Titanium-Catalyzed Diastereoselective Keto- and Iminonitrile Cyclizations
Christoph Kern1,2, Ritu Singh1, Michael A Unkrig-Bau2
1Department of Chemistry for Life Sciences, Uppsala University, Uppsala, Sweden.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|June 7, 2026
Summary
Synthesizing complex five-membered carbocycles is challenging. This study introduces a titanium-catalyzed method for stereoselective cyclization, yielding valuable oxygenated and aminated cyclopentanones efficiently.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Catalysis
Background:
- Five-membered carbocycles with multiple stereocenters are prevalent in natural products.
- Stereoselective synthesis of these carbocycles remains a significant challenge in organic chemistry.
Purpose of the Study:
- To develop a novel titanium(III)-catalyzed method for the diastereoselective synthesis of substituted five-membered carbocycles.
- To efficiently produce oxygenated and aminated cyclopentanones with high stereocontrol.
Main Methods:
- Titanium(III)-catalyzed cyclization reaction of keto- and iminonitriles.
- Derivatization of cyclized products to access complex cyclopentyl structures.
- Density Functional Theory (DFT) calculations to elucidate the reaction mechanism.
Main Results:
- Achieved good yields and high diastereoselectivity in the formation of oxygenated and aminated cyclopentanones.
- Demonstrated the synthesis of cyclopentyls with three consecutive stereocenters.
- Established a transition state model supported by DFT calculations, consistent with previous findings.
Conclusions:
- The reported titanium(III)-catalyzed cyclization offers an effective route for stereoselective synthesis of complex carbocyclic frameworks.
- The method provides access to valuable intermediates for natural product synthesis.
- Mechanistic insights were gained through computational studies, aiding future catalyst and reaction design.
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