Cymene-ruthenium catalysts

DKR of secondary alcohols with cymene-ruthenium catalyst 3... 

We discovered that cymene-ruthenium catalysts 3a-c were effective catalyst systems for facile DKR of secondary alcohols at 40 °C. This catalyst system was particularly useful for the DKR of allylic alcohols [18], which underwent smoothly at room temperature to provide the corresponding chiral acetates with excellent optical purities (Scheme 1.16). This work has for the first time demonstrated that DKR can be performed at room temperature. 

Scheme 4.6 DKR of allylic alcohols with cymene ruthenium catalysts.

The (5 )-selective DKR of alcohols with subtilisin was also possible in ionic liquid at room temperature (Table 14). " In this case, the cymene-ruthenium complex 3 was used as the racemization catalyst. In general, the optical purities of (5 )-esters were lower than those of (R)-esters described in Table 5. 

The asymmetric synthesis of allenes via enantioselective hydrogenation of ketones with ruthenium(II) catalyst was reported by Malacria and co-workers (Scheme 4.11) [15, 16]. The ketone 46 was hydrogenated in the presence of iPrOH, KOH and 5 mol% of a chiral ruthenium catalyst, prepared from [(p-cymene) RuC12]2 and (S,S)-TsDPEN (2 equiv./Ru), to afford 47 in 75% yield with 95% ee. The alcohol 47 was converted into the corresponding chiral allene 48 (>95% ee) by the reaction of the corresponding mesylate with MeCu(CN)MgBr. A phosphine oxide derivative of the allenediyne 48 was proved to be a substrate for a cobalt-mediated [2 + 2+ 2] cycloaddition. 

The synthesis of a ruthenium catalyst in a one step procedure is shown in Figure 1.8. A dimer complex of cymene, i.e., 4-iso-propyltoluene) and RuC is reacted under inert atmosphere with tricyclohexylphosphine and 3,3-diphenylcyclopropene in benzene... 

Ruthenium porphyrins are effective catalysts for the cyclization of A-tosylhydrazones via intramolecular carbenoid C-H insertion to afford azetidin-2-ones <2003OL2535, 2003TL1445>. A non-porphyrin-based ruthenium catalyst, [RuCl2(/>-cymene)]2, has been developed recently for catalytic carbenoid transformation <20050L1081>. A [RuCl2(/>-cymene)]2-catalyzed stereoselective cyclization of a-diazoacetamides 418 by intramolecular C-H insertion produced azetidin-2-ones 419 in excellent yields and excellent (>99%) air-stereoselectivity (Equation 168). 

Very recently, new ruthenium catalysts, for example RuCl2(triazol-5-ylidene) (p-cymene) [11] and the catalytic system generated in situ from [RuCl2(p-cym-ene)]2, tris(p-chlorophenyl)phosphine, and 4-dimethylaminopyridine [12], have provided efficient catalysts for synthesis of the same type of enol ester. The regio-selective cyclization of acetylenic acids containing a terminal triple bond to give unsaturated lactones was performed in the presence of catalytic amounts of Ru(tris(pyrazolyl)borate)(PhC=C(Ph)C CPh)(PMe2iPr2) [13],... 

Ethyl 4-chloro-3-hydroxybutyrate (EHCB) is an important intermediate in the production of l-camitine and the cholesterol-lowering Pfizer drug Lipitor (see Chapter 31). The ruthenium catalyst, [Ru(p-cymene)I((S)-TMBTP)]+E, has been reported to reduce ethyl 3-chlorobutyrate in 97% ee with S/C ratios of 20,000 (Scheme 12.48).87,157 This chemistry has been reported at scales >100 kg.87... 

From 1995 to 2000, catalyst profiles of several ruthenium catalysts bearing pyridine-diimide 1 [13], diiminocarbene 2 [14], diamine-arene 3 [15],phos-phino-arene 4 [16], and substituted cyclopentadienyl 5 and 6 [17, 18] were shown to have good activity for the cydopropanation (Fig. 1). At the relatively high reaction temperature of 60-100 °C,they also gave moderate-to-high yields over 90%. It is interesting in that the dipyridine-diimide complex 1 and the p-cymene-carbene complex 2 show high trans selectivity, 86 14 and 82 18, respectively. 

