著者

北村 雅人 塚本 眞幸 別所 祐紀

出版者

天然有機化合物討論会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

no.44, pp.533-538, 2002-09-01

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Asymmetric hydrogenation of -(acylamino)acrylic acid derivatives was first established by Kagan in 1971. A cationic (R,R)-DIOP-Rh complex smoothly hydrogenates an enamide substrate to give (S)- and (R)-phenylalanine derivatives in 7:93 ratio. This finding paved the way to asymmetric hydrogenation world as well as the synthesis of optically active natural and unnatural amino acids. A perfect enantioselection in the Kagan reaction was achieved by use of BINAP ligand (BINAP=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl) in 1980 although the Rh complex suffered from the high substrate specificity. A breakthrough has been made by the discovery of BINAP-Ru complexes, which serve as excellent catalyst precursors for highly enantioselective hydrogenation of a variety of functionalized prochiral olefins and ketones including enamides, ,-and ,-unsaturated carboxylic acids, allylic and homoallylic alcohols. keto esters, hydroxy ketones, and amino ketones. Interestingly, the sense of asymmetric induction in the (S)-BINAP-Ru(II)-catalyzed Kagan reaction is opposite to that observed with (S)-BINAP-Rh(I) catalysts. In this paper, we would like to focus on the mechanism of the BINAP-Rh- and -Ru-catalyzed Kagan reaction that is the origin of highly enantioselective hydrogenation. Combination of isotope labeling experiments and kinetics has revealed that the reaction proceeds via a monohydride-unsaturate mechanism involving the initial RuH formation followed by a reaction with an olefinic substrate. The major S and minor R enantiomers are produced via the same mechanism. The detail rate law analysis made it possible to determine the energy diagram of the catalytic species, which has also been experimentally substantiated by the ^<12>C/^<13>C and ^1H/^2H isotope effect measurements. The Ru monohydride species B is first generated from the diacetate A and H_2, and then forms a short-lived enamide complex C which delivers the hydride to the C(3) position. The addition of the RuH species to the olefinic bond is endergonic and reversible. The overall rate is limited by the Ru-C hydrogenolysis step of the resulting Ru-alkyl species D. The enantioselection is made during this irreversible step but actually is controlled by the relative free energies of the diastereomeric RuH/olefin complexes. Structural information was obtained by NMR studies as well as X-ray crystallographic analysis. Crystalline mono-methanol coordinated diacetate complex and the derivative of the Ru monohydride species were isolated and characterized by X-ray study. The molecular structures are consistent with those in solution estimated from NMR experiments. The reaction monitoring by NMR using ^<13>C-labeled substrates revealed that the observed Ru-enamide complex is nonproductive and that the mode of enamide coordination corresponds with that in the reactive RhH_2 intermediate in the related Rh-catalyzed hydrogenation which occurs via a unsaturate-dihydride mechanism. All of the observation strongly support the enantioface selection based on the stereo-complementary models of the enamide/metal chelate complexes.