Laccase‐mediated Oxidations of Propargylic Alcohols. Application in the Deracemization of 1‐arylprop‐2‐yn‐1‐ols in Combination with Alcohol Dehydrogenases

• Published in: ChemCatChem 2020-01, Vol.12 (2), p.520-527
• Main Authors: González‐Granda, Sergio, Méndez‐Sánchez, Daniel, Lavandera, Iván, Gotor‐Fernández, Vicente
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohol dehydrogenase; Bioreduction; Dehydrogenases; Deracemization; E coli; Enantiomers; Ketones; Laccase; Laccases; Organic chemistry; Oxidation; Oxidizing agents; Propargylic alcohols; Stereoselectivity
• ISSN: 1867-3880; 1867-3899
• DOI: 10.1002/cctc.201901543

The catalytic system composed by the laccase from Trametes versicolor and the oxy‐radical TEMPO has been successfully applied in the sustainable oxidation of fourteen propargylic alcohols. The corresponding propargylic ketones were obtained in most cases in quantitative conversions (87–>99 % yield), demonstrating the efficiency of the chemoenzymatic methodology in comparison with traditional chemical oxidants, which usually lead to problems associated with the formation of by‐products. Also, the stereoselective reduction of propargylic ketones was studied using alcohol dehydrogenases such as the one from Ralstonia species overexpressed in E. coli or the commercially available evo‐1.1.200, allowing the access to both alcohol enantiomers mostly with complete conversions and variable selectivities depending on the aromatic pattern substitution (97–>99 % ee). To demonstrate the compatibility of the laccase‐mediated oxidation and the alcohol dehydrogenase‐catalyzed bioreduction, a deracemization strategy starting from the racemic compounds was developed through a sequential one‐pot two‐step process, obtaining a selection of (S)‐ or (R)‐1‐arylprop‐2‐yn‐1‐ols with excellent yields (>98 %) and selectivities (>98 % ee) depending on the alcohol dehydrogenase employed. A mild and general oxidation of propargylic alcohols has been described using the catalytic system composed by the laccase from Trametes versicolor and the oxy‐radical TEMPO. Stereoselective bioreduction of the corresponding ynones using alcohol dehydrogenases has allowed the development of an efficient deracemization strategy towards the production of (S) and (R)‐alcohols with excellent selectivity.