Ligand-accelerated

In summary, ligands tend to diminish the affinity of the substrate for the Lewis-acid catalyst as well as the extent of activation by this catalyst, once the ternary complex is formed. Only a few examples of ligand-accelerated catalysis " have been described... 

In summary, for the most active of catalysts, the copper(II) ion, the diamine ligands that were investigated seriously hamper catalysis mainly by decreasing the efficiency of coordination of the dienophile. With exception of the somewhat deviant behaviour of N,N -dimethylethylenediamine, this conclusion also applies to catalysis by Ni" ions. Hence, significant ligand-accelerated catalysis using the diamine ligands appears not to be feasible. 

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 first effect has been exploited in numerous ligand-accelerated [30], enantioselective 1,2-additions of RyZn reagents to aldeliydes [26]. Dimetliylzinc, for example, has a linear structure and is not reactive towards aldehydes or ketones. Upon coordination of triazine, however, a tetraliedral configuration is produced at tlie zinc... 

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. 

Lawesson s reagent 475 f., 738, 742, 746, 752 Lederle 562 lepicidin aglycon 595 f. ligand-accelerated catalysis 681 f. lignane 95... 

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... 

In 1988, Sharpless and co-workers reported that dihydroxylation was catalytically effected, with good enantioselectivity and remarkable ligand acceleration, when DHQD or DHQ p-chlorobenzoate... 

The 1,2-diol is liberated easily from cyclic osmate ester by either reductive or oxidative hydrolysis.213 Importantly, the ligand acceleration has been utilized extensively for the production of chiral 1,2-diols from (achiral) olefins using optically active amine bases (such as L = dihydroquinidine, dihydroquinine and various chiral diamine ligands).215... 

As to most chiral atropisomeric ligand, resolution or asymmetric synthesis is requisite. Mikami developed a novel ligand-accelerated catalyst. The chirality of atropos, but achiral triphos ligand-Ru complex, can be controlled by chiral diamines. Using ( -dm-dabn as controller, the single diastereomeric triphos-Ru complex was achieved through isomerization of (i )-triphos-Ru complex in dichloroethane at 80 °G (Scheme l).44... 

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. 

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... 

As mentioned in Chapter 1, ligand-accelerated catalysis occurs when a more effective chiral catalyst is obtained by replacing an achiral ligand with a chiral one. Mikami et al.89 reported a different phenomenon in which a more active catalyst was formed by combining an achiral pre-catalyst with several chiral ligands. They found that the most active and enantioselective chiral catalyst was formed in preference to other possible ligand combinations (Scheme 8 43). 

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-... 

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... 

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. 

As a result of the catalytic center-chiral entity interaction the reaction rate accelerates substantially. This phenomenon was described for the first time by Sharpless [6], who coined the term ligand accelerated catalysis. Unfortunately, the reasons for this phenomenon are still not well... 

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