Asymmetric ligand acceleration effects

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. 

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. 

Yang12 has effected an intramolecular asymmetric carbonyl-ene reaction between an alkene and an a-keto ester. Reaction optimization studies were performed by changing the Lewis acid, solvent, and chiral ligand. Ligand-accelerated catalysis was observed for Sc(OTf)3, Cu(OTf)2, and Zn(OTf)2 (Equation (6)). The resulting optically active m-l-hydroxyl-2-allyl esters provide an entry into multiple natural products. 

The Sharpless procedure for effecting osmium-catalyzed ligand-accelerated asymmetric dihydroxylation was utilized successfully the reaction could also be scaled up. Bis(3-methylthien-2-yl) ketone (59) was also a product in these reactions and was accompanied by an impurity whose structure has not been elucidated. Optimum yields of the dihydroxy material were obtained in dioxane-water/t-butanol-water mixtures. Use of osmium tetroxide instead of potassium osmate led to a slower reaction and increased the formation of undesired products. The material derived from synthesis revealed complete identity with the tablet degradates Any diastereomers that formed were not resolved under our chromatographic conditions. Attempted functionalization of the vicinal dihydroxy groups (acetate, acetonide, trflate) was unsuccessful and led to complex mixtures of products. 

Figand acceleration (the so-called Criegee effect) is the important feature of asymmetric dihydroxylation using cinchona ligands.193 In particular, bis-cinchona ligands provide remarkable acceleration (Scheme 48). This enables high turnover rates of the osmium catalysts. 

The first attempt to effect the asymmetric cw-dihydroxylation of olefins with osmium tetroxide was reported in 1980 by Hentges and Sharpless.54 Taking into consideration that the rate of osmium(VI) ester formation can be accelerated by nucleophilic ligands such as pyridine, Hentges and Sharpless used 1-2-(2-menthyl)-pyridine as a chiral ligand. However, the diols obtained in this way were of low enantiomeric excess (3-18% ee only). The low ee was attributed to the instability of the osmium tetroxide chiral pyridine complexes. As a result, the naturally occurring cinchona alkaloids quinine and quinidine were derived to dihydroquinine and dihydroquinidine acetate and were selected as chiral... 

The remarkable affinity of the silver ion for hahdes can be conveniently applied to accelerate the chiral palladium-catalyzed Heck reaction and other reactions. Enantioselectivity of these reactions is generally increased by addition of silver salts, and hence silver(I) compounds in combination with chiral ligands hold much promise as chiral Lewis acid catalysts for asymmetric synthesis. Employing the BINAP-silver(I) complex (8) as a chiral catalyst, the enantioselective aldol addition of tributyltin enolates (9) to aldehydes (10) has been developed." This catalyst is also effective in the promotion of enantioselective allylation, Mannich, ene, and hetero Diels-Alder reactions. 

The chemical industry as we currently know it would be markedly different without transition metal catalysts, as these play roles in a wide range of processes. The key task of a catalyst is to accelerate a reaction by effectively lowering the activation barrier for the reaction. Apart from acceleration, a catalyst may also be able to induce optical activity in an organic product if it includes a chiral ligand. The success of an asymmetric catalyst is defined by the enantiomeric excess, which is the difference in percentage yields of the major and minor enantiomers of the product. If 90% of one optical isomer forms and 10% of the other, the enantiomer excess is 80% obviously, the closer that this value is to 100% (which means stereospecificity is achieved) the better. Asymmetric synthesis in industry depends fully upon transition metals as the active site of the catalysis. 

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