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
. 2014 Jul 8;70(27-28):4147-4155.
doi: 10.1016/j.tet.2014.02.089.

Facile Access to Cyclooctanoid Ring Systems via Microwave-Assisted Tandem 6-exo dig Cyclization-Rearrangement Sequence

Aaron W Feldman  1 , Sami I Ovaska  1 , Timo V Ovaska  1
Affiliations

Facile Access to Cyclooctanoid Ring Systems via Microwave-Assisted Tandem 6-exo dig Cyclization-Rearrangement Sequence

Aaron W Feldman et al. Tetrahedron. .

Abstract

Appropriately substituted 5-alkyn-1-ol systems bearing a nitrile moiety at the triple bond serve as versatile precursors to a variety of cyclooctenone derivatives via a "one-pot" base-catalyzed oxyanionic 6-exo dig cyclization/Claisen rearrangement sequence under microwave irradiation. It was found that the initially formed cyclic intermediate consists of a mixture of endo and exocyclic isomers, which appear to be in equilibrium under the reaction conditions. However, the only observed products from these reactions are α-cyano substituted cyclooctenones, derived from the exocyclic dihydrofuran intermediates.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Representative examples of biologically active cyclooctanoid natural products.
Fig. 2
Fig. 2
Temperature dependent formation of reaction products upon heating 10 in the presence of catalytic base (LHDMS).
Fig. 3
Fig. 3
Time dependence of product formation on heating 10 at 210 °C in the presence of catalytic base (LHDMS).
Figure 4
Figure 4
Chemical shifts of the characteristic vinyl protons present in 12a-c, and 11.
Scheme 1
Scheme 1
General strategy to cycloheptane-containing polycycles via sequential cyclization/Claisen rearrangement reaction.
Scheme 2
Scheme 2
Failed 6-exo dig cyclization/Claisen rearrangement reaction
Scheme 3
Scheme 3
6-exo cyclization/Claisen rearrangement of acetylenic ester 6.
Scheme 4
Scheme 4
Possible mechanism for the base-catalyzed exo/endo isomerization.
Scheme 5
Scheme 5
6-exo cyclization/Claisen rearrangement of a cyano derivative
Scheme 6
Scheme 6
Preparation of acetal-containing 5-alkyn-1-ol systems.
Scheme 7
Scheme 7
6-exo dig cyclization of 10 at room temperature.
See this image and copyright information in PMC

References

    1. For a review, see Mehta G, Singh V. Chem Rev. 1999;99:881.

    1. Petasis NA, Patane MA. Tetrahedron. 1992;48:5757.

    1. [5.1.0]: Paquette LA, Ham WH. J Am Chem Soc. 1987;109:3025.[4.2.0]: Birch AM, Pattenden G. J Chem Soc Chem Comm. 1980:1195.[3.3.0]: Mehta G, Murthy AN. J Org Chem. 1987;52:2875.[4.2.1]: Feldman KS, Ming MJ, Rotella DP. J Am Chem Soc. 1990;112:8490.

    1. For a review, see Ojima I, Tzamarioudaki M, Li Z, Donovan RJ. Chem Rev. 1996;96:635.

    1. Marvell EN, Titterington D. Tetrahedron Lett. 1980:2123.

LinkOut - more resources