Ligand-Controlled Chemodivergent Telomerization and Hydrofunctionalization of Isoprene With Hydrazones Under Ni Catalysis.

Terpenoids represent one of the most structurally diverse and biologically relevant families of natural products, yet the development of controllable biomimetic synthetic strategies using bulk feedstocks remains a critical challenge. Isoprene, an abundant and atom-economical building block, holds great promise for terpenoid synthesis, but its four electronically and sterically similar olefinic carbons generally lead to poor regioselectivity and uncontrollable chemoselectivity in catalytic transformations. In this study, we reported a nickel-catalyzed chemodivergent telomerization and hydrofunctionalization reaction for constructing terpenoids, wherein precise ligand control enables selective reactivity tuning. Leveraging the in situ formation of benzyl group from hydrazone-mediated carbonyl umpolung reaction, telomerization is promoted by triarylphosphine ligand featuring both large steric hindrance and electron-donating characteristics, while hydrofunctionalization benefits from the combination of less bulky, electron-withdrawing triarylphosphine ligand and BEt3. Mechanistic studies and density functional theory calculations validate the chemoselectivity governed by ligand sterics and electronics, as well as the role of BEt3 in enhancing regioselectivity. Moreover, this protocol created a series of value-added terpenoids, all of which are amenable to further structural derivatizations. This mild, operationally simple catalytic manifold enables facile access to unnatural terpenoids and broadens the accessible chemical space of terpene frameworks.