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Formal [4+3] epoxide cascade reaction via a complementary ambiphilic pairing strategy
Alan Rolfe1, Thiwanka B Samarakoon, Paul R Hanson
1Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045, USA.
Organic Letters
|February 25, 2010
Summary
A new [4+3] epoxide cascade protocol efficiently synthesizes benzothiaoxazepine and oxathiazepine dioxides. This method combines epoxide ring-opening with S(N)Ar or oxa-Michael cyclization pathways.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Medicinal Chemistry
Background:
- Cascade reactions offer efficient synthetic routes to complex molecules.
- Sulfonamides are versatile functional groups in organic synthesis.
- Epoxides are valuable synthons for constructing heterocyclic compounds.
Purpose of the Study:
- To develop a novel [4+3] epoxide cascade protocol.
- To synthesize benzothiaoxazepine-1,1'-dioxides and oxathiazepine-1,1'-dioxides.
- To explore the scope and limitations of the developed protocol.
Main Methods:
- Utilizing ambiphilic sulfonamides and various epoxides.
- Employing a formal [4+3] cycloaddition strategy.
- Combining epoxide ring-opening with S(N)Ar or oxa-Michael cyclization.
Main Results:
- Successful synthesis of benzothiaoxazepine-1,1'-dioxides and oxathiazepine-1,1'-dioxides.
- Demonstrated versatility with a range of epoxide substrates.
- Established a new cascade protocol for heterocyclic synthesis.
Conclusions:
- The developed [4+3] epoxide cascade protocol is effective for generating target heterocycles.
- This method provides a valuable addition to the synthetic chemist's toolkit.
- The protocol offers a streamlined approach to complex sulfur- and nitrogen-containing heterocycles.
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