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Catalytic Asymmetric Access to Structurally Diverse N-Alkoxy Amines via a Kinetic Resolution Strategy
Min Cao1,2, Zehua Wang2, Fangao Hou2
1School of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University, Jinan 250117, Shandong, China.
Abstract:
Chiral N-alkoxy amines are increasingly vital substrates in bioscience. However, asymmetric synthetic strategies for these compounds remain scarce. Catalytic kinetic resolution represents an attractive approach to prepare structurally diverse enantiopure N-alkoxy amines, which has remained elusive due to the notably reduced nucleophilicity of the nitrogen atom together with the low bond dissociation energies of labile NO-C and N-O bonds. We here report a general kinetic resolution of N-alkoxy amines through chemo- and enantioselective oxygenation. The mild and green titanium-catalyzed approach features broad substrate scope (55 examples), noteworthy functional group compatibility, high catalyst turnover number (up to 5200), excellent selectivity factor (s > 150), and scalability.
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