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Published on: February 16, 2018
Reductive hydroxyalkylation/alkylation of amines with lactones/esters.
Yu-Huang Wang1, Jian-Liang Ye, Ai-E Wang
1Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P.R. China.
Organic & Biomolecular Chemistry
|July 4, 2012
Summary
A new one-pot synthesis directly converts lactones and esters into alkylated or hydroxyalkylated amines using diisobutylaluminium hydride (DIBAL-H). This reductive amidation method offers a versatile route to diverse amine products.
Area of Science:
- Organic Chemistry
- Synthetic Methodology
- Catalysis
Background:
- Reductive amination is a fundamental transformation in organic synthesis.
- Existing methods often require multiple steps or harsh conditions.
- Developing efficient and direct routes to functionalized amines remains a key challenge.
Purpose of the Study:
- To develop a novel one-pot method for the direct intermolecular reductive hydroxyalkylation or alkylation of amines.
- To utilize readily available lactones and esters as hydroxyalkylating or alkylating reagents.
- To establish a versatile and efficient synthetic strategy for amine synthesis.
Main Methods:
- A one-pot procedure involving in situ amidation of lactones/esters with a diisobutylaluminium hydride (DIBAL-H)-amine complex.
- Subsequent reduction of the intermediate amides using an excess of DIBAL-H.
- Application of the method to both primary and secondary amines using appropriate DIBAL-H complexes.
Main Results:
- Successful direct intermolecular reductive hydroxyalkylation/alkylation of amines.
- The method is effective with both lactones and esters as starting materials.
- Formation of amines, contrasting with aldehyde formation from typical Weinreb amide reductions.
Conclusions:
- A novel and efficient one-pot method for synthesizing functionalized amines has been established.
- The developed reductive amidation strategy offers a versatile alternative to existing methods.
- The reaction proceeds through in situ formation and reduction of amides, applicable beyond Weinreb amides.
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