Iodoarene-Catalyzed Oxyamination of Unactivated Alkenes to Synthesize 5-Imino-2-Tetrahydrofuranyl Methanamine Derivatives

Reported here is the room-temperature metal-free iodoarene-catalyzed oxyamination of unactivated alkenes. In this process, the alkenes are difunctionalized by the oxygen atom of the amide group and the nitrogen in an exogenous HNTs2 molecule. This mild and open-air reaction provided an efficient synthesis to N-bistosyl-substituted 5-imino-2-tetrahydrofuranyl methanamine derivatives, which are important motifs in drug development and biological studies. Mechanistic study based on experiments and density functional theory calculations showed that this transformation proceeds via activation of the substrate alkene by an in situ generated cationic iodonium(III) intermediate, which is subsequently attacked by an oxygen atom (instead of nitrogen) of amides to form a five-membered ring intermediate. Finally, this intermediate undergoes an S(N)2 reaction by NTs2 as the nucleophile to give the oxygen and nitrogen difunctionalized 5-imino-2-tetrahydrofuranyl methanamine product. An asymmetric variant of the present alkene oxyamination using chiral iodoarenes as catalysts also gave promising results for some of the substrates.

Automated summary

This study describes a room-temperature metal-free iodoarene-catalyzed oxyamination of unactivated alkenes, resulting in the difunctionalization of alkenes by oxygen and nitrogen, leading to the synthesis of important 5-imino-2-tetrahydrofuranyl methanamine derivatives for drug development and biological studies. The mechanism involves activation of substrate alkene by a cationic iodonium(III) intermediate, followed by attack of oxygen atom from amides to form a five-membered ring intermediate, which then undergoes an S(N)2 reaction by NTs2 to give the final product. Promising results were also obtained for some substrates using chiral iodoarenes as catalysts in an asymmetric variant of this alkene oxyamination.