Bridging terpenyl aldehydes and terpenes with hydrazine

Abstract

In nature, terpenoids are typically biosynthesized through the catalysis of specific enzymes, while the artificial synthesis of unnatural terpenoids has garnered increasing attention. Herein, we have developed a molecular-bridging strategy that enables the preparation of unnatural terpenoids from natural terpenyl aldehydes and terpenes, expanding the potential applications of natural terpenoids. This reactivity hinges on the strategic use of Ts-hydrazine as a crucial mediator, which enables molecular bridging through pyrazole formation. More importantly, the modular molecular synthesis strategy could significantly expand the structural diversity space of the terpenoid family through precisely tunable building-block assembly. Furthermore, the resulting pyrazole moiety can be subjected to further modification, enhancing the synthetic utility of this strategy.