Ruthenium -catalyzed asymmetric

Asymmetric epoxidation of olefins with ruthenium catalysts based either on chiral porphyrins or on pyridine-2,6-bisoxazoline (pybox) ligands has been reported (Scheme 6.21). Berkessel et al. reported that catalysts 27 and 28 were efficient catalysts for the enantioselective epoxidation of aryl-substituted olefins (Table 6.10) [139]. Enantioselectivities of up to 83% were obtained in the epoxidation of 1,2-dihydronaphthalene with catalyst 28 and 2,6-DCPNO. Simple olefins such as oct-l-ene reacted poorly and gave epoxides with low enantioselectivity. The use of pybox ligands in ruthenium-catalyzed asymmetric epoxidations was first reported by Nishiyama et al., who used catalyst 30 in combination with iodosyl benzene, bisacetoxyiodo benzene [PhI(OAc)2], or TBHP for the oxidation of trons-stilbene [140], In their best result, with PhI(OAc)2 as oxidant, they obtained trons-stilbene oxide in 80% yield and with 63% ee. More recently, Beller and coworkers have reexamined this catalytic system, finding that asymmetric epoxidations could be perfonned with ruthenium catalysts 29 and 30 and 30% aqueous hydrogen peroxide (Table 6.11) [141]. Development of the pybox ligand provided ruthenium complex 31, which turned out to be the most efficient catalyst for asymmetric... 

Other enantioselective reactions performed by microwave heating include asymmetric Heck reactions (Scheme 6.53 a) [109] and ruthenium-catalyzed asymmetric hydrogen-transfer processes (Scheme 6.53 b) [110]. 

RUTHENIUM-CATALYZED ASYMMETRIC TRANSFER HYDROGENTION OF ACETOPHENONE... 

A. Ruthenium Catalyzed Asymmetric Transfer Hydrogenation (ATH) TO Ketones... 

Modification of the electronic and steric properties of BINAP, BIPHEMP, and MeO-BI-PHEP led to the development of new efficient atropisomeric ligands. Although most of them are efficient for ruthenium-catalyzed asymmetric hydrogenation [3], Zhang et al. have recently reported an ortho-substituted BIPHEP ligand, o-Ph-HexaMeO-BIPHEP, for the rhodium-catalyzed asymmetric hydrogenation of cyclic enamides (Scheme 1.2) [31]. 

BINAP core-functionalized dendrimers were synthesized by Fan et al. (36), via condensation of Frechet s polybenzyl ether dendritic wedges to 5,5 -diamino-BINAP (26—28). The various generations of BINAP core-functionalized dendrimers were tested in the ruthenium-catalyzed asymmetric hydrogenation of 2-[p-(2-methyl-propyl)phenyl]acrylic acid in the presence of 80 bar H2 pressure and in a 1 1 (v/v) methanol/toluene mixture. As later generations of the in situ prepared cymeneruthe-nium chloride dendritic catalysts were used, higher activities were observed (TOF values were 6.5, 8.3, and 214 h respectively). Relative to those of the BINAP... 

Furo[3,4-7]pyridines can be prepared in a stereoselective synthesis involving a ruthenium-catalyzed asymmetric transfer hydrogenation reaction <2001TL1899>. The reaction proceeds with exceptionally high yield and ee (Equation 50). 

Ruthenium-Catalyzed Asymmetric Hydrogenation of Aromatic Ketones... 

Kuwano, R. and Kashiwahara, M. Ruthenium-catalyzed Asymmetric Hydrogenation of N-Boc-Indoles. Org. Lett. 2006, 8, 2653-2655. 

AI-ARENESULFONYL- and N-ALKYLSULFAM0YL-1,2-DIPHENYLETHYLENED1AMINE LIGANDS FOR RUTHENIUM-CATALYZED ASYMMETRIC TRANSFER HYDROGENATION... 

K. Evetraere, J.-F. Carpentier, A. Morteux, and M. Bulliard, N-Benzoyl-norephedrine derivatives as new, effident ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of functionalized ketones, Tetrahedron Asymm. 1999, 10, 4083 4086. 

M. Hennig, K. Puntener, and M. Scalone, Synthesis of ( <)- and (S)-4-hydroxy-isophorone by ruthenium-catalyzed asymmetric transfer of hydrogenation of ketoisophorone, Tetrahedron Asymm. 2000, 11, 1849-1858. 

