Aminodealkenylation: Ozonolysis and copper catalysis convert C(sp3)-C(sp2) bonds to C(sp3)-N bonds.

Abstract

Great efforts have been directed toward alkene π bond amination. In contrast, analogous functionalization of the adjacent C(sp3)-C(sp2) σ bonds is much rarer. Here we report how ozonolysis and copper catalysis under mild reaction conditions enable alkene C(sp3)-C(sp2) σ bond-rupturing cross-coupling reactions for the construction of new C(sp3)-N bonds. We have used this unconventional transformation for late-stage modification of hormones, pharmaceutical reagents, peptides, and nucleosides. Furthermore, we have coupled abundantly available terpenes and terpenoids with nitrogen nucleophiles to access artificial terpenoid alkaloids and complex chiral amines. In addition, we applied a commodity chemical, α-methylstyrene, as a methylation reagent to prepare methylated nucleosides directly from canonical nucleosides in one synthetic step. Our mechanistic investigation implicates an unusual copper ion pair cooperative process.