Ru-catalyzed Highly Selective Asymmetric Hydrogenation Of Multifunctionalized Poly-carbonyl Ketones

In this dissertation, we actualized the highly chemo-and enantioselectivehydrogenation of some poly-functionalized ketones with Ru-SunPhos complexes. Themain contents fall into three sections:1. Upon comparing the hydrogenation rates of various β-ketocarboxylic acidderivatives, β-ketoamides were found to be hydrogenated slightly faster thanβ-ketoesters in EtOH. In THF, the rate differences were enormously increased thatβ-ketoamides were hydrogenated smoothly while β-ketoesters almost intact. Based onthese findings, a series of3-oxoglutaric acid derived with ester and amide moieties onthe two ends were hydrogenated to3-hydroxyl products with high enantioselectivities（up to98.1%ee）. Unconventional solvent and substituent effects were also discoveredwhen these substrates were hydrogenated smoothly in uncommon solvents such asTHF, CH₂Cl₂, acetone and dioxane with high enantioselectivities. Possible catalyticcycle through an enol intermediate was proposed to explain the different reactivity ofthese1,3,5-tricarbonyl substrates in the tested solvents. More pronounced solventeffects were discovered concerning the substituted substrates: ee’s increased from ca.20%in EtOH or THF to90%in acetone; inversion of products’ configurations wereobserved when the solvent was changed from EtOH to THF or acetone; and mixedsolvent systems can give better enantioselectivities than a single solvent.2. By screening the derivative moieties of3,5-diketo hexanoic acid, diethylamides were found to be hydrogenated smoothly at the C3-carbonyl with highenantioselectivities in THF, based on which we achieved a general hydrogenationmethod for the C3-selective reduction of3,5-diketo amides （26examples, up to97.4%ee and100%chemoselectivity）. The heteroatoms on the6-positions lead to partial orcomplete hydrogenation of the C5-carbonyls. Moreover, we also found that acidicadditives like BF₃·Et₂O, HBF4, H₂SO₄and TsOH·H₂O promoted the3,5-doublehydrogenation in favour of the syn-isomers. By employing ligands with opposite configurations or different types of solvents, the syn and anti selectivity werecontrolled efficiently. In the best cases, the syn:anti ratio was up to90:10and the eevalues of syn isomers were>99%.3. Upon reinvestigation into the unusual effect of C6-heteroatom on thechemoselectivity in the hydrogenation of3,5-diketoamides, we found the “activation”of the central carbonyls in1,3-diketones. The heteroatoms （O, S, N, halogens）substituted1,3-diketones were hydrogenated selectively at the carbonyls adjacent tothe heteroatoms in THF with high level of chemo-and enantioselectivity.2,4-Diketoacid esters and amides were also hydrogenated selectively at C2-carbonyls with goodchemoselectivity and moderate enantioselectivity.In summary, the coordinating ligands or solvents played some roles inmodulating the coordination environment of the target carbonyls in the asymmetrichydrogenation of polycarbonyl substrates. Therefore, it is possible to enhance thechemo-and enantioselectivity in hydrogenation of polycarbonyl compounds.