Amination ruthenium-catalysed

In practice in the literature of the past 20 years the important results with ruthenium in epoxidation are those where ruthenium was demonstrated to afford epoxides with molecular oxygen as the terminal oxidant. Some examples are presented (see later). Also ruthenium complexes, because of their rich chemistry, are promising candidates for the asymmetric epoxidation of alkenes. The state of the art in the epoxidation of nonfunctionalized alkenes is namely still governed by the Jacobsen-Katsuki Mn-based system, which requires oxidants such as NaOCl and PhIO [43,44]. Most examples in ruthenium-catalysed asymmetric epoxidation known until now still require the use of expensive oxidants, such as bulky amine oxides (see later). 

The Ru(II)/ROOH system can also be used to oxidize tertiary amines. The intermediate iminium ion is formed, as described earlier for secondary amines, and can be trapped by nucleophiles. Thus, the ruthenium-catalysed oxidation of tertiary amines with hydrogen peroxide in methanol can be performed to give the corresponding a-methoxyamines with high efficiency as illustrated in Fig. 24 [ 137]. Another example is the selective demethylation of tertiary amines in methanol with a combination of Ru(II) and H202, followed by hydrolysis of the intermediate a-methoxylated amines. For example, the methoxylation of N,N-dimethyl-p-toluidine followed by treatment with 2 N HC1 solution gave N-methyl-p-toluidine in 75% yield (Eq. 35) [137]. 

Ruthenium-catalysed oxidations with dioxygen or hypochlorite are currently methods of choice for the oxidation of alcohol, ethers, amines and amides. In hydrocarbon oxidations, in contrast, ruthenium has not yet lived up to expectations. The proof of principle with regard to direct oxidation of, for example, olefins, with dioxygen via a nonradical, Mars-van Krevelen pathway has been demonstrated but this has, as yet, not led to practically viable systems with broad scope. The problem is one of rate although feasible the heterolytic oxygen-transfer pathway cannot compete effectively with the ubiquitous free-radical autoxidation. 

Hamid MHSA, Williams JMJ (2007) Ruthenium-catalysed synthesis of tertiary amines from alcohols. Tetrahedron Lett 48(47) 8263-8265... 

The ruthenium-catalysed arylation, by aryl halides, of benzylic amines carrying a pyridine coordinating group is thought to involve a concerted metallation-deprotonation pathway to give intermediates such as (96), followed by oxidative addition of the aryl halide to ruthenium and then reductive elimination. The reaction can be successM with aryl chlorides, as well as bromides and iodides, but here there are mechanistic differences. The ability of ruthenium to activate remote ring positions to electrophilic substitution has been referred to earlier, see Ref. 97. The reaction of ruthenium-coordinated 2-pyridyl arenes (51) with secondary alkyl halides has been shown to result in the formation of metfl-alkylated products. ... 

A two-step stereoselective strategy for converting glycine-derived aminoesters into unnatural cyclic amino acids has been reported. The process involves a palladium-catalysed tandem allylic amination/[2,3]-Stevens rearrangement followed by a ruthenium-catalysed ring-closing metathesis (Scheme 175). " ... 

Another useful synthesis of aldehydes and ketones involves the ruthenium catalysed amine A-oxide oxidation of alcohols. The reaction proceeds readily at room temperature and although a variety of A-oxides can be used the best yields... 

Cheng recently explored an efficient method to synthesize substituted isoquinolinium salts from the one pot ruthenium-catalysed annulation with alkynes of in situ generated aldimines, from benzaldehydes and amines. [RuCl2(p-cymene)]2/AgBF4 catalyst associated with the oxidant Cu(BF4)2.6H20 (2 equiv.) at 110°C, led to isoquinolinium salts. The postulated five-membered cationic ruthenacycle intermediate was isolated in that case [(Eq. 98)] [188]. 

