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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Termination of Mn(III)-based oxidative cyclizations by trapping with azide
Barry B Snider1, Jeremy R Duvall
1Department of Chemistry, MS 015, Brandeis University, Waltham, MA 02454-9110, USA. snider@brandeis.edu
Organic Letters
|April 9, 2004
Summary
This study demonstrates a novel method for synthesizing cyclic and bicyclic azides from beta-keto and malonate esters using manganese(III)-based oxidative cyclizations. Subsequent reduction of these azides yields valuable bi- and tricyclic lactams.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Free Radical Chemistry
Background:
- Manganese(III)-based oxidative cyclizations are established methods for C-C bond formation.
- Trapping of radical intermediates with nucleophiles is a key strategy in organic synthesis.
- Lactams are important structural motifs in pharmaceuticals and natural products.
Purpose of the Study:
- To develop a novel synthetic route to cyclic and bicyclic azides.
- To explore the utility of manganese(III)-based oxidative free-radical cyclizations for azide synthesis.
- To demonstrate the subsequent conversion of azides to lactams.
Main Methods:
- Oxidative free-radical cyclization of beta-keto esters and malonate esters using Mn(III).
- Trapping of intermediate radicals with sodium azide and Mn(III).
- Reduction of the resulting azides to form lactams.
Main Results:
- Cyclic and bicyclic azides were synthesized in 30-80% yields.
- The method is applicable to both beta-keto esters and malonate esters.
- Reduction of the azides successfully afforded bi- and tricyclic lactams.
Conclusions:
- This study presents an efficient strategy for accessing complex cyclic and bicyclic azide scaffolds.
- The developed methodology provides a versatile route to valuable bi- and tricyclic lactam structures.
- The Mn(III)-mediated radical cyclization/trapping sequence offers a powerful tool for synthetic chemists.
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