All at once arrangement of both oxygen atoms of dioxygen into aliphatic C(sp3)-C(sp3) bonds for hydroxyketone difunctionalization

Abstract

Both β- and γ- hydroxyketone structures are important units in biologically active molecules, synthetic drugs and fine chemicals. Although there are some routes available for their manufacture from pre-functionalized groups on one or two matrix molecule(s), the approaches to simply and simultaneously deposit two oxygen atoms from dioxygen into two specific C(sp3) positions of pure saturated hydrocarbons have rarely succeeded because they are involved in the targeted activation of three inert C-H σ bonds all at once. Here, we show that a TiO2-CH3CN photocatalytic suspension system enables the insertion of dioxygen into one C(sp3)-C(sp3) bond of strained cycloparaffin derivatives, by which difunctionalized hydroxyketone products are obtained in a one-pot reaction. With the cleavage event to release strain as the directional driving force, as-designed photocatalytic reaction systems show 21 examples of β-hydroxyketone products with 31%–76% isolated yields for three-membered ring derivatives and 5 examples of γ-hydroxyketone products with 30%–63% isolated yields for four-membered ring substrates. 18O isotopic labeling experiments using 18O2, Ti18O2 and intentionally added H218O, respectively, indicated that both oxygen atoms of hydroxyketone products were exclusively from dioxygen, suggesting a previously unknown H+/TiO2-e− catalyzed arrangement pathway of the hydroperoxide intermediate to convert dioxygen into hydroxyketone units.