Reactivity Umpolung of Tertiary Amide Enabled by Catalytic Reductive Stannylation

Abstract Reactivity umpolung is an important concept in organic chemistry. Established reactivity umpolung mainly focuses on the aldehyde and umpolung of amide carbonyl group is not known. In this report, we describe a process to obtain the umpolung reactivity of tertiary amide. This process hinges on the efficient reductive stannylation catalyzed by Ir/silane and facile Sn−Li exchange. By leveraging this umpolung reactivity, drug Fluoxetine was derivatized to 12 different analogues via reacting with various electrophiles and four biologically active molecules were prepared concisely. This unlocked umpolung reactivity of tertiary amide is expected to find applications to synthesize complex amines from amides.