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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Enantioselective and Diastereoselective Synthesis of Azaspiro[n.2]alkanes by Rhodium-Catalyzed Cyclopropanations
Joshua K Sailer1, Duc Ly1, Andrew Wang1
1Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States.
Abstract:
Spirocyclopropanes have become a prevalent structural motif in drug discovery campaigns. However, methods to generate these spirocyclopropanes stereoselectively are scarce, highlighting the need for efficient synthetic methods. In this report, we describe the synthesis of various azaspiro-[n.2]-alkanes by means of a dirhodium tetracarboxylate catalyzed cyclopropanation of exocyclic olefins using donor/acceptor carbenes. The optimum chiral dirhodium tetracarboxylate catalyst, Rh2(p-PhTPCP)4, results in highly enantioselective cyclopropanation of symmetrical azacyclomethylidenes and highly enantioselective and diastereoselective cyclopropanation of nonsymmetrical azacyclomethylidenes and can achieve up to 83,000 turnovers. Computational studies reveal that the stereoselectivity is controlled by the way the substrate can fit into the chiral pocket generated by the ligands.
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