It should be noted that while enyne metathesis is considered incompatible with molybdenum catalyst 1, ruthenium catalysts other than the Grubbs type also promote the reaction. Semeril et al. [103] reported efficient enyne RCM with a catalyst conveniently generated in situ from [RuCl2(p-cymene)]2,1,3-bis(mesityl)imidazolium chloride and caesium carbonate. Interestingly the authors found that the in situ derived system gave better results than the isolated catalyst. One of the most impressive examples of the use of enyne RCM is the total synthesis of (-)-longithorone by Layton et al. [104]. Inspired by a pro-... 

The intramolecular addition of a hydroxy group to a triple bond has been performed successfully in the presence of RuCl2(PPh3)(p-cymene) as catalyst precursor under mild conditions [18, 19]. The Lewis acid property of the ruthenium active species provides the activation of the triple bond and the Markovnikov addition of the hydroxy group to form 2-methylfuran derivatives after 1,5-proton shift and aromatiza-tion (Scheme 8.8). 

Recently, new types of ruthenium catalyst precursors that perform the Markovnikov addition of carboxylic acids to terminal alkynes have been developed. The most representative examples are [RuCl2(p-cymene)]2/P(furyl)3/base [50], Ru-vinylidene complexes such as RuCl2(PCy3)2(=C=CHt-Bu), RuCl2(PCy3)(bis(mesityl)imidazolyli-dene)(=C=CHf-Bu), [RuCl(L)2(=C=CHt-Bu)]BF4 [51], and the ruthenium complexes shown in Figure 8.1 [52-54]. 

Other ruthenium catalysts that have been used for the hydrogenation of arenes include the water-soluble and IL soluble complex Ru(ri - CioHi4)(pta)Cl2(pta = 1,3,5-triaza-7-phosphaadamantane) [37]. Comparisons were made between the catalytic activity in water and tetrafluoroborate ILs including ones contaminated with chloride, and again, in the chloride-free ILs catalytic activity is highest The related ruthenium catalyst, [Ru(q -p-cymene)(ri -triphos)Cl][PF 5] [triphos = l,l,l-tris(di-phenylphosphinomethyl)ethane] has also been shown to hydrogenate arene substrates [39]. The activity of the catalyst was compared in [BMIM][BF4] and di-chloromethane and was foimd to be considerably more active in the IL For example, in the hydrogenation of benzene to cyclohexane the TOF is 477 mol mol h when... 

The first ruthenium catalyst able to polymerize DCPD (Scheme 1) was 1 [7], which was easily accessible from [Ru(p-Cymene)Cl2] and P(Cy)s (Cy=cyclohexyl). 

The group also found that cymene ruthenium complexes, depicted in Scheme 4.6, were also active for the racemisation of alcohols in the presence of TEA. As shown in Scheme 4.6, a noticeable feature of these catalysts was their high activity towards allylic alcohols, since their DKR was possible even at room temperature by using PS-C and p-chlorophenyl acetate as the acyl donor. 

In addition, the activated hydride form of a cymene ruthenium complex was shown to be elfective as a racemising catalyst in ionic liquids such as... 

Allyl amines and alkynes were explored as starting materials for pyridines synthesis by Jun and coworkers as well [109]. The reaction proceeded through a sequential Cu(II)-promoted dehydrogenation of the allylamine and Rh(III)-catalyzed iV-annulation of the resulting a,/3-unsaturated imine and alkyne. Moderate to good yields of pyridines can be isolated (Scheme 3.52). This transformation was later on explored with ruthenium catalyst [110]. In the presence of [ RuCl2(p-cymene) 2] (0.1 equiv.), KPFe (0.1 equiv.), and Cu(OAc)2 (1 equiv.) in tAmOH at 100°C, the desired pyridine derivatives were formed in good yields. In this case, the reaction started with C-H activation and then insertion to alkynes which is different from the rhodium catalyzed case. 

Crochet, R, Diez, J., Fernandez-Zumel, M.A. and Gimeno, J., Catalytic isomerization of allylic alcohols by p cymene)-ruthenium(ll) complexes in organic and aqueous media a new recyclable and highly efficient catalyst in water containing ammonium-functionalized ligands, Adv. Synth. Catal., 2006,348,93— 100. 

In their paper describing the direct hydroxylation of arene sp C—H bonds with a ruthenium catalyst, Rao and co-workers demonstrated that a simple thiophene was also compatible with these reaction conditions (Scheme 10.21). It is proposed that under acidic conditions, [RuCl2(p-cymene)]2 facilitates C—H bond cleavage of 67 via an orthometalation process throngh chelation with the ester carbonyl group (kinetic isotope experiments also support a kinetically relevant C—H metalation step). Snbseqnent reductive elimination afforded the hydroxylated thiophene 68 in 41% yield. 

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