Acid-Catalyzed Redox Isomerizations of 6,8-dioxabicyclo[3.2.1]octan-4-ols Provide Mechanistic Insights for Levoglucosenone Formation.

Levoglucosenone is an important platform chemical and the principal product of acid-catalyzed cellulose pyrolysis, formed through several intermediates including levoglucosan. An acid-catalyzed redox isomerization of substituted 6,8-dioxabicyclo[3.2.1]octan-4-ols, which could be considered levoglucosan analogues, has been developed using HBr giving (S)-6-hydroxymethyl-dihydro-2H-pyran-3(4H)-ones. Higher yields were obtained when 3,3-disubstitution was present on the ring-system, and reactions were faster in acetonitrile. Inclusion of ethylene glycol in the reaction mixture led to the in-situ formation of a ketal adduct, which improved the yield for the parent system. A secondary kinetic isotope effect kH/kD of 1.23 for the 3,3-dibenzylated substrate suggested that the mechanism involved elimination rather than hydride transfer, and that ring-opening is the rate-limiting step for the reaction. The facile nature of this transformation further supports a redox-isomerization leading to a glucopyran-2-ulose intermediate in the mechanism leading to levoglucosenone from levoglucosan and cellulose, and may have implications for other acid catalyzed reactions of carbohydrates.