Arene enantioselectivity

One example has already been encountered in the form of the binding constants in Table 3.2. These data form one of the first examples of compelling evidence for the involvement of attractive arene -arene interactions in determining the outcome of enantioselective catalysis. These attractive interactions have been frequently invoked as explanations for the observed enantioselectivities of... 

Most importantly, enantioselectivity benefits considerably from the use of water. This effect could be a result of water exerting a favourable influence on the cisoid - transoid equilibrium. Unfortunately, little is known of the factors that affect this equilibrium. Alternatively, and more likely, water enhances the efficiency of the arene - arene interactions. There is support for this observation"" . Since arene-arene interactions are held responsible for the enantioselectivify in many reactions involving chiral catalysts, we suggest that the enhancement of enantioselectivity by water might well be a general phenomenon. 

Clearly, complete understanding of solvent effects on the enantioselectivity of Lewis-acid catalysed Diels-Alder reactions has to await future studies. For a more detailed mechanistic understanding of the origins of enantioselectivity, extension of the set of solvents as well as quantitative assessment of the strength of arene - arene interactions in these solvent will be of great help. 

Arene - arene interactions are emerging as important contributors to not only the enantioselectivity of... 

Of all the work described in this thesis, this discovery is probably the most significant. Given the fact that the arene - arene interactions underlying the observed enantioselectivity of ftie Diels-Alder reactions described in Chapter 3 are also encountered in other organic reactions, we infer that, in the near future, the beneficial influence of water on enantioselectivity can also be extended to these transformations. Moreover, the fact that water can now be used as a solvent for enantioselective Lewis-add catalysed reactions facilitates mechanistic studies of these processes, because the number of equilibria that need to be considered is reduced Furthermore, knowledge and techniques from aqueous coordination chemistry can now be used directly in enantioselective catalysis. 

Also the arene-arene interactions, as encountered in Chapter 3, are partly due to hydrophobic effects, which can be ranked among enforced hydrophobic interactions. Simultaneous coordination of an aromatic oc amino acid ligand and the dienophile to the central copper(II) ion offers the possibility of a reduction of the number of water molecules involved in hydrophobic hydration, leading to a strengthening of the arene-arene interaction. Hence, hydrophobic effects can have a beneficial influence on the enantioselectivity of organic reactions. This effect is anticipated to extend well beyond the Diels-Alder reaction. 

Synthetic utility of stereoselective alkylations in natural product chemistry is exemplified by the preparation of optically active 2-arylglycine esters (38). Chirally specific a-amino acids with methoxyaryl groups attached to the a-carbon were prepared by reaction of the dimethyl ether of a chiral bis-lactam derivative with methoxy arenes. Using SnCl as the Lewis acid, enantioselectivities ranging from 65 to 95% were obtained. 

L = P(CH3)3 or CO, oxidatively add arene and alkane carbon—hydrogen bonds (181,182). Catalytic dehydrogenation of alkanes (183) and carbonylation of bensene (184) has also been observed. Iridium compounds have also been shown to catalyse hydrogenation (185) and isomerisation of unsaturated alkanes (186), hydrogen-transfer reactions, and enantioselective hydrogenation of ketones (187) and imines (188). 

E The writing has again been revised at the sentence level, streamlining the presentation, improving explanations, and updating a thousand small details. Several little-used reactions have been deleted (the alkali fusion of arene-sulfonic acids to give phenols, for instance), and a few new ones have been added (the Sharpless enantioselective epoxidation of alkene.s, for instance). 

Variation in catalyst and ligand can lead to changes in both regio- and enantio-selectivity. For example, the hydroboration of vinyl arenes such as styrene and 6-methoxy-2-vinylnaphthalene can be directed to the internal secondary borane by use of Rh(COD)2BF4 as a catalyst.166 These reactions are enantioselective in the presence of a chiral phosphorus ligand. 

Rhodium-catalyzed enantioselective hydrogenation of acctamido -cinnamic in water was also achieved using pyrphos bound to poly-acrylic acid as ligand.337 Roucoux described some Rh° nanoparticles which function as reusable hydrogenation catalyst for arene derivatives in a biphasic water-liquid system.338... 

The benzylic C-H activation has been effectively applied to the enantioselective synthesis of (+)-imperanene (Equation (16)).80 The key step was the Rh2(i -DOSP)4-catalyzed functionalization of the benzylic methyl C-H bond in arene 2. An impressive feature of this transformation was that both the carbenoid and substrate contained very electron-rich aromatic rings, which were compatible with the highly electrophilic carbenoids because they were still sterically protected. 

Scheme 3.12 Enantioselective hydrogenation of a ketone by transfer from iso-propanol catalyzed by the hydride complex RuH( 6-arene)(NH2CHPhCHPhNTs) and the amido complex Ru(r 6-arene)(NHCHPhCHPhNTs) [94].

Salzer et al. prepared a set of planar-chiral diphosphine ligands based on the arene chromium tricarbonyl backbone (Fig. 36.3) [21]. The straightforward four-step synthetic route allowed the preparation of 20 ligands of this family. These ligands were tested in Ru- and Rh-catalyzed enantioselective hydrogenation of various substrates, including the standard C=C substrates (dimethyl itaconate, methyl-2-acetamidocinnamate, methyl-2-acetamidoacrylate) as well as MEA-imine (l-(methoxymethyl)ethylidene-methylethylaniline) and ethyl pyruvate. Moderate conversions and ee-values were obtained. 

James et al. reported a case of product inhibition in the Rh-catalyzed enantioselective hydrogenation of N-phenyl benzaldehyde imine [37]. These authors were able to isolate the deactivated catalyst, and to obtain its X-ray structure, which showed, surprisingly, that it was a rhodium complex with the product bound through a rf-n-axene interaction (Scheme 44.5). More cases of inhibition via formation of metal arene complexes will be detailed in Section 44.5. 

Oxidation of silyl enol ethers. Oxidation of silyl enol ethers to a-hydroxy aldehydes or ketones is usually effected with w-chloroperbenzoic acid (6, 112). This oxidation can also be effected by epoxidation with 2-(phenylsulfonyl)-3-( p-nitrophenyl) oxaziridine in CHC1, at 25-60° followed by rearrangement to a-silyloxy carbonyl compounds, which are hydrolyzed to the a-hydroxy carbonyl compound (BujNF or H,0 + ). Yields are moderate to high. Oxidation with a chiral 2-arene-sulfonyloxaziridine shows only modest enantioselectivity. 

Ito and Katsuki (55) examined the use of chiral bipyridine (bpy) compounds as ligands in the asymmetric cyclopropanation of alkenes. Moderate diastereoselectivities and excellent enantioselectivities were observed in the cyclopropanation of vinyl arenes, Eq. 38. This catalyst system afforded very high ee values of the cis isomer. 

Ruthenium complexes are capable of catalyzing halogen atom transfer reactions to olefins. This has been illustrated in the enantioselective atom transfer reactions of alkane and arene-sulfonyl chlorides and bro-motrichloromethanes to olefins using chiral ruthenium complexes. Moderate ee s up to 40% can be achieved for these transformations [74-77]. These specific reactions are believed to follow a radical redox transfer chain process. 

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