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

Great efforts have been directed toward alkene p bond amination. In contrast, analogous functionalization of the adjacent C(sp(3))-C(sp(2)) s bonds is much rarer. Here we report how ozonolysis and copper catalysis under mild reaction conditions enable alkene C(sp(3))-C(sp(2)) s bond-rupturing cross-coupling reactions for the construction of new C(sp(3))-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, a-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.

Automated summary

In this study, the authors report a cross-coupling reaction that enables the rupture of alkene C(sp(3))-C(sp(2)) bonds using ozonolysis and copper catalysis. This method was used for the construction of new C(sp(3))-N bonds in hormones, pharmaceutical reagents, peptides, and nucleosides. Additionally, the authors demonstrate the synthesis of artificial terpenoid alkaloids and complex chiral amines using abundantly available terpenes and terpenoids.