Cinchona alkaloid ligand

Enantioselective c -dihydroxylation of olefins using osmium catalyst in the presence of cinchona alkaloid ligands. 

L is the optically active Sharpless cinchona alkaloid ligand. c Dis = CH(SiMe3)2. 

Bis-hydroxylation. Molecular oxygen or air was used as the terminal oxidant in the osmium-catalyzed oxidation of alkenes to form cis-diols with high conversions at low catalyst amount.1298 In a triple catalytic system using H2O2 as the terminal oxidant, a cinchona alkaloid ligand has a dual function—it provides stereocontrol and acts as reoxidant via its IV-oxide. The formation of the latter is catalyzed by a biomimetic flavin component.1299... 

Recent developments in the understanding of the mechanisms of catalytic and asymmetric dihydroxylation reactions are discussed in Section V,E,l,b. An important aspect of this work is the kinetics and thermodynamics of the formation of adducts with N heterocycles, which have an important role in promoting many reactions. The crystal structure of the [0s04] adduct with the cinchona alkaloid ligand (dimethyl-... 

To improve the position selectivity in the AD of oligoprenyl compounds bis-cinchona alkaloid ligand 8 was introduced by Corey 15,6]. Its design was based on the [3+2]-cycloaddition model for the AD mechanism, which will be discussed in Section 6E. 1.2. The two 4-heptyl ether substituents of the quinolines are supposed to assist fixation of the substrate in the binding cleft. Additionally, the jV-methylquinuclidinium unit and the linking naphthopyridazine were introduced to rigidify the osmium tetroxide complex of 8 [6],... 

Most remarkably, catalytic aminohydroxylation of cinnamate amides with sulfonamides in the absence of cinchona alkaloid ligands showed a remarkable chemoselectivity in favor of amino alcohol formation [75]. 

Figure 7.1 Two Cinchona alkaloid ligands (DHQD)2-PHAL and (DHQ)2-PHAL.

Canali, L., Song, C. E. and Sherrington, D. C. Polymer-supported bis-cinchona alkaloid ligands for asymmetric dihydroxylation of alkenes - a cautionary tale. Tetrahedron Asymmetry, 1998, 9, 1029-1034. 

Keywords Asymmetric dihydroxylation, Osmium tetroxide, Cinchona alkaloid, Ligand-accelerated catalysis, Immobilization... 

However, since the catalytic system is homogenous, carefully adjusted reaction conditions were needed to circumvent the second nonselective catalytic cycle. Slow addition of the alkene and the hydrogen peroxide was necessary to obtain good enantioselectivities (Table 6) [13]. Recently, Backvall s group reported that the Cinchona alkaloid ligand participated in the reoxidation process and took the role of NMO in the catalytic cycle [15]. Versions of the triple catalytic system with vanadyl acetylacetonate replacing the flavin analogue [16] or m-CPBA as the terminal oxidant [17] have been developed and successfully applied to racemic dihydroxylation reactions. 

Solid-supported ligands provide an easy means of recycling the expensive Cinchona alkaloids. Until now, the immobilized Cinchona alkaloid ligands used in the AA process have been attached to different solid supports at the DHQ or DHQD moiety. 

A frequently observed side reaction in the AA process is the formation of the diol instead of the aminoalcohol. Generally, the Cinchona alkaloid ligands have a beneficial effect on the chemoselectivity of the AA. However, some examples of AAs producing a considerable amount of diol have been reported in the literature [40,54,55]. 

Though the mechanism of even the simple reaction of osmium tetroxide with an olefin remains uncertain, there has been considerable controversy over the mechanism of the process when a chiral cinchona alkaloid ligand is also involved . K.B. Sharpless et al., J. Org. Chem. 1996, <57, 7978. 

The asymmetric dihydroxylation is one of the simplest catalytic asymmetric processes to perform. The reaction is completely insensitive to water and oxygen and is performed in an open vessel in the range 0-25 °C. The activity of the catalyst is very good so that only 0.2-0.4% is commonly used. There is only weak product inhibition of the reaction so that high substrate concentrations e.g. 2 M) give excellent results. The cinchona alkaloid ligand is easily recovered and reused. 

Arrington, M. P., Bennani, Y. L., Gobel, T., Walsh, P., Zhao, S. H., Sharpless, K. B. Modified cinchona alkaloid ligands improved selectivities in the osmium tetroxide catalyzed asymmetric dihydroxylation (AD) of terminal olefins. Tetrahedron Lett. 1993, 34, 7375-7378. 

Corey, E. J., Noe, M. C., Lin, S. A mechanistically designed bis-cinchona alkaloid ligand allows position- and enantioselective dihydroxylation offarnesol and other oligoprenyl derivatives at the terminal isopropylidene unit. Tetrahedron Lett. 1995, 36, 8741-8744. 

Lohray, B. B., Singh, S. K., Bhushan, V. A mechanistically designed cinchona alkaloid ligand in the osmium catalyzed asymmetric dihydroxylation of alkenes. Indian J. Chem., Sect. B 2002, 41B, 1226-1233. 

Aminohydroxylations. Several carbamates HjNCOOR (R = Et, t-Bu, CljCI ), the corresponding A-chloro-iV-sodio derivatives, and A-bromoacetamide have been employed as nitrogen source in the reaction mediated by bis-cinchona alkaloid ligand complexed osmate. The products are readily manipulated to give two pairs of chiral diamines. In one version the cinchona alkaloid derivatives are linked to silica gel surface through thiopropyl chains. ... 

Figure 12.2 Impact of side chain modification on stereocontrol of cinchona alkaloid ligands and catalysts.

Catalytic asymmetric aminohydroxylation using Os(VIII) and Sharpless cinchona alkaloid ligand has been applied to a,p- and P,Y-unsaturated phosphonate substrates (Scheme 48). The reaction only works for the aryl substituted examples (287) and although initial e.e. s are sometimes low, they can be increased to >90% by a single recrystallisation. The phosphonic acid analogue... 

But matters were really significantly improved by Chen et al.52 If one cinchona alkaloid works, what about the double cinchona alkaloid ligands that are used in the asymmetric dihydroxylation reactions Amazingly, these ligands work really well for desymmetrisations of anhydrides such as 230. Only 5% of catalyst is needed and they can be done at room temperature or 20 °C for better enantiomeric excess. Once again a range of anhydrides can be used 232-234. 

Fig. 6. Summary of different features in cinchona alkaloid ligands and their effect on osmium tetroxide binding and ligand acceleration...

A member of the new ligand class for the asymmetric dihydroxylation is the bis(dihydroquinidine) ether of l,4-dihydroxy-9,10-anthraquinone. Cinchona alkaloid ligands bound to soluble polymer supports" are effective catalysts for asymmetric dihydroxylation. 

L is the optically active Sharpless cinchona alkaloid ligand. 

Recycling of Osmium by Immobilization of Osmium Tetroxide. Several groups have been actively searching for immobilized forms of osmium tetroxide in order to overcome the problems of toxicity and volatility associated with this reagent. The following are some representative examples of immobilization methods for a catalytic system (OSO4 and/or cinchona alkaloid ligand). 

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