Rhodium Catalyzes The Hydrogenation Reaction Of Ketoesters

The transformation of ketones and esters to the corresponding alcohols is one of the most important chemical reactions in organic synthesis. Traditionally production of these chemicals is based on processes using stoichiomeric amounts of reducing reagents, such as LiAlH4, NaBH4 and BH3, which lead to risk in operation and tedious workup. From the viewpoint of both atom economy and practical applications, the direct catalytic hydrogenation of ketones or esters with hydrogen gas affords a clean and efficient route for the preparation of alcohols. Indeed, over the past few decades, the hydrogenation of ketones for the preparation of alcohols has achieved a great deal of success. However, for esters, the hydrogenationis still a challenging task due to their poor reactivity and selectivity. In recent years, excellent catalytic systems have been developed, which are mainly based on pincer complexes containing Fe, Co, Ru, Ir and Os, allowing for the hydrogenationof esters under much milder conditions. One of the successful examples is Takasago’s Ru-MACHO catalyst, which has been applied to the industrial hydrogenation of (R)-lactate in a large scale to produce (R)-1,2-propane diol.Diols especially 1,2-diols and 1,3-diols have become an important building blocks in various synthetic applications. It has been used as precursor and intermediates in the synthesis of active pharmaceutical ingredients, organic transformations, polymer synthesis, and among others. In the literature, diols are synthesized generally by the following methods:osmium-catalyzed dihydroxylation of olefins, diboration of olefins, hydrogenation of α-hydroxy esters and/or a-hydroxy ketones and/or 1,2-diketones, ring-opening reactions of epoxides, enzymatic reactions and the reduction of a-ketoesters with NaBH-4. Among these methods, hydrogenation with H2 is perhaps the most straightforward, efficient and atom-economic method.Considering the importance of alcohol products, we chosed the catalyzed hydrogenation of keto esters selectively to produce diols directly as our research based on Ru-MACHO catalyst. Therefore, a series of reaction conditions such as reaction time, temperature, base, H2 presure and solvents are examined. Under the optimized reaction conditions, our results demonstrated that the substrate such as a-keto esters can be hydrogenated smoothly affording high chemoselectivity on 1,2-diol or a-hydroxy esters. The chemoselectivity can be readily altered by simply varying the reaction conditions, including particularly the strength of the base. We next investigated the substrate scope of the reaction. With a strong base and a high temperature, various substituted aromatic substrates and aliphatic substrates were both hydrogenated to diol products with high isolated yields. Where a weaker base, lower H2 pressure and lower temperature were employed, the substrates were all hydrogenated to the α-hydroxy esters. Excellent yields were obtained for almost all the substrates examined. With the success on the hydrogenation of α-keto esters, the Ru-MACHO catalytic system was futher applied to the hydrogenation of β-keto esters. Our preliminary results show that β-hydroxy esters can be obtained with a high chemoselectivity under a mild reaction conditions. But for the preparation of 1,3-diols, however, an unsatisfied result was obtained due to some side reactions. Further experiments on the preparation of 1,3-diols is still ongoing in our lab.