Ru-catalyzed mechanochemical asymmetric transfer hydrogenations in aqueous media using chitosan as chirality source

As the demand for sustainable methods increases, synthetic chemistry is focusing on the application of environmentally benign methods, such as fast reactions induced by alternative energy transmission. Chitosan is a chiral biopolymer of natural origin, which can be used in asymmetric catalysis. The application of Ru-chitosan complexes along with the mechanochemical activation may open great opportunities for sustainable preparation of optically pure alcohols. In the present study, we optimized the mechanochemical asymmetric transfer hydrogenation of 4-chromanone, carried out in a mixing mill. The reaction was catalyzed by the in situ formed Ru-chitosan complex, applying HCOONa as the hydrogen donor in aqueous media. We examined the mechanical effects of different grinding media sizes, then explored the scope of the system using 24 prochiral ketones, which ranged from hetero- and carbocyclic ketones to acetophenone derivatives. In most of the cases, the reactions were successfully scaled up to 1 mmol and the products were isolated in good yields and outstanding enantioselectivities. Our present study is a significant step forward to the development of environmentally benign and sustainable enantioselective processes, as the alternative activation method provided optically enriched alcohols using a biodegradable chirality source in aqueous media.