Chiral reactants

The addition of methylmagnesium iodide to 2-phenylpropanal is stereoselective in producing twice as much syn-3-phenyl-2-butanol as the anti isomer (entry 5). The stereoselective formation of a particular configuration at a new stereogenic center in a reaction of a chiral reactant is called asymmetric induction. This particular case is one in which the stereochemistry can be predicted on the basis of an empirical correlation called Cram s rule. The structural and mechanistic basis of Cramls rule will be discussed in Chapter 3. 

With an appropriate chiral reactant, high enantioselectivity can be achieved, as a result of asymmetric induction If both reactants are chiral, this procedure is called the double asymmetric reaction and the observed enantioselectivity can be even higher. 

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... 

As a general rule, the reaction of a chiral reactant with an achiral reactant leads to unequal amounts of diastereomeric products. If the chiral reactant is optically active because only one enantiomer is used rather than a racemic mixture, then the products are also optically active. 

Because an S jl reaction occurs through a carbocation intermediate, its stereochemical outcome is different from that of an S 2 reaction. Carbocations, as we ve seen, are planar, sp2-hybndized, and achiral. Thus, if we carry out an S jl reaction on one enantiomer of a chiral reactant and go through an achiral carbocation intermediate, the product must be optically inactive (Section 9.10). The symmetrical intermediate carbocation can react with a nucleophile equally well from either side, leading to a racemic, 50 50 mixture of enantiomers (Figure 11.10). 

These results reveal a high level of kinetic resolution between the respective chiral reactants. This is also indicated in the reaction between equimolar amounts of the anion of enantiomer-ically pure 3-[(/ M4-methylphenyl)sulfmyl]-l-propene and racemic 4-alkoxy-2-cyclopentenones. 

These reagents exhibit good stereoselectivity toward chiral reactants, such as acylox-azolidinones.253 Chiral oxaziridine reagents have been developed that can achieve enantioselective oxidation of enolates to a-hydroxyketones.254... 

Optically active product(s) requires chiral reactants, reagents, and/or solvents ... 

The first chapter in this volume is a particularly timely one given the recent surge of activity in natural product synthesis based upon stereocontrolled Aldol Condensations. D. A. Evans, one of the principal protagonists in this effort, and his associates, J. V. Nelson and T. R. Taber, have surveyed the several modem variants of the Aldol Condensation and discuss models to rationalize the experimental results, particularly with respect to stereochemistry, in a chapter entitled Stereoselective Aldol Condensations. The authors examine Aldol diastereoselection under thermodynamic and kinetic control as well as enantioselection in Aldol Condensations involving chiral reactants. 

A chemical reaction in which the reactant is converted into its mirror image, hence the name alluding to the self-admiring nature of the mythic Narcissus. In a narcissistic process, a chiral reactant can be converted into its enantiomer. Racemases catalyze the most obvious narcissistic biochemical reactions. Another example of a narcissistic reaction is degenerate rearrangement. 

Izumi and Tai29 discussed Horeau s results but used, for the same issue, the term double-differentiating reaction . With respect to terminology, there is an important difference between stereoselectivity and stereodifferentiation that will be outlined in the following section. Accordingly, there is a necessity for a definition double asymmetric induction is applied when a stereogenic unit(s) is (are) generated from two reactants that are both chiral or from one chiral reactant in the presence of a chiral additive. 

Reactions of the enolate derived from enantiomerically pure 5 with enantiomerically pure monosubstituted epoxides 3 are also shown in the table on p 952 it is noteworthy that very high selectivities are obtained regardless of the relative configurations of the two chiral reactants. 

Let us imagine a scenario where a chiral product of a given handedness has been formed by an absolute asymmetric synthesis. Episodic changes in temperature would induce melting of the system that comprises the chiral reactant product. Supplying additional substrate material and then reducing the temperature should result in additional crystallization of the reactant, but this... 

This possibility of intimate association of rhodium with the aromatic ring suggests further experiments. A logical extension of asymmetric syntheses involving prochir-al reactants is a kinetic resolution with related chiral reactants under similar conditions. In the one case of hydroboration-amination where this has been applied, it has proved to be very effective. The reactant was prepared directly by a Heck reaction on 1,2-dihydronaphthalene, and under the standard conditions of catalytic hydrobora-tion gave >45% of both enantiomerically pure recovered alkene with (after oxidative work-up) the alcohol of opposite hand, mainly as the trans-isomer. This procedure forms a simple and potentially useful route to pharmacologically active substances, demonstrated by the racemic synthesis shown [105] (Scheme 34). 

The purpose of this review is to examine the recent progress in the fi< of asymmetric photoreactions involving a chiral reactant, and to discuss the fact< that control the diastereodifferentiation. In the excited state as in the groi state, the level of asymmetric induction is strongly related to the conformation flexibility of the reactants. When carried out in the solid state, in a confin cavity of zeolites or in supramolecular scaffoldings, restrictions of the mobil occur, and photoreactions can become highly stereoselective. These aspects asymmetric induction will be covered in separate chapters, and this review v consider only diastereoselective photoreactions carried out in solution. ... 

Reaction of a chiral reactant with an achiral reactant leads to unequal amounts of diastereomeric products. 

Aldol additions between achiral reactants in chiral solvents have also been examined [157-159]. Only low asymmetric inductions ee = 2... 22%) have been found [158], A twofold stereodifferentiation is observed in aldol additions between chiral reactants carried out in chiral solvents [159]. However, asymmetric inductions caused by chiral solvents or cosolvents are usually rather small [157]. 

Asymmetric catalysis, the introduction of chirality into non-chiral reactants through usage of a chiral catalysts, is an important aspect of asymmetric synthesis. The most extensively studied asymmetric catalysis reaction is that of hydrogenation of alkenes. In... 

A number of fine studies have shown that high ee s can be achieved. It has generally proven feasible to determine the resultant chiral form from the chiral conformation of the reactant molecules in the crystal. Generally the optical product closest in geometry to the chiral reactant is the true final stereoisomer. Examples of this, 13 and 14, illustrate schematically the chiral conformation of the reactants and the chiral form of the products. Some recent studies include those in reference 36. 

When two of the reaction components are chiral (any combination of substrate, reagent, catalyst, or solvent), the chirality elements of each reactant will operate either in concert (matched pair) or in opposition (mismatched pair) and together influence the stereochemical outcome of the reaction. In this case, the reaction is subject to double asymmetric induction. Unless the diastereofadal selectivities of both chiral reactants are in opposition and identical in magnitude, the ratio C D 1. Applications of double asymmetric induction in synthesis will be discussed in Chapter 5. 

The stereochemical outcome of an aldol reaction involving more than one chiral component is consistent with the rule of approximate multiplicativity of diastereofacial selectivities intrinsic to the chiral reactants. For a matched case, the diastereoselectivity approximates (substrate DS) X (reagent DS). For a mismatched case, the diastereoselectivity is (substrate DS) (reagent DS). Double asymmetric induction also can be used to enforce the inherent facial selectivity of a chiral aldehyde, as shown below. 

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