Scheme 1 First chelation-assisted ruthenium-catalysed alkylation of benzyl amine derivatives...

It has been shown that the presence of catalytic amounts of carboxylic acid such as trani-l,2-cyclohexyldicarboxylic or 3,4,5-trifluorobenzoic acid improved the ruthenium-catalysed sp C-H bond alkylation of cyclic amines by terminal olefins and allowed reaching full conversion of less reactive A -pyridylpiperidine derivatives. Thus, in the absence of CO but in the presence of tra s-l,2-cyclohexyldi-carboxylic acid, the A -pyridylpiperidine 38 was efficiently hexylated into mono- 39 and dialkylated 40 piperidine derivatives, whereas in the absence of carboxylic acid... 

Scheme 32 Ruthenium-catalysed formation of cyclic amines via reactive iminium intermediates...

Scheme 35 Ruthenium-catalysed alkylation of indoles with tertiary methyl amines...

H, Cl, Br, NO2, Me, MeO) by bromamine-B, catalysed in the presence of HCl in 30% aqueous methanol by RuCls have been smdied and a biphasic Hammett a-relationship derived. A kinetic study of the ruthenium(in)-catalysed oxidation of aliphatic primary amines by sodium A-bromo-j -toluenesulfonamide (bromamine-T, BAT) in hydrochloric acid medium has been undertaken and the mechanism of the reaction discussed. A concerted hydrogen-atom transfer one-electron transfer mechanism is proposed for the ruthenium(in)-catalysed oxidation of 2-methylpentane-2,4-diol by alkaline hexacyanoferrate(III). The kinetics of the oxidation of propane-... 

The latter, on reaction with methylamine yielded via the P-epoxide 373, the trans-a aminoalcohol 374, which was N-acylated to the amide 375. Acid-catalysed dehydration of the tertiary alcohol 375, led to the olefin 375, from which the key radical precursor, the chlorothioether377 was secured in quantitative yield by reaction with N-chlorosuccinimide. In keeping with the earlier results recorded for structurally related compounds, 377 on heating in the presence of ruthenium dichloride and triphenylphosphine also underwent a 5-exo radical addition to generate the cyclohexyl radical 378 which recaptured the chlorine atom to furnish the a-chloro-c/5-hydroindolone 379. Oxidation of thioether 379 gave the corresponding sulfoxide 380, which on successive treatment with trifluoroacetic anhydride and aqueous bicarbonate led to the chloro-a-ketoamide 381. The olefin 382 resulting from base induced dehydrochlorination of 381, was reduced to the hydroxy-amine 383, which was obtained as the sole diastereoisomer... 

A second-order dependence on crotonic acid has been observed in its Os(VIII)-catalysed oxidation with CAT in alkaline solution. The reaction rate varied linearly with the concentration of Os(VIII). A mechanism has been proposed.140 The kinetics of the ruthenium(III)-catalysed oxidation of the secondary amines with CAT in acidic medium have been obtained and mechanisms have been postulated.141 Uncatalysed and Ru(III)-catalysed oxidation of ethylenediamine, diethylenetriamine, triethylenete-tramine, aminoethylpiperazine, and isophoronediamine with CAT in HC1 solution showed a fractional dependence on the amine, hydrogen ions, and Ru(III), and it is independent of CAT concentration. TSNH2CI has been postulated as the reactive species and a mechanism has been suggested.142... 

The first enantioselective alkylation of l,3-diphenylprop-2-enyl ethylcarbonate 19 with sodio dimethyl malonate using a ruthenium-based catalyst has been reported [113]. As shown in Eq. 2, a planar-chiral cyclopentadienylruthenium complex 35 catalyses the addition in excellent yield and enantioselectivity. The complex also catalyzed the amination although in lower ee (74%). Other derivatives of the complex also gave excellent results. Interesting selectivity (90-95% ee) has been obtained with platinum complexes though the conversions are low (25-39%) [114,115]. 

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