Asymmetric cascade reaction of 2-nitrophenylpyruvates over chirally modified platinum catalyst

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We developed the first heterogeneous catalytic asymmetric cascade reaction for the efficient synthesis of hydroquinolone derivatives starting from 2-nitrophenylpyruvates using supported Pt catalysts modified by cinchona alkaloids, in which we obtained high yields and good enantioselectivities. It was shown that the cascade leading to these products started with the enantioselective hydrogenation of the activated keto group, followed by the reduction of the nitro group and finally the intramolecular amidation, all steps occurring on the Pt surface. We found that tuning the reaction conditions has a major influence on the product composition, as the enantioselective hydrogenation and the reduction of the nitro group are competing reactions. Substituents on the aromatic ring have important influence on the hydroquinolone yields, which was explained by their effect on the reduction rate of the nitro group. It was demonstrated, that the final cyclization step of the cascade reaction occurs on the catalyst, i.e. metal surface. We have investigated the possibility of carrying out the reaction in continuous-flow hydrogenation system. However, the high selectivities and enantioselectivities of the main (R)-3-hydroxy-3,4-dihydroquinolin-2(1H)-one products obtained in batch reactor were not achieved, due to perturbed rate balance of the first two competitive steps. Pre-modification of the Pt/Al2O3 catalyst with the cinchona modifier enhanced the product selectivity, whereas recirculation of the product mixture besides increasing the conversion and selectivity, didn’t cause a drastic change in ee. Finally, the heterogeneous cascade reaction disclosed here is a novel application of the Orito reaction and could also be a starting point for developing attractive strategies for the synthesis of various optically pure N-heterocyclic compounds.

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