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
. 2010 Nov 30;107(48):20655-60.
doi: 10.1073/pnas.1005296107. Epub 2010 Aug 12.

Lewis base catalysis of bromo- and iodolactonization, and cycloetherification

Scott E Denmark  1 , Matthew T Burk
Affiliations

Lewis base catalysis of bromo- and iodolactonization, and cycloetherification

Scott E Denmark et al. Proc Natl Acad Sci U S A. .

Abstract

Lewis base catalyzed bromo- and iodolactonization reactions have been developed and the effects of catalyst structure on rate and cyclization selectivity have been systematically explored. The effects of substrate structure on halolactonization reactions and the interaction of those effects with the effects of catalyst structure have been investigated, leading to synthetically useful improvements in cyclization selectivity. The knowledge acquired was applied to the development of Lewis base catalyzed bromo- and iodocycloetherification reactions. The ability of some of the surveyed catalysts to influence the cyclization selectivity of halolactonization reactions demonstrates their presence in the transition structure of the product-determining cyclization step. This observation implies that chiral derivatives of these catalysts have the potential to provide enantioenriched products regardless of the rates or mechanisms of halonium ion racemization.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
General scheme of halocyclization reactions.
Fig. 2.
Fig. 2.
The racemization of halonium ions by degenerate exchange; nondegeneracy induced by the presence of a chiral Lewis base.
Fig. 3.
Fig. 3.
Scope of Lewis base catalyzed bromolactonization.
Fig. 4.
Fig. 4.
Scope of Lewis base catalyzed bromocycloetherification.
Fig. 5.
Fig. 5.
Scope of Lewis base catalyzed iodolactonization.
Fig. 6.
Fig. 6.
Stability of isomeric iodolactones to iodolactonization conditions.
Fig. 7.
Fig. 7.
Scope of Lewis base catalyzed iodocycloetherification.
Fig. 8.
Fig. 8.
Proposed role of timing of proton transfer on the mechanism of halolactonization.
See this image and copyright information in PMC

References

    1. Ranganathan S, Muraleedharan KM, Vaish NK, Jayaraman N. Halo- and selenolactonization: the two major strategies for cyclofunctionalization. Tetrahedron. 2004;60:5273–5308.
    1. Laya MS, Banerjee AK, Cabrera EV. Iodolactonization: past and present examples. Curr Org Chem. 2009;13:720–730.
    1. Cardillo G, Orena M. Sterocontrolled cyclofunctionalizations of double bonds through heterocyclic intermediates. Tetrahedron. 1990;46:3321–3408.
    1. Dowle MD, Davies DI. Synthesis and synthetic utility of halolactones. Chem Soc Rev. 1979;8:171–197.
    1. French AN, Bissmire S, Wirth T. Iodine electrophiles in stereoselective reactions: recent developments and synthetic applications. Chem Soc Rev. 2004;33:354–362. - PubMed

Publication types

LinkOut - more resources