In order to reduce the time needed to perform a complete kinetic resolution Lindner et al53 reported the use of the allylic alcohol 30 in enantiomerically enriched form rather than a racemic mixture in kinetic resolution. Thus, the kinetic resolution of 30 was performed starting from the enantiomerically enriched alcohol (R) or (S)-30 (45%) ee obtained by the ruthenium-catalyzed asymmetric reduction of 32 with the aim to reach 100 % ee in a consecutive approach. Several lipases were screened in resolving the enantiomerically enriched 30 either in the enantioselective transesterification of (<5)-30 (45% ee) using isopropenyl acetate as an acyl donor in toluene in non-aqueous medium or in the enantioselective hydrolysis of the corresponding acetate (R)-31, (45% ee) using a phosphate buffer (pH = 6) in aqueous medium. An E value of 300 was observed and the reaction was terminated after 3 h yielding (<5)-30 > 99% ee and the ester (R)-31 was recovered with 86% ee determined by capillary GC after 50 % conversion. 

BTNAP is available as either the (+)- or (- )-enaiitionier and displays broad utility in rhodium- and ruthenium-catalyzed asymmetric hydrogenations of (3-keto esters and alkenes. ... 

Girard, C., Genet, J.-P., Bulliard, M. Non-linear effects in ruthenium-catalyzed asymmetric hydrogenation with atropisomeric diphosphines. Eur. J. Org. Chem. 1999, 2937-2942. 

M. K. Tse, C. Dobler, S. Bhor, M. Klawonn, W. Magerlein, H. Hugl, M. Beller, Development of a ruthenium-catalyzed asymmetric epoxidation procedure with hydrogen peroxide as the oxidant, Angew. Chem. Int. Ed. 43, 5255-5260 (2004). 

Magee and Norton reported the direct, ruthenium catalyzed asymmetric hydrogena... 

Scheme 6.15 Ruthenium catalyzed asymmetric hydrogenation of pyrrolidinium salts.

The above catalytic systems for the asymmetric hydrogenation of quinolines are mainly iridium catalysts. In 2008, Fan and coworkers developed recyclable phos phine free chiral cationic ruthenium catalyzed asymmetric hydrogenation of qui nolines [23]. They found that the phosphine free cationic Ru/TsDPEN catalyst exhibited unprecedented reactivity and high enantioselectivity in the hydrogenation of quinolines in neat ionic liquid. The results were very excellent and enantioselec... 

Ruthenium-catalyzed asymmetric addition of alkane- or arenesulfonyl chlorides to styrenes leads to optically active suifones22,23. When this conversion is conducted under mild conditions no C —C bond is formed, however, at higher temperatures (100 =C), enantioselective asymmetric carbohalogenation of styrene with trichloromethanesulfonyl chloride (accompanied by sulfur dioxide extrusion) can be achieved with tetrachlorotris[( + )- or (—)-Diop]diruthenium. Excellent yields (up to 100%), but only low asymmetric inductions (up to 13 %), arc observed12. Similar results are obtained with carbon tetrachloride. A mechanism with radical formation w ithin the metal coordination sphere ( radicaloid ) has been proposed. 

We therefore quickly turned our attention to the ruthenium-catalyzed asymmetric transfer hydrogenation recently reported by Noyori. Without any optimization, 95% yield and 96% e.e. were obtained with 0.25 mol% catalyst and formic acid-triethylamine 5 2 azeotropic mixture (2.5 mL/g) in CH2CI2 at room temperature for 8 h (Scheme 6.17). - Apart from the high yield, enantiomeric excess, and turnover, this procedure is particularly simple to carry out. It also allows an easy recovery of the optically active amine by filtration, as its formiate salt at the end of the reaction, if needed, would offer an additional improvement in optical purity. 

Ruthenium-catalyzed asymmetric reductions of aromatic ketones 180 can be performed under microwave irradiation. Moberg [98] described this reaction using a monomode microwave reactor and ruthenium complexes 182 with enan-tiomerically pure chiral diamines 181 (Scheme 5.51). The reaction is very fast and efficient even sterically hindered tert-butylphenylketone, which is normally quite umeactive, was reduced in almost quantitative yield in 3 minutes. The enantio-selectivity was, however, lower than that obtained under standard conditions similarly to that described by Larhed [77] in the enantioselective Heck reaction between cydopentene 115 and phenyl triflate 116 (Scheme 5.33). 

Grayson MN, Krische MI, Houk KN (2015) Ruthenium-catalyzed asymmetric hydrohydrox-yalkylation of butadiene the role of the formyl hydrogen bond in stereochemical control. J Am Chem Soc 137 8838 850... 

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