Tuning lipase-catalysed kinetic resolution of 2-substituted thiophenes and furans: A scalable chemoenzymatic route to masked γ-bis-oxo-alcohols

•High demand for the development of efficient and sustainable catalytic methods to achieve enantiopure chiral building blocks is on the rise.•Herein we report a chemo-enzymatic approach where lipases were used as an alternative of great interest for this purpose.•The enzymatic strategy was applied to prepare a well-known chiral building block used to synthesize bioactive natural compounds.

The demand for greener and applicable approaches aiming at the synthesis of optically active compounds as single enantiomers has seen a significant growth worldwide. Since most of the chemically synthesized compounds are produced as racemates their kinetic resolution has been of great interest. For this purpose a number of chemo-enzymatic approaches were proposed. One of such approaches, the use of isolated lipases, is a well-established alternative. Herein we report the kinetic resolutions of 2-Substituted five-membered heteroaromatic rings. By optimizing the reaction conditions it was possible to produce (2-hydroxy)-2-substituted furans and thiophenes in high enantiomeric ratio (E > 200). Thus, racemic mixtures of compounds with slight structural differences were resolved. The current chemo-enzymatic strategy has been applied to a scalable approach leading to the formation of the enantiopure (S)-2i a well-known building block used for the synthesis of bioactive natural compounds.

Graphical abstractLipase-catalyzed kinetic resolutions of 2-Substituted five-membered heteroaromatic rings have been successfully done delivering α, β and γ-(2-hydroxy)-2-substituted furans and thiophenes in high enantiomeric ratio (E > 200). The current chemoenzymatic strategy has been applied to a scalable approach leading to the formation of the enantiopure (S)-2i a well-known building block used for the synthesis of bioactive natural compounds.Figure optionsDownload full-size imageDownload as PowerPoint slide