Enantiomeric products, reaction

Most enzyme-catalyzed processes, such as the examples just discussed, are highly enantioselective, leading to products of high enantiomeric purity. Reactions with other chiral reagents exhibit a wide range of enantioselectivity. A fiequent objective of the smdy... 

Reaction of a racemic acid with an achiral alcohol such as methanol yields a racemic mixture of mirror-image (enantiomeric) products. 

The reaction discussed in the previous section involves addition to an achiral alkene and forms an optically inactive, racemic mixture of the two enantiomeric products. What would happen, though, if we were to carry out the reaction on a single enantiomer of a chiral reactant For example, what stereochemical result would be obtained from addition of H2O to a chiral alkene, such as... 

Several approaches to enantioselective synthesis have been taken, but the most efficient are those that use chiral catalysts to temporarily hold a substrate molecule in an unsymmetrical environment—exactly the same strategy that nature uses when catalyzing reactions with chiral enzymes. While in that unsymmetrical environment, the substrate may be more open to reaction on one side than on another, leading to an excess of one enantiomeric product over another. As an analog)7, think about picking up a coffee mug in your... 

Substrate and product inhibitions analyses involved considerations of competitive, uncompetitive, non-competitive and mixed inhibition models. The kinetic studies of the enantiomeric hydrolysis reaction in the membrane reactor included inhibition effects by substrate (ibuprofen ester) and product (2-ethoxyethanol) while varying substrate concentration (5-50 mmol-I ). The initial reaction rate obtained from experimental data was used in the primary (Hanes-Woolf plot) and secondary plots (1/Vmax versus inhibitor concentration), which gave estimates of substrate inhibition (K[s) and product inhibition constants (A jp). The inhibitor constant (K[s or K[v) is a measure of enzyme-inhibitor affinity. It is the dissociation constant of the enzyme-inhibitor complex. 

Figure 1.1 Energy diagram for an enzyme-catalyzed enantioselective reaction. E = enzyme A and B = enantiomeric substrates P and Q = enantiomeric products [EA] and [EB] = enzyme-substrate complexes AAC = difference in free energy denotes a transition state.

For successful DKR two reactions an in situ racemization (krac) and kinetic resolution [k(R) k(S)] must be carefully chosen. The detailed description of all parameters can be found in the literature [26], but in all cases, the racemization reaction must be much faster than the kinetic resolution. It is also important to note that both reactions must proceed under identical conditions. This methodology is highly attractive because the enantiomeric excess of the product is often higher than in the original kinetic resolution. Moreover, the work-up of the reaction is simpler since in an ideal case only the desired enantiomeric product is present in the reaction mixture. This concept is used for preparation of many important classes of organic compounds like natural and nonnatural a-amino acids, a-substituted nitriles and esters, cyanohydrins, 5-alkyl hydantoins, and thiazoUn-5-ones. 

The catalytic asymmetric hydrogenation with cationic Rh(I)-complexes is one of the best-understood selection processes, the reaction sequence having been elucidated by Halpern, Landis and colleagues [21a, b], as well as by Brown et al. [55]. Diastereomeric substrate complexes are formed in pre-equilibria from the solvent complex, as the active species, and the prochiral olefin. They react in a series of elementary steps - oxidative addition of hydrogen, insertion, and reductive elimination - to yield the enantiomeric products (cf. Scheme 10.2) [56]. 

The cis alkenes are more reactive and more selective than their trans counterparts. As with the Evans system, this reaction is not stereospecific. Acyclic cis alkenes provide mixtures of cis and trans aziridines. cis-p-Methylstyrene affords a 3 1 ratio of aziridines favoring the cis isomer, Eq. 67, although selectivity is higher in the trans isomer. A fascinating discussion of this phenomenon, observed in this system as well as the Mn-catalyzed asymmetric oxo-transfer reaction, has been advanced by Jacobsen and co-workers (83). Styrene provides the aziridine in moderate selectivity, Eq. 68, not altogether surprising since bond rotation in this case would lead to enantiomeric products. 

A corollary to the above argument is that enantioselectivities depend on alkene geometry. Indeed, isomeric enolsilanes provide enantiomeric products. Because obtaining enolsilanes such as 344 in high isomeric purity is difficult, enantioselectivities with these nucleophiles are reflective, Eqs. 214 and 215. Pyrrole-derived enolsilanes are accessible in very high isomeric purity (>99 1) thus providing a convenient solution to this problem. Their use in the catalytic amination reaction provides access to a-hydrazino acid derivatives in high enantioselectivity. 

Even less expected, perhaps, are the reactions involving gas-solid addition of HBr, Cl2, and Br2 to a, 3-unsaturated acid guest species in a- and P-cyclodextrin inclusion complexes (242). Although the chemical yields are not high, the optical yields in some cases are extraordinary. Thus, chlorine addition to methacrylic acid in a-cyclodextrin yields (- )-2,3-dichloro-2-methylpropanoic acid in nearly quantitative optical yield. The 3-cyclodextrin methacrylic acid clathrate undergoes chlorine addition to yield preferentially the enantiomeric (+ )-product, with an e.e. of 80%. 

The reaction occurs because a favourable tertiary carbocation is generated. Since the carbocation also has three different substituents, nucleophilic attack of water forms a chiral centre, and thus enantiomeric products. 

Quinine catalyzed reactions give enantiomeric products... 

Values in parentheses are for reactions using (DHQ)2AQN and give enantiomeric products... 

In this reaction, two diastereoisomeric pathways are possible the catalyst, because of the chiral diphosphine ligand, can coordinate to the enamide in two diastereoisomeric ways. As a result, the two substrate complexes exhibit different chemical reactivity. One of the complexes is quite stable and relatively unreactive while the other is highly reactive towards molecular hydrogen. The high reactivity of the latter leads to a high enantiomeric excess of the one enantiomeric product generated by this complex. The two diastereoisomers have been termed major and minor by Halpern [30] and the rule of thumb here is that minor gives major and vice versa. 

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