Biomimetic Cationic Cyclopropanation Enables an Efficient Chemoenzymatic Synthesis of 6,8-Cycloeudesmanes

Cationic cyclopropanation involves the gamma-elimina-tion at carbocations to form a new sigma-C-C bond through proton loss. While exceedingly rare in bulk solution, it is recognized as one of the main biosynthetic cyclopropanation pathways. Despite the rich history of bioinspired synthetic chemistry, cationic cyclopropanation has not been appropriated for the synthetic toolbox, likely due to the preference of carbocations to undergo competing E1 beta-elimination pathways. Here, we present an in-depth synthetic and computational study of cationic cyclopropanation, focusing on the 6,8-cycloeudesmanes as a platform for this investigation. We were able to apply biomimetic cationic cyclopropanation to the synthesis of several 6,8-cycloeudesmanes and non-natural analogues-in doing so, we showcase the power of this transformation in the preparation of complex cyclopropanes.

Automated summary

Cationic cyclopropanation is a rare but important biosynthetic pathway involving the formation of a new sigma-C-C bond through the elimination of carbocations. Despite the historical influence of bioinspired synthetic chemistry, cationic cyclopropanation has not been widely used due to the preference of carbocations for competing elimination pathways. In this study, we conducted a synthetic and computational investigation of cationic cyclopropanation using 6,8-cycloeudesmanes as a platform, and successfully applied it to the synthesis of complex cyclopropanes.