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

Abstract

Background: 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 sol. 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. Main results: 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. Conclusions and implications: 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. [on SciFinder(R)]