Ligand acceleration effect

A stoichiometric procedure for the osmium-mediated, enantioselective aminohydrox-ylation of traws-alkenes RCH=CHR (R = Ph, Et, Pr1) has been developed employing chiral complexes between tert-butylirnidoosmium (BufN=0s03) and derivatives of cinchona alkaloids. The success of the reaction is dependent on a ligand acceleration effect corresponding diols are the by-products. The e.e. varies between 40 and 90%486,487. 

Nitrile oxides react with the methyl enol ethers of (Rs)-l -fluoro-alkyl-2-(p-tolylsulfinyl)ethanones to produce (45,5/f,/fs)-4,5-dihydroisoxazoles with high regio-and diastereo-selectivity.87 In the 1,3-dipolar cycloaddition of benzonitrile oxide with adamantane-2-thiones and 2-methyleneadamantanes, the favoured approach is syn, as predicted by the Cieplak s transition-state hyperconjugation model.88 The 1,3-dipolar cycloaddition reaction of acetonitrile oxide with bicyclo[2.2.l]hepta-2,5-diene yields two 1 1 adducts and four of six possible 2 1 adducts.89 Moderate catalytic efficiency, ligand acceleration effect, and concentration effect have been observed in the magnesium ion-mediated 1,3-dipolar cycloadditions of stable mesitonitrile oxide to allylic alcohols.90 The cycloaddition reactions of acryloyl derivatives of the Rebek imide benzoxazole with nitrile oxides are very stereoselective but show reaction rates and regioselectivities comparable to simple achiral models.91. 

Thus, in cw-vic-dihydroxylations of alkenes with 0s04 tertiary amines, like pyridine, have ligand acceleration effects (this term was introduced in Section 3.4.6, using the Sharpless epoxidation as an example). 

There is a marked rate acceleration in the presence of a tertiary amine or pyridine [19, 41]. This finding provided the background for the asymmetric dihy-droxylation (AD) and, later, the asymmetric aminohydroxylation (AA) reactions as it is this ligand acceleration effect (LAE) that ensures the reaction pathway involving the ligand. 

A kinetic study was undertaken to look at ligand acceleration effects in the AD reaction with various alkene substitution patterns. The effect is most dramatic on trisubstituted alkenes and some idea of relative reactivity can be obtained (Figure 3.4) [164]. Table 3.1 summarizes the types of simple alkenes that can be used in an AD reaction. 

Due to the ligand acceleration effect the kilC [ligand] term is larger than kg by several orders of magnitude [30], particularly at saturation (k2=k<-). Under saturation conditions, iC fligand] is also much larger than unity so that k<- does... 

In general, addition of weak acids increases the ee but the presence of water is detrimental. The modified catalyst has higher activity and a lower activation energy than unmodified Ni [10]. It is not clear yet, however, whether the enhanced rate is because of higher dispersion of the modified (corroded) Ni particles or because of a ligand acceleration effect. Note that Ni is thermodynamically unstable under ambient conditions in the presence of oxygen, a feature which complicates not only the application but also the reliable characterization of Ni catalysts. 

Another pathway is the reoxidation of the intermediate osmium(VI) to an Os (VIII) species prior to the cyclization step (Scheme 5b). Hence, the oxidation state of osmium would just change between (VIII) and (VI), which has been observed before for double bond oxidations using osmium [63]. We also needed to consider the addition of a water molecule, as it is known from the so-caUed ligand accelerating effect that osmium tetroxide can add ligands to its coordination sphere [64]. 

Historically, this distinction was first made by Heck on the basis of two different systems, one based on a simple palladium salt for aryl iodides [2] and another based on the PhsP or (2-tolyl)3P complex of palladium for aryl bromides [6-8]. However, as the performance of these initial systems was far from the levels achieved later, we cannot conclude for sure that a ligand-accelerating effect is observed in these protocols. We know today that aryl iodides and reactive aryl bromides are highly reactive practically with any form of labile palladium complex, so that the ligand-accelerating effect cannot be reliably established for these substrates in the many published protocols (type 1 and type 2 systems). 

Despite electron-rich bulky side-arms as in phosphine pincers 190,191 [245] or 192 [246] (Figure 2.24), these complexes behave strikingly different from their respective dialkyl or trialkylphosphine palladium complexes the latter complexes show t)q)e3 activtity (cf. Hartwig-Fu protocol see above). PCP-pincer complexes 190-192, however, are typical SRPCs exclusively suitable for type 1 reactions of aryl iodides and activated aryl bromides (Table 2.9, entries 1-6). Ligand-acceleration effects are not observed, which unequivocally underlines that the cleavage of these pincer complexes under the reacation conditions occurs to release nonphosphine palladium complexes with indeterminate coordination shell. 

Scheme 14.138). A ligand accelerating effect has been observed with the titanium bis (sulfonamide)imido complex. This complex can promote the reaction at room temperature with reaction rate comparable to that of its precursor, supporting the hypothesis of a catalytically active titanium imido intermediate. 

The first Lewis acid-catalyzed asymmetric Michael addition in water was developed by Kobayashi et al, who reported ee s up to 83%. Very recent developments show great promise for further improvement of Michael addition reactions in water. In an elegant study, Kaneda and coworkers used montmorillonite-enwrapped metal triflates to execute C—C bond forming Michael additions. When scandium triflate was employed, adducts were obtained in quantitative yield within a 0.5-3 h at or slightly above room temperature. The catalysts were reusable with no appreciable loss in activity.In another recent study, Lind-strdm and coworkers observed a remarkable ligand acceleration effect in aqueous ytterbium triflate-catalyzed Michael additions. A number of 1,2-diamines and 1,2-aminoalcohols were shown to have a positive influence on the rate of the reaction, the most efficient being tetramethylethylenediamine, which induced a nearly 20-fold rate acceleration. 

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