Ligand accelerated asymmetric catalysis

Asymmetric syntheses can be carried out even more easily and elegantly than by reacting achiral substrates with enantiomerically pure chiral reagents if one allows the substrate to react with an enantiomerically pure species formed in situ from an achiral reagent and an enantiomerically pure chiral additive. The exclusive reaction of this species on the substrate implies that the reagent itself reacts substantially slower with the substrate than its adduct with the chiral additive. If high stereoselectivity is observed, it is exclusively due to the presence of the additive. The chiral additive speeds up the reaction. This is an example of ligand accelerated asymmetric catalysis. 

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. 

About a decade after the discovery of the asymmetric epoxidation described in Chapter 14.2, another exciting discovery was reported from the laboratories of Sharpless, namely the asymmetric dihydroxylation of alkenes using osmium tetroxide. Osmium tetroxide in water by itself will slowly convert alkenes into 1,2-diols, but as discovered by Criegee [15] and pointed out by Sharpless, an amine ligand accelerates the reaction (Ligand-Accelerated Catalysis [16]), and if the amine is chiral an enantioselectivity may be brought about. 

In asymmetric catalysis, Sharpless emphasized the importance of ligand-accelerated catalysis through the construction of an asymmetric catalyst from an achiral precatalyst via ligand exchange with a chiral ligand. By contrast, a dynamic combinatorial approach, where an achiral precatalyst combined with several multicomponent chiral ligands (L, -----) and several chiral activator ligands... 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

The ligand acceleration is particularly useful in catalysis with chiral ligands. Here, this phenomenon helps a stereoselective reaction mode to dominate over competing unselective pathways, leading to a highly efficient asymmetric catalysis. 

Han H, Janda KD, Soluble polymer-bound ligand-accelerated catalysis Asymmetric dihydroxylation, J. Am. Chem. Soc., 118 7632-7633, 1996. 

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

See reference 8 in Han, H. Janda, K. D., Soluble Polymer-Bound Ligand-Accelerated Catalysis Asymmetric Dihyroxylation. J. Am. Chem. Soc. 1996, 118, 1632. See also Kan, H. Janda, K. D., A Soluble Polymer-Bound Approach to the Sharpless Catalytic Asymmetric Dihydroxylation (AD) Reaction Preparation and Application of a [(DHQD)2PHAL-PEG-OMe] Ligand. Tetrahedron Lett. 1997, 38,1527. 

We dedicate a large part of this chapter to two very important, and extraordinarily useful, enantioselective methods - catalytic asymmetric epoxidation (AE) and catalytic asymmetric dihydroxylation (AD). Impressively, both these methods were developed by Professor Barry Sharpless s research group and are therefore often referred to as the Sharpless epoxidation and the Sharpless dihydroxylation. Both are examples of ligand-accelerated catalysis. 

In this section we will not consider the detailed mechanisms by which the stereochemistry of the ligand controls the stereochemistry of the product in many cases this is not known anyway. We simply want to show you how the idea of ligand-accelerated catalysis has led to the discovery of new asymmetric reactions. 

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