Ruthenium-catalyzed oxidation

Sheldon et al. have combined a KR catalyzed by CALB with a racemization catalyzed by a Ru(II) complex in combination with TEMPO (2,2,6,6-tetramethylpi-peridine 1-oxyl free radical) [28]. They proposed that racemization involved initial ruthenium-catalyzed oxidation of the alcohol to the corresponding ketone, with TEMPO acting as a stoichiometric oxidant. The ketone was then reduced to racemic alcohol by ruthenium hydrides, which were proposed to be formed under the reaction conditions. Under these conditions, they obtained 76% yield of enantiopure 1-phenylethanol acetate at 70° after 48 hours. 

Murahashi S-I, Nakae T, Terai H, Komiya N (2008) Ruthenium-catalyzed oxidative cyana-tion of tertiary amines with molecular oxygen or hydrogen peroxide and sodium cyanide sp3 C-H bond activation and carbon-carbon bond formation. J Am Chem Soc 130 11005-11012... 

The conventional synthesis of trans-2,5-dialkyl phospholanes starting from a chiral 1,4-diol is shown in Scheme 24.1. Originally, these 1,4-diols were obtained via electrochemical Kolbe coupling of single enantiomer a-hydroxy adds [25], but this method proved to be commercially impracticable and has since been replaced by more viable biocatalytic routes [26]. Reaction of the chiral 1,4-diol with thionyl chloride followed by ruthenium-catalyzed oxidation with so-... 

Y Tsuji, T. Ohta, T. Ido, H. Minbu, and Y. Watanabe, Ruthenium-catalyzed oxidation of alcohols and catechols using t-butyl hydroperoxide, J. Organometallic Chem. 270(3), 333-341 (1984). 

L. Gosalvi, I. W. C. E. Arends, R. A. Sheldon, Selective Ruthenium-Catalyzed Oxidation Of l,2 4,5-Di-o-isopropylidene 3-D-fructopyranose and other Alcohols with NaOCl, Org. Lett. 4, (2002) 1659-1661. 

Exposure of 144 to catalytic quantities of ruthenium tetroxide, generated in situ from ruthenium trichloride and sodium periodate, produces the symmetrical lactones 145 <2000JA9558>. It is proposed that the products form as a result of the ruthenium-catalyzed oxidative cleavage of the a-diketones to produce intermediate glycols (Equation 49). 

Selective oxidation of alcohols. Primary alcohols are oxidized by this RuCL complex about 50 times as rapidly as secondary alcohols. Use of benzene as solvent is critical lor this high selectivity. Little or no reaction occurs in CH3CN, THF, or DMF. Most oxidants, if they show any selectivity, oxidize secondary alcohols more rapidly than primary ones. However, ruthenium-catalyzed oxidations with N-mcthylmorpholine N-nxide and oxidations with PCC4 proceed about three times as rapidly with primary alcohols as with secondary ones. 

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. 

The ruthenium-catalyzed oxidation of aldoses by NBS under acidic46 and basic47 conditions have been investigated. The order of reactivity of some pentoses and hexoses has been determined for their oxidation by NBS in aqueous acidic media containing Hg(II) acetate. A mechanism for the reaction has been suggested on the basis of kinetic measurements.48... 

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. 

Transition metal-catalyzed cyclizations leading to formation of a new CO bond provide a particularly useful approach to dihydrofurans . For example, a high-yielding method for the synthesis of 2,3-dihydrofurans is provided by a ruthenium-catalyzed oxidative cyclization of 4-penten-l-ols (Scheme 64) <2003CL24>. 

Fig. 4.34 A catalytic cycle for ruthenium-catalyzed oxidative cleavage of olefins.

Carbohydrate oxidations are generally performed with dioxygen in the presence of heterogeneous catalysts, such as Pd/C or Pt/C [230]. An example of homogeneous catalysis is the ruthenium-catalyzed oxidative cleavage of protected mannitol with hypochlorite (Fig. 4.77) [231]. 

