Tandem singlet oxygenation: Regioselective reaction of two O molecules by a nonconjugated diprenyl phenol.

Tandem reactions of singlet oxygen (O) with nonconjugated natural products, such as plastoquinones, have attracted attention. However, mechanistic clarity is needed for the O uptake sequence and regioselectivity. Our strategy was to study a tandem O reaction in a diprenylated phenol (geranyl phenol) bearing an inner and an outer prenyl group in the chain. Singlet oxygen first added to the inner prenyl group by H-bonding to the phenol OH, forming a gem-disubstituted and a tri-substituted dienyl dihydrobenzofuran. HO was also released as a by-product. A second equivalent of O added by an "ene" reaction, but now to the outer rather than the inner site of the nonconjugated diene to reach four hydroperoxy-dihydrobenzofurans. There was no evidence for O "ene" reactions on the inner prenyl sites, but product decomposition included the formation of oxygen-centered radicals and even methane by a β-scission process. The results are an essential step in resolving mechanistic puzzles of reactive oxygen uptake in natural prenylated systems, which are important topics not only in physical-organic and synthetic chemistry but also in plant oxidation chemistry.