Acid-Catalyzed Redox Isomerizations of 6,8-dioxabicyclo3.2.1octan-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.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.