A Chemical-enzymatic Tandem Reaction Of Oxidation/aldol Condensation Generates Chiral ?-hydroxycarbonyl Compounds

The development of a combination enzyme and organocatalyst for aqueous phase sequential organic transformation has great significance,especially for applications in the preparation of high-added-value optically pure molecules under environmentally friendly conditions.Achieving the one-pot method in an aqueous medium is a perfect method of organic synthesis.Complex molecules can be synthesized from simple starting materials rapidly and efficiently providing maximum use of resources.Utilizing the aqueous benefits of biocatalysis,the combination of enzymes and organocatalysts in water media for the chemo-enzymatic dual-catalysis process.This article through the utilization of the bulky steric hindrance of chiral proline derivatives,an integrated laccase and proline as a chemo-enzymatic co-catalyst system is developed for aqueous phase oxidation/aldol enantioselective sequential reaction.The main research contents are described below.First part,The larger supramolecular aggregate SILs/G3/proline as a chemical catalyst for co-catalysis with laccase/TEMPO.By utilizing the large size of solvate ionic liquids around the proline molecule as shields it is reasonable to expect that a combination of laccase and proline may eliminate their mutual deactivations.The addition of the ionic liquid G₃NTf₂ to a pot reaction could further consolidate its shielding function.As we present in this study,this one-pot organic transformation,an initial laccase-mediated oxidation of arylbenzyl alcohols and cyclohexanol to form aldehydes and cyclohexanone,followed by a subsequent proline derivative-catalyzed aldol condensation of the in situ generated intermediates,provides various 1,2-diastereoisomeric chiral?-hydroxy ketones with acceptable yields(up to 91%yield)and high enantio-/diastereoselectivities(up to 99%ee and 98:2 dr).Second part,in order to expand the application range and confirm the general feasibility of the laccase,the use of a sterically hindranced proline(trans-(tert-butyldiphenylsilyloxy)-proline)instead of the SILs/G3/proline to integrate this co-catalyst system was also investigated.It was found that a combination of laccase and this catalyst as a co-catalyst system,without the additive G₃NTf₂,also presented an efficient oxidation/aldol one-pot sequential process,which was superior to that attained with a combination of laccase and supramolecular aggregate SILs/G3/proline as a co-catalyst system,from an environmental point of view,because of the nonexistence of the harmful additive G₃NTf₂.The corresponding reactions could also afford the desired1,2-diastereoisomeric chiral?-hydroxy ketones with acceptable yields(up to 89%)and high enantio-/diastereoselectivities(up to 99%ee and 98:2 dr).