Reactivity Umpolung of Tertiary Amide Enabled by Catalytic Reductive Stannylation

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.

Automated summary

Reactivity umpolung, an important concept in organic chemistry, has mainly focused on aldehydes, with little knowledge about the umpolung of amide carbonyl group. In this report, we present a method to achieve the umpolung reactivity of tertiary amides through efficient reductive stannylation catalyzed by Ir/silane and facile Sn-Li exchange. By utilizing this umpolung reactivity, the drug Fluoxetine was successfully derivatized to 12 different analogues via reactions with various electrophiles, and four biologically active molecules were succinctly prepared. This newly discovered umpolung reactivity of tertiary amides is expected to have applications in synthesizing complex amines from amides.