From Cycloalkanols to Heterocycles via Nitrogen Insertion
Alexander Sandvoß1, Johannes M Wahl1
1Department Chemie, Johannes Gutenberg-Universität, Duesbergweg 10-14, 55128 Mainz, Germany.
Organic Letters
|July 28, 2023
Summary
Cyclic alcohols can be converted into nitrogen-containing heterocycles using O-mesitylsulfonylhydroxylamine in fluorinated solvents. This method provides access to medicinally relevant compounds and novel indole synthesis pathways.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Medicinal Chemistry
Background:
- Nitrogen insertion into cyclic alcohols is a key transformation for synthesizing heterocyclic compounds.
- Developing efficient and versatile methods for accessing medicinally relevant scaffolds is crucial in drug discovery.
Purpose of the Study:
- To develop a novel transition-metal-free method for nitrogen insertion into cyclic alcohols.
- To explore the synthesis of medicinally relevant heterocycles and indoles using this new methodology.
Main Methods:
- Reaction of cyclic alcohols with O-mesitylsulfonylhydroxylamine in fluorinated alcoholic solvents.
- Utilizing photochemical Norrish-Yang-type cyclization for indole synthesis.
Main Results:
- Successful nitrogen insertion into various cyclic alcohols, yielding 24 examples of medicinally relevant heterocycles like pyrrolidenes, quinolines, and benzazepines.
- Demonstrated an unprecedented access to indoles from ortho-substituted acetophenones via a combined photochemical cyclization approach.
Conclusions:
- The developed method offers a facile and efficient route to diverse nitrogen-containing heterocycles.
- This approach expands synthetic capabilities for accessing valuable pharmaceutical building blocks and novel indole derivatives.
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