Ruthenium-catalyzed Epoxidations

Even though only moderate enantiomeric excess was obtained with catalyst 24, this example is of particular interest since it demonstrates how novel catalysts based on nonclassic combinations of ligands and transition metals can be discovered. 

Entry Ru-cat (amount) Oxidant Solvent Temp rq Yield (%) Ee (%) Ref. 

Nishiyama and coworkers reported that the combination of pyridine-2,6-di-carboxylic acid (H2pydic) and terpyridine ligated to mthenium(ll) resulted in a complex with reasonably high catalytic activity for the epoxidation of trans-stilbene in the presence of various high-valent iodine compounds or TBHP as terminal 

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Dioxo-ruthenium porphyrin (19) undergoes epoxidation.69 Alternatively, the complex (19) serves as the catalyst for epoxidation in the presence of pyridine A-oxide derivatives.61 It has been proposed that, under these conditions, a nms-A-oxide-coordinated (TMP)Ru(O) intermediate (20) is generated, and it rapidly epoxidizes olefins prior to its conversion to (19) (Scheme 8).61 In accordance with this proposal, the enantioselectivity of chiral dioxo ruthenium-catalyzed epoxidation is dependent on the oxidant used.55,61 In the iron porphyrin-catalyzed oxidation, an iron porphyrin-iodosylbenzene adduct has also been suggested as the active species.70... 

One of the emerging applications of 4,5-dihydroimidazole-based compounds is as chiral auxiliaries in metal complexes used for asymmetric synthesis for example, 457 in ruthenium-catalyzed DielsAlder reactions <2001 J(P 1)1500, 2006JOM(691)3445> 458 in diethylzinc addition to aldehydes <2003SL102> 459 in asymmetric intramolecular Heck reactions <20030L595> and 460 in ruthenium-catalyzed epoxidation <2005OL3393> and iridium-catalyzed hydrogenation of imines <2004TA3365>. 

Figure 7.9 Ruthenium-catalyzed epoxidations with 30% H2O2.

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... 

Oxidizing enzymes use molecular oxygen as the oxidant, but epoxidation with synthetic metalloporphyrins needs a chemical oxidant, except for one example Groves and Quinn have reported that dioxo-ruthenium porphyrin (19) catalyzes epoxidation using molecular oxygen.69 An asymmetric version of this aerobic epoxidation has been achieved by using complex (7) as the catalyst, albeit with moderate enantioselectivity (Scheme 9).53... 

The enantioseiective hydrogenation of a-amino ketones has been applied extensively to the synthesis of chiral drugs such as the / -agonist SR 58611 (Sanofi Cie). m-Chlorstyreneoxide was obtained via carbene-induced ring closure of the amino alcohol. Epoxide-opening by a chiral amine obtained via a ruthenium-catalyzed hydrogenation of an enamide has led to the desired compound where... 

Kureshy et al. have reported that ruthenium-Schiff base complexes 27 serve as a catalyst for enantioselective epoxidation of styrene derivatives (Scheme 6B.26) [71], An electronic effect similar to that described in the Mn-salen-catalyzed epoxidation (vide supra) is observed in this epoxidation, that is, an electron-donating group on the catalyst and electron-withdrawing group on the substrate lead to higher enantioselectivity. For example, the epoxidation of styrene with 27c shows modest enantioselectivity (38% ee), whereas that of m-nitrostyrene with 27a exhibits much higher enantioselectivity (80% ee). 

Another regioselective addition to an epoxide was used as one step in a synthesis of the r-butyldiphenylsilyl ether (7) of verrucarinic acid from 5.3 The diol was converted into the optically active epoxy alcohol by the Sharpless method (10, 64-65) and then oxidized to the epoxy acid 6 by the new ruthenium-catalyzed oxidation of Sharpless et al. (this volume). This epoxy acid undergoes almost exclusive / -addition with trimethylaluminum to give the desired product 7. 

Cyclic sulfates provide a useful alternative to epoxides now that it is viable to produce a chiral diol from an alkene. These cyclic compounds are prepared by reaction of the diol with thionyl chloride, followed by ruthenium-catalyzed oxidation of the sulfur (Scheme 9.26).166 This oxidation has the advantage over previous procedures because it only uses a small amount of the transition metal catalyst.167168... 

Other radical-based transformations are ruthenium-catalyzed oxidative dimerizations of phenols [263] and reductive dimerizations [264], The isomerization of chiral c/s-epoxides to tram-epoxides catalyzed by 2-10 mol% TpRu(py)2Cl proceeds at 100 °C in 95-98% yields with inversion of configuration [265], A radical or SN2 mechanism was discussed for this process. 

Tabatabaeian, K., Mamaghani, M., Mahmoodi, N.O., and Khorshidi, A. 2008. Solvent-free, ruthenium-catalyzed, regioselective ring-opening of epoxides, an efficient route to various 3-alkylated indoles. Tetrahedron Letters, 49 1450-54. 

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). 

M. Klawonn, M. K. Tse, S. Bhor, C. Ddbler, M. Beller, A convenient Ruthenium-catalyzed alkene epoxidation with hydrogen peroxide as oxidant, J. Mol. Catal. A. 218 (2004) 13. 

The ruthenium-catalyzed cyclization of epoxy iodoalkynes shows a very intriguing solvent dependence <05OL1745>. The authors rationalize this solvent dependence as a result of two different ruthenium intermediates. In a polar solvent such as DMF an iodovinylidene species is formed followed by attack of the epoxide oxygen to eventually lead to naphthalene 91 in 88% yield. A nonpolar solvent such as benzene favors the formation of a p-iodoalkyne ruthenium species. Attack of this species by the epoxide oxygen leads to formation of oxepin derivative 92 in 78% yield. 

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