Ozonolysis of tosyl derivative 295a led to the corresponding protected azonane-3,8-dione in 50% yield (Equation 41). Ruthenium-catalyzed oxidation was found to be more efficient, resulting in an increased 70% yield of the product, which is consistent with the result obtained for dialkyl-substituted systems (Scheme 32, Section 14.10.6.3) <1995J(P1)1137>. Similar ozonolysis of pyrrolo ethyl carboxylate 295c led to 75% of cyclic amino acid derivative <20010L861>. 

A successful ruthenium-catalyzed oxidative coupling and subsequent cyclization between 2-aminobenzyl alcohol and secondary alcohols in the presence of KOH and 1-dodecene leading to quinolines has been reported <03T7997>. After optimization of conditions, yields were fair to good. The reaction is widely applicable to a large series of 2-substituted quinolines. 

Table 3.2 Ruthenium-catalyzed oxidation of alcohols with oxidant...

Indeed, a transformation of alkenes to a-ketols was found to proceed highly efS-ciently. Thus, the low-valent ruthenium-catalyzed oxidation of alkenes with peracetic acid in an aqueous solution under mild conditions gives the corresponding a-ketols, which are important key structures of various biologically active compounds [127]. Typically, the RuCls-catalyzed oxidation of 3-acetoxy-1-cyclohexene (42a) and 3-azide-1-cyclohexene (42b) with peracetic acid in CH2CI2-CH3CN-H2O (1 1 1) gave (2S, 3R )-3-acetoxy-2-hydroxycyclohexanone (43a) and (2S, 3R )-3-azide-2-hydroxy-cyclohexanone (43b) chemo- and stereoselectively in 70% and 65% yield, respectively... 

Furthermore, the method can be applied to the synthesis of 4-demethoxyadriamy-cinone, which is the key structure of the anti-cancer drugs, the adriamycins such as idarubicin and aimamycin (52) (Eq. 3.69). The ruthenium-catalyzed oxidation of allyl acetate SO gives the corresponding a-hydroxyketone 51 in 60% yield (Eq. 3.69) [129]. 

The oxidation of N-methylamines provides various useful methods for organic synthesis. Selective demethylation of tertiary methylamines can be carried out by the ruthenium-catalyzed oxidation and subsequent hydrolysis (Eq. 3.71). This is the first synthetically practical method for the N-demethylation of tertiary amines. The methyl group is removed chemoselectively in the presence of various alkyl groups. 

The biomimetic construction of piperidine skeletons from N-methylhomoallyl-amines is performed by means of the ruthenium-catalyzed oxidation and subsequent olefm-iminium ion cyclization reaction. trans-l-Phenyl-3-propyl-4-chloropiper-idine 57 ivas obtained from N-methyl-N-(3-heptenyl)aniline stereoselectively via 56 upon treatment ivith a 2 N HCI solution (Eq. 3.72). This cyclization is the first demonstration of biomimetic formation of piperidine structure using N-methyl group, and can be rationalized by assuming the formation of iminium ion 58 by protonation of the oxidation product 56, subsequent elimination of f-BuOOH, nucleophilic attack of an alkene, giving a carbonium ion, which is trapped with Cl nucleophile from the less hindered side. 

Recently, a new type of reaction - that is, aerobic oxidative cyanation of tertiary amines - was discovered. In this reaction, oxidation with molecular oxygen in place of peroxides, in addition to direct carbon-carbon bond formation by trapping of the iminium ion intermediates with a carbon nucleophile under oxidative conditions, is accomplished simultaneously. The ruthenium-catalyzed oxidation of tertiary amines with molecular oxygen (1 atom) in the presence of sodium cyanide gives the corresponding a-aminonitriles (Eq. 3.74) [132], which are useful for synthesis of a-amino acids and 1,2-diamines. 

Since the Lewis acid-promoted reactions of the oxidized products with nucleophiles give the corresponding N-acyl-a-substituted amines efficiently, the present reactions provide a versatile method for selective C-H activation and C-C bond formation at the a-position of amides [138]. Typically, TiCl4-promoted reaction of a-t-butyldioxypyrrolidine 66, which can be obtained by the ruthenium-catalyzed oxidation of l-(methoxycarbonyl)pyrrolidine with f-BuOOH, with a silyl enol ether gave keto amide 67 (81%), while the similar reaction with less reactive 1,3-diene gave a-substituted amide 68 (Eq. 3.80). 

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