Ru-Catalyzed Asymmetric Hydrogenation

SCHEME 14. Selected examples of enantioselective hydrogenation of non-enamide substrates. 

SCHEME 16. Enantioselective hydrogenation of x,/3-unsaturated carboxylic acids. 

Examples and Utility. An important application of this hydrogenation is enantioselective synthesis of naproxen. This commercial anti-inflammatory agent is obtained in 97% ee under high hydrogen pressure. 

Isoquinoline Synthesis. Olefins that contain certain neutral donor functionalities are also effectively hydrogenated. Investigation of the enan-tioselective hydrogenation of enamide substrates has resulted in a general procedure for the asymmetric synthesis of isoquinoline alkaloids. 

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Scheme 5.2-10 Ru-catalyzed asymmetric hydrogenation of tiglic acid, followed by product...

Scheme 5.2-11 Ru-catalyzed asymmetric hydrogenation of isobutylatropic acid, followed by extraction of the product ibuprofen with SCCO2.

Scheme 28. Examples of Ru-catalyzed asymmetric hydrogenation reactions of /i-keto esters...

OPTICALLY ACTIVE 3-HYDROXY CARBOXYLATES OBTAINED BY (R)-BINAP-Ru-CATALYZED ASYMMETRIC HYDROGENATION OF 3-OXO CARBOXYLATES ... 

A series of non-f, -symmetrical ferrocene-based 1,5-diphosphane ligands (TaniaPhos) has been developed by Knochel.88,88a,88b The ligands have been effectively used in Rh- or Ru-catalyzed asymmetric hydrogenations. The ligand 39, which has an MeO group at the chiral carbon center, has shown excellent applications in the hydrogenation of several olefin and ketone substrates.89 Weissensteiner and Spindler have reported a series of structurally different... 

Compared to the great advance achieved in the Rh-catalyzed asymmetric hydrogenation, the Ru-catalyzed asymmetric hydrogenation of ct-dehydroamino acid derivatives takes a different mechanistic pathway,215 and little success has been made. 

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

A BINAP-Ru catalyzed asymmetric hydrogenation ofy-keto esters and o-acylbenzoic esters gives y-lactones and o-phthalides, respectively, with an excellent enantioselectivity (Scheme 1.36) [190,191], The sense of enantioselection is the same as that in the hydrogenation of a-and (3-keto esters. 

The BINAP-Ru catalyzed asymmetric hydrogenation of difunctionalized ketones is applicable to synthesis of several biologically active compounds [lc, 193,195,196]. In Figure 1.12, the stereocenter determined by the BINAP chemistry is labeled by R or S. 

Diastereoselective reduction of the chiral silyloxy ynone A with (RJt)-43 and 2-propanol predominantly gives (7R,9R)-B (Scheme 1.88) [328]. The chirality of the C9 position is controlled by the BINAP-Ru catalyzed asymmetric hydrogenation. The chiral product is a key intermediate in the synthesis of taurospongin A, a potent inhibitor of DNA polymerase 3 and HIV reverse transcriptase. 

If only variable (1) is changed, the amidocarboxylic acid Z-A in Figure 17.77 is hydrogenated in the presence of Rh(S-BINAP)(MeOH)2 BF4 to furnish N-benzoyl-/ -phenylalanine (as shown). In the presence of R u(,S- B IN A P)(() Pi v )2, however, A-benzoyl-iS-phenylalanine (not shown) is formed. This surprising effect can be attributed to the fact that Rh- and Ru-catalyzed asymmetric hydrogenation of C=C double bonds follow fundamentally different mechanisms as will soon be seen. 

Wilson RM, Jen WS, MacMillan DWC (2005) Enantioselective organocatalytic intramolecular Diels-Alder reactions. The asymmetric synthesis of solana-pyrone D. J Am Chem Soc 127 11616-11617 Xie JH, Zhou ZT, Kong WL, Zhou QL (2007) Ru-catalyzed asymmetric hydrogenation of racemic aldehydes via dynamic kinetic resolution efficient synthesis of optically active primary alcohols. J Am Chem Soc 129 1868-1869... 

S R ratio = 5 1) [22]. Yanada and Yoneda constructed the deazaflavinophane 26, which exhibits complete facial selectivity in its oxidation and reduction reactions, e.g. the reduction with NaBD to afford 27 [23], Belokon and Rozen-berg used scalemic 4-formyl-5-hydroxy[2.2]para-cyclophane (FHPC) 28 in the synthesis of a-ami-no acids (ee 45-98 %) [24], An alternative approach to FHPC was more recently reported by Hopf [25]. Other interesting advances in the area of chiral cyclophanes include the homochir-al [2.2]paracyclophane-derived amino acids 29 and 30 [26], as well as (5)-PHANEPHOS (31) [27], which has been shown to be an effective ligand for highly enantioselective Ru-catalyzed asymmetric hydrogenations of -ketoesters and... 

The synthesis of the same precursor 340 from olefinic ester 341 <1975TL2647> and 344 from 343 (Scheme 65) take advantage of the previously mentioned Sharpless asymmetric dihydroxylation and Ru-catalyzed asymmetric hydrogenation. 

Recently, four generations of chiral diphosphine BI NAP-centered dendrimers were synthesized by Fan and coworkers via the condensation of Frechet-type dendrons with fR)-5,5 -diamino-BINAP (Figure 4.3) [32, 33]. The first- to third-generation BINAP dendrimers were tested in the Ru-catalyzed asymmetric hydrogenation of 2-[p-(2-methylpropyl)phenyl]-acrylic acid in methanol toluene (1 1, v/v) at room temperature (Scheme 4.2) [32]. The size of the dendrihc wedges was... 

T.2 Enantioselective Catalysis in Ionic Liquids 241 Table 7.4 Ru-catalyzed asymmetric hydrogenation (i keto esters in ionic liquids. 

Figure 7.15 Fluoroalkylated BINAP analogs for Ru-catalyzed asymmetric hydrogenations in SCCO2.

The Ru-catalyzed asymmetric hydrogenation of racemic a-substituted cyclic ketones was applied to the synthesis of various chiral natural products and analogs, such as (-)-galanthamine [80], (-)-ALTHC [81], CP 55,940 [82], and (-)-a-lycorane [83]. 

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