Ligand-accelerated reactions

There are several Ti-tartrate complexes present in the reaction system. It is believed that the species containing equal moles of Ti and tartrate is the most active catalyst. It promotes the reaction much faster than Ti(IV) tetraalkoxide alone and exhibits selective ligand-accelerated reaction.9... 

A further advantage of this ligand-accelerated reaction is that a directing functional group is not essential for enantioselectivity, as in asymmetric epoxidation and hydrogenation. Even simple alkenes are converted into diols in 20-88% ee... 

Recently, the enantioselective hydrogenation of ethyl pyruvate catalyzed by cinchona modified Pt/Al203 (ref. 1) was shown to be a ligand accelerated reaction (ref. 2). The rate of reaction for the fully modified system is more than 10 times faster than the racemic hydrogenation using unmodified catalyst. Under certain reaction conditions, this liquid phase hydrogenation exhibits a turn-over frequency of up to 50 s 1 (3.4 mol/kg-cat s). Emphasis until now has been directed at empirically increasing optical yields (ref. 3,4). 

Besides several diastereoselective heterogeneous catalytic hydrogenations [1-3] only two enantioselective hydrogenation reactions are known the reduction of p-keto-esters with Raney-nickel modified by tartaric acid and of pyruvic acid esters with Pt modified by cinchona alkaloids. Garland and Blaser [4] described the reduction of pyruvic acid ester as a "ligand-accelerated" reaction with the adsorption of the modifier new active sites are generated on the catalyst surface. On these new centers the selective reaction is faster and the increased reaction rate is accompanied by greater enantioselectivities. 

Garland, M., Blaser, H.U. (1990) A heterogeneous "Ligand-accelerated" reaction enantioselective hydrogenation of ethyl pyruvate catalysed by cinchona-modified Pt-Alumina catalysts, J. Amer. Chem. Soc., 112, 7048-7050. 

Hydrosilylations by complexed CuH have been applied to several substrate types (Scheme 1-17). As illustrated by the following examples, the stereochemical outcomes from both 1,2-additions (to aryl ketones and aryl imines ) and 1,4-conjugate additions (cyclic ketones, P-aryl and/or P-silyl enoates, and unsaturated lactones) can be controlled by these ligand-accelerated reactions. One of the key tricks to this chemistry is to take advantage of the tolerance of CuH complexes to alcohols and water.In fact, several methods rely on the presence of a bulky alcohol (e.g., t-BuOH) to significantly enhance reaction rates. It takes relatively little added alcohol (volume-wise) to accelerate the hydrosilylation, usually on the order of 1-3 equivalents. The role of this additive is usually ascribed to the more rapid quenching of an intermediate copper alkoxide or enolate, which necessarily generates a copper alkoxide, an ideal precursor to rapid reformation of CuH in the presence of excess silane. Thus, the rate increase is presumably due to... 

A number of nitrogen ligands are of natural origin. Owing to the pioneering research of Sharpless and co-workers, the cinchona alkaloids and their derivatives (67) play a fundamental role in the osmium-catalyzed dihydro lation reaction. This is a typical ligand accelerated reaction in which the chiral ligands enhance the reaction rates by a factor of 25 over the uncatalyzed reaction. 

Ruthenium tetroxide has also shown its potential as a practical catalyst in the dihydroxylation of alkenes. Unlike the isoelectronic osmium tetroxide, which catalyzes dihydroxylation via a ligand accelerated reaction, alkenes can be oxidized... 

Likewise, the influence of the ligand catalyst ratio has been investigated. Increase of this ratio up to 1.75 1 resulted in a slight improvement of the enantioselectivity of the copper(L-tryptophan)-catalysed Diels-Alder reaction. Interestingly, reducing the ligand catalyst ratio from 1 1 to 0.5 1 resulted in a drop of the enantiomeric excess from 25 to 18 % instead of the expected 12.5 %. Hence, as anticipated, ligand accelerated catalysis is operative. 

Hie process was S 2 -selective in the presence of catalytic amounts of ligands fS)-32 or Is, R, Rj-43 and CufOTf )2- Hiis is another example of ligand-accelerated catalysis without the ligand tlie reaction was much slower and proceeded witli low regioselectivity. 

Under similar conditions, employing a cationic Rh complex (10mol%) and hydrogen (1 atm), the aldehyde-enone 17 was subjected to the cycli-zation to give the cyclic aldol product 18 in 89% with czs-selectivity up to 10 1 (Scheme 19) [31]. Use of (p-CF3Ph)3P as ligand accelerated the reaction... 

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. 

It should be noted that the reaction of benzalde-hyde with (Z)-3-trimethylsiloxy-2-pentene in ethanol or dichloromethane in the presence of the chiral catalyst resulted in a much lower yield and selectivity. On the basis of these results, we propose the catalytic cycle shown in Scheme 2. The catalyst A formed from Cu(OTf)2 and a bis(oxazoline) ligand accelerates the aldol reaction to generate the intermediate B. In aqueous solvents, B is rapidly hydrolyzed to produce the aldol product C and regener-... 

Further, a comparison of the effects of ligand on enantioselectivity in the cyclo-propanation and aziridination reactions revealed a linear relationship. Jacobsen argues that this reinforces the mechanistic analogy between these group-transfer reactions and suggests that the transition states are subject to similar selectivity determining factors. Finally, Jacobsen observed ligand acceleration with the diimines in this reaction. 

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