Asymmetric induction principle

Enantioselective electron transfer reactions are not possible in principle because the electron cannot possess chirality. Whenever the choice of enantiodifferentiation becomes apparent, it will occur in chemical steps subsequent (or prior) to electron transfer. Thus, enantioselectivities require a chiral environment in the reaction layer of electrochemical intermediates although asymmetric induction was report-... 

Although this general principle of asymmetric induction has not been demonstrated for boron enolates, the related addition reactions of allylboranes to aldehydes (eq. [115]) (131) have been examined in this context. The reaction of chiral diol 175 with either triallyl-borane or tri- -methallylborane afforded the boronic esters 176 (Ri = H, Me) in yields exceeding 95% (132a). The addition reactions of 176 to representative aldehydes are summarized in Table 40. In all cases reported, the sense of asymmetric induction from the chiral... 

According to this correlation model, in which the principles of steric control of asymmetric induction at carbon (40) are applied, the stereoselectivity of oxidation should depend on the balance between one transition state [Scheme 1(a)] and a more hindered transition state [Scheme 1(6)] in which the groups and R at sulfur face the moderately and least hindered regions of the peroxy acid, respectively. Based on this model and on the known absolute configuration of (+)-percamphoric acid and (+)-l-phenylperpropionic acid, the correct chirality at sulfur (+)-/ and (-)-5 was predicted for alkyl aryl sulfoxides, provided asymmetric oxidation is performed in chloroform or carbon tetrachloride solution. Although the correlation model for asymmetric oxidation of sulfides to sulfoxides is oversimplified and has been questioned by Mislow (41), it may be used in a tentative way for predicting the chirality at sulfur in simple sulfoxides. 

If stoichiometric quantities of the chiral auxiliary are used (i.e., if the chiral auxiliary is covalently bonded to the molecule bearing the prochiral centres) there are in principle three possible ways of achieving stereoselection in an aldol adduct i) condensation of a chiral aldehyde with an achiral enolate ii) condensation of an achiral aldehyde with a chiral enolate, and iii) condensation of two chiral components. Whereas Evans [14] adopted the second solution, Masamune studied the "double asymmetric induction" approach [22aj. In this context, the relevant work of Heathcock on "relative stereoselective induction" and the "Cram s rule problem" must be also considered [23]. The use of catalytic amounts of an external chiral auxiliary in order to create a local chiral environment, will not be considered here. 

In principle, the approach outlined above for the a-oxoamides can be applied to any reaction, ground or excited state, which converts an achiral reactant into a chiral product, and Toda, Tanaka, and coworkers have investigated a wide variety of such processes [ 15,16]. A complete discussion of their work is beyond the scope of this review, and we illustrate the general approach taken with one final example. As shown in Scheme 4, irradiation of crystalline complexes of ene-diones 20a-f with chiral host (R,R)-(-)-9b led to cyclized products 21a-f in the variable yields and ee values indicated in Table 1 [22]. Remarkably, for reasons that were not clear (there was no accompanying X-ray crystallography), the R=n-propyl derivative 20g was found to give a completely different photoproduct, spiro compound 22 (69% yield, 97% ee, stereochemistry unknown), a result that once again illustrates the rather capricious nature of the use of chiral hosts for asymmetric induction. 

The process by which a stereochemically inactive center is converted to a specific stereoisomeric form. In most cases, the reacting center is prochiral. Such processes can occur with reactions involving an optically active reagent, solvent, or catalyst (eg., an enzyme). The reaction produced by such a process is referred to as an enantioselective reaction. In principle, use of circularly polarized light in photochemical reactions of achiral reactants might also exhibit asymmetric induction. However, reported enantioselectivities in these cases have been very small. 

If it is assumed that the Curtin-Hammett principle applies, one need only to compare the energies of the minima on the solid and dashed curves to be able to predict the structure of the major product. These curves also allow a direct comparison of Cram s, Cornforth s, Karabatsos s and Felkin s model for 1,2 asymmetric induction. Both Figures show the Felkin transition states lying close to the minima. The Corn-forth transition states (Fig. 3) are more than 4 kcal/mol higher and should contribute little to the formation of the final products assuming a Boltzmann distribution for the transition states, less than one molecule, out of a thousand, goes through them. Similarly, Fig. 4 shows the Cram and Karabatsos transition states to lie more than 2.7 kcal/mol above the Felkin transition states, which means that they account for less than 1% of the total yield. 

Optically active aldehydes are available in abundance from amino and hydroxy acids or from carbohydrates, thereby providing a great variety of optically active nitrile oxides via the corresponding oximes. Unfortunately, sufficient 1,4- or 1,3-asymmetric induction in cycloaddition to 1-alkenes or 1,2-disubstituted alkenes has still not been achieved. This represents an interesting problem that will surely be tackled in the years to come. On the other hand, cycloadditions with achiral olefins lead to 1 1 mixtures of diastereoisomers, that on separation furnish pure enantiomers with two or more stereocenters. This process is, of course, related to the separation of racemic mixtures, also leading to both enantiomers with 50% maximum yield for each. There has been a number of applications of this principle in synthesis. Chiral nitrile oxides are stereochemicaUy neutral, and consequently 1,2-induction from achiral alkenes can fully be exploited (see Table 6.10). 

There is an important difference between Horeau s and Heathcock s examples in that the aldol reaction generates two chirality elements in the bond-forming step. In principle, analysis of such a reaction requires evaluation of two aspects, i.e., the effect of double asymmetric induction on simple and induced diastereoselectivity. The aldol reaction is not particularly suited for this... 

Substrate-induced diastereoselection is the most common principle in alkylations of enolates derived from ketones. There are numerous successful applications reported in the literature (for extensive reviews, see refs 1, 3, and 79). The following account does not cover this extensive field with all its applications in detail, but rather presents representative examples which provide a general overview of the different synthetic methods available for alkylations of ketone enolates of various structural types, as well as demonstrating that remote asymmetric induction can be efficient and predictable. 

Optimum enantiomeric excesses are obtained when a bulky substituent R1 sterically shields the top face of the 4,5-dihydrooxazole. The introduction of the methoxymethyl side chain, serving as an additional ligand of the azaenolate counterion to generate a rigid chelate, was essential for achieving maximum asymmetric induction. This principle, initially demonstrated in the asymmetric alkylation of 4,5-dihydrooxazoles, has found further application in the asymmetric alkylation... 

Principles. How shall we proceed toward catalytic asymmetric induction Scheme 5 illustrates a possible way to achieve enantioselective alkylation by using a small amount of chiral source. Under certain conditions, the presