M, Ogasawara K. J Chem Soc, Chem Commun. 1990:290–292.Bower JF, Szeto P, Gallagher T. Chem Commun. 2005:5793–5795.and references cited therein.

    1. For syntheses of (+)-aphanorphine, see reference 2a and: Ma Z, Zhai H. Synlett. 2007:161–163.Ma Z, Hu H, Xiong W, Zhai H. Tetrahedron. 2007;63:7523–7531.Katoh M, Inoue H, Honda T. Heterocycles. 2007;72:497–516.Katoh M, Inoue H, Suzuki A, Honda T. Synlett. 2005:2820–2822.Meyers AI, Schmidt W, Santiago B. Heterocycles. 1995;40:525–529.Takano S, Inomata K, Sato T, Ogasawara K. J Chem Soc, Chem Commun. 1989:1591–1592.

    1. Fadel A, Arzel P. Tetrahedron: Asymmetry. 1995;6:893–900.
    2. Kita Y, Futamura J, Ohba Y, Sawama Y, Ganesh JK, Fujioka H. J Org Chem. 2003;68:5917–5924. - PubMed
    3. Taylor SK, Ivanovic M, Simons LJ, Davis MM. Tetrahedron: Asymmetry. 2003;14:743–747.

Publication types