NHC-Catalyzed Desymmetrizative Amidation for C-O Axially Chiral Imides
Lefeng Lin1, Xin Guan1, Jiuli Xia1
1Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, Department of Chemistry, Northeast Normal University, Changchun 130024, China.
Organic Letters
|March 30, 2026
Summary
This study presents a new N-heterocyclic carbene (NHC)-catalyzed method for synthesizing axially chiral diaryl ethers, specifically benzoimides. This enantioselective approach overcomes challenges associated with low racemization barriers, enabling efficient production of valuable chiral compounds.
Area of Science:
- Organic Chemistry
- Asymmetric Synthesis
- Catalysis
Background:
- Axially chiral diaryl ethers are crucial structural units in various chemical applications.
- The catalytic atroposelective synthesis of these compounds is difficult due to the low energy barrier for racemization around the C-O bond axis.
Purpose of the Study:
- To develop a novel N-heterocyclic carbene (NHC)-catalyzed desymmetrizative amidation strategy.
- To achieve direct enantioselective synthesis of C-O axially chiral benzoimides.
Main Methods:
- Utilized N-heterocyclic carbene (NHC) catalysis.
- Employed readily available aryl amides and axially prochiral diaryl ether dialdehydes.
- Conducted the reaction under mild conditions.
Main Results:
- Successfully synthesized a diverse range of C-O axially chiral benzoimide atropisomers.
- Achieved good to excellent yields (up to 96%) and high enantioselectivities (up to 97:3 er).
- Demonstrated synthetic utility through gram-scale synthesis and downstream transformations without enantiopurity loss.
Conclusions:
- The developed NHC-catalyzed strategy provides an efficient route to enantiomerically enriched C-O axially chiral benzoimides.
- Mechanistic insights suggest the irreversible formation of the Breslow intermediate is key to controlling rate and enantioselectivity.
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