Kennedy oxidative cyclization

What is Kennedy oxidative cyclization?

In 1992, Kennedy discovered a highly stereoselective reaction that converts 5-hydroxyl alkene into a trans-tetrahydrofuran derivative with erythro stereochemistry at the two vicinal carbinol centers. This reaction is known as the Kennedy oxidative cyclization and is promoted by rhenium (VII) oxide (Re2O7) through syn-oxidative cyclization.

Kennedy oxidative cyclization - general reaction scheme
Kennedy oxidative cyclization

During this reaction, the hydroxy group of the substrate binds to Re2O7, and the substrate itself transforms into an alkoxyperrhenate intermediate, accompanied by the formation of perrhenic acid (HOReO3). The Re=O double bond couples with the carbon-carbon double bond through [2+2] addition, leading to the release of the tetrahydrofuran derivative through reductive elimination. Interestingly, when the oxidative cyclization is promoted with VO(acac)2, it yields a cis-tetrahydrofuran ring with threo stereochemistry at the two vicinal carbinol centers.

Kennedy oxidative cyclization is highly effective in converting polyenes into polyoxygenated chiral derivatives, especially when combined with the Sharpless asymmetric oxidation. It has been successfully applied to the synthesis of many acetogenins of the first and second subgroups, including solamin, reticulatacin, asimicin, bullatacin, trilobacin, and trilobin.