Multi-step enzyme-organocatalyst C–C bond forming reactions in deep-eutectic-solvents: towards improved performances by organocatalyst design

Abstract

Deep eutectic solvents (DES) have recently emerged as promising non-hazardous environmentally-friendly solvents. In this respect, the use of DES as media for multi-step enzyme-organocatalysis (C–C bond formation via aldol-type reactions) represents a promising sustainable option. Being soluble in DES, organocatalysts may be retained in the DES phase during biphasic extractive work-up (e.g. with biogenic 2-methyl-tetrahydrofuran), enabling product recovery and organocatalyst recycling within the DES phase simultaneously. Herein, the proof-of-concept of designing organocatalysts—sspecifically tailored for DES—that may be properly retained in the DES phase (immobilized) among extractive cycles is demonstrated for the first time. To this end, the incorporation of novel hydrogen-bond donor groups (e.g. −OH) in the organocatalyst structure appears as a promising option to achieve improved results, leading to 1.5-fold higher conversions and yields, together with excellent chemoselectivities (>90%) for the new organocatalyst. Reactions are conducted using different bio-based DES, showing the broad applicability and possibilities that these processes may have. In this work it is demonstrated that organocatalysts can be tuned to be used in different DES. This first proof-of-concept may trigger new research and applications of DES as sustainable solvents for enantioselective C–C bond forming reactions, whereby the organocatalyst design can play an important role for optimized integrated process set-up.