Rate enhancement of lipase-catalyzed reaction using CO2-expanded liquids as solvents for chiral tetralol synthesis

• Published in: Tetrahedron letters Vol. 99; p. 153837
• Main Authors: Suzuki, Yuichi, Taniguchi, Kosuke, Hoang, Hai Nam, Tamura, Mayumi, Matsuda, Tomoko
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 08.06.2022
• Subjects: 1-Tetralol; 2-Tetralol; Bio-based liquid; carbon dioxide; Chiral compound; CO2-expanded liquid; fossil fuels; Lipase; solvents; Chiral compound; 2-Tetralol; Lipase; CO2-expanded liquid; Bio-based liquid; 1-Tetralol
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2022.153837

[Display omitted] •The investigation of the applicability of CO2 as a solvent is important.•The CO2-expanded liquids as solvents for a lipase-catalyzed reaction were examined.•CO2-expanded MeTHF accelerated the reaction rate by up to 40 times that without CO2.•Chiral tetralols, important drug intermediates, were synthesized (ee up to > 99%). The investigation on the applicability of CO2 as a solvent has been increasingly important due to the need to develop efficient reactions replacing ordinary organic solvents derived from fossil fuel with sustainable solvents such as pressurized CO2. In our previous study of solvent engineering of a lipase-catalyzed reaction of bulky substrates, the conversions were higher for the reaction in CO2-expanded liquids, liquids expanded by dissolving pressurized CO2, than that in the liquids without CO2. This study demonstrates the detailed examination of CO2-expanded liquids as solvents for lipase-catalyzed kinetic resolution of racemic 1-tetralol, 2-tetralol, and substituted 1-tetralol analogs since chiral substituted tetralol analogs are important pharmaceutical intermediates. CO2-expanded liquids accelerated the reaction rate by up to 40 times of the reactions without CO2 while maintaining excellent enantioselectivities (E > 200). Preparative scale reactions of racemic 1-tetralol and 2-tetralol successfully gave the corresponding (R)-acetates and (S)-alcohols with high yields and excellent enantioselectivities (up to ee > 99%).