Photocatalytic, Regioselective Enone Deconjugation: An Enabling Platform for Terpene Modification

Alkene relocation to create structural diversity from abundant chemotypes is prevalent in biology but conspicuously underdeveloped in synthetic chemistry. Interconverting constitutional isomers that are partitioned by small energy differences requires intractable thermo- and regiochemical challenges to be overcome, and this continues to limit ground-state positional isomerization. In contrast, light-based activation allows excited-state reactivity to be leveraged to tackle intractable selectivity issues and mimic biochemical isomerization. Emulating steroid Δ⁵-isomerase, a mild photocatalytic deconjugation of cyclohexenone motifs is reported in which a traceless C(sp³)-Br handle is leveraged to bias regioselective generation of a key photodienol. Irradiation with green light (520 nm) in the presence of an organophotoredox catalyst (eosin Y), a base (NaOAc), and a sacrificial reductant (HEH₂) enables the endo-selective debrominative deconjugation of a diverse range of brominated cyclic enones: this expedites access to β-isophorone (an industrial precursor for vitamin and carotenoid synthesis) as well as 3-oxo-Δ⁵-steroids that are common in hormones and oncology drugs (e.g., Zytiga).