Copper-Catalyzed Synthesis of Thiadiazine-1-oxides in Reusable Aqueous Medium Under External [Ag]/Ligand/Base-Free Conditions.

We report herein a copper-catalyzed multicomponent reaction of simple NH-sulfoximine with readily available aldehyde and TMSN3 in hot water and aerobic conditions. The reaction tolerated a broad range of functional groups under external [Ag]/ligand/base-free conditions, and can form three C-N bonds in a one-pot transformation, thus represent an extremely cost-effective protocol to biologically active sulfoximine derivatives. This aqueous catalytic system could be circularly utilized in consecutive runs of gram-scale preparations of thiadiazine-1-oxides without extra addition of copper catalyst and PTA. Mechanistically, an "ortho-binding" effect in ortho-bromo NH-sulfoximine was proposed to control the chemoselectivity, thus, the other free halides such as bromo- or iodo-atoms in aldehydes 2 were compatible in the reaction.

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