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
. 2008 Jan 28;64(5):883-893.
doi: 10.1016/j.tet.2007.09.089.

Aza- and Carbo-[3 + 3] Annulations of Exo-Cyclic Vinylogous Amides and Urethanes. Synthesis of Tetrahydroindolizidines and An Unexpected Formation of Hexahydroquinolines

Sunil K Ghosh  1 , Grant S Buchanan, Quincy A Long, Yonggang Wei, Ziyad F Al-Rashid, Heather M Sklenicka, Richard P Hsung
Affiliations

Aza- and Carbo-[3 + 3] Annulations of Exo-Cyclic Vinylogous Amides and Urethanes. Synthesis of Tetrahydroindolizidines and An Unexpected Formation of Hexahydroquinolines

Sunil K Ghosh et al. Tetrahedron. .

Abstract

[3 + 3] Annulations of exo-cyclic vinylogous amides and urethanes with vinyl iminium salts are described here. We observed an intriguing dichotomy in their reaction pathways. For pyrrolidine- and azepane-based vinylogous amides or urethanes, aza-[3 + 3] annulation would dominate to give tetrahydroindolizidines, whereas, unexpectedly, for piperidine-based vinylogous amides or urethanes, carbo-[3 + 3] annulation was the pathway, leading to hexahydroquinolines. The origin for such a contrast is likely associated with a switch in the initial reaction pathway between C-1,2-addition and C-1,4-addition.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Alkaloids Synthesized via Intramolecular Aza-[3 + 3].
Figure 2
Figure 2
Aza-[3 + 3] versus Carbo-[3 + 3] Annluation.
Figure 3
Figure 3
A Possible Synthesis of Tetrahydroindoles.
Figure 4
Figure 4
Energetic Differences in the Annulation Products.
Scheme 1
Scheme 1
An Aza-[3 + 3] Annulation.
Scheme 2
Scheme 2
An Intramolecular Aza-[3 + 3] Annulation.
Scheme 3
Scheme 3
An Aza-[3 + 3] Pathway to Azaphenalenes and Quinolizidines.
Scheme 4
Scheme 4
Syntheses of Exo-Cyclic Vinylogous Amide and Urethane.
Scheme 5
Scheme 5
Unexpected Formation of Hexahydroquinolines.
Scheme 6
Scheme 6
A Proposed Pathway for the Hexahydroquinoline Formation.
Scheme 7
Scheme 7
DDQ Aromatization in the Quinoline Synthesis.
Scheme 8
Scheme 8
C-1,2 Addition versus C-1,4-Addition.
See this image and copyright information in PMC

References

    1. For reviews, see: Harrity JPA, Provoost O. Org Biomol Chem. 2005;3:1349.Hsung RP, Kurdyumov AV, Sydorenko N. Eur J Org Chem. 2005:23.Coverdale HA, Hsung RP. ChemTracts. 2003;16:238.

    1. For a review on vinylogous amide chemistry, see: Kucklander U. Enaminones as Synthons. In: Rappoport Z, editor. The Chemistry of Functional Groups: The Chemistry of Enamines Part I. John Wiley & Sons; New York: 1994. p. 523.

    1. For a theoretical account, see: Wang Y, De-Cai Fang D-C, Liu R-Z. Tetrahedron. 2005;61:5663.

    1. For recent studies in this area, see: Trost BM, Dong G. Org Lett. 2007;9:2357.Schmidt A, Gütlein JP, Mkrrchyan S, Görls H, Langer P. Synlett. 2007:1305.Pattenden LC, Wybrow RAJ, Smith SA, Harrity JPA. Org Lett. 2006;8:3089.Shintani R, Hayashi T. J Am Chem Soc. 2006;128:6330.Halliday JI, Chebib M, Turner P, McLeod MD. Organic Lett. 2006;8:3399.Katsuyama I, Funabiki K, Matsui M, Muramatsu H, Shibata K. Heterocycles. 2006;68:2087.Bose DS, Kumar RK. Heterocycles. 2006;68:549.Goodenough KM, Raubo P, Harrity JPA. Org Lett. 2005;7:2993.Goodenough KM, Moran WJ, Raubo P, Harrity JPA. J Org Chem. 2005;70:207.Agami C, Dechoux L, Hebbe S, Ménard C. Tetrahedron. 2004;60:5433.Ji SJ, Jiang ZQ, Lu J, Loh TP. Synlett. 2004:831.Hedley SJ, Moran WJ, Price DA, Harrity JPA. J Org Chem. 2003;68:4286.

    1. For our work on intermolecular aza-[3 + 3] annulation, see: Sydorenko N, Hsung RP, Darwish OS, Hahn JM, Liu J. J Org Chem. 2004;69:6732.McLaughlin MJ, Hsung RP, Cole KC, Hahn JM, Wang J. Org Lett. 2002;4:2017.Hsung RP, Wei LL, Sklenicka HM, Douglas CJ, McLaughlin MJ, Mulder JA, Yao LJ. Org Lett. 1999;1:509.

LinkOut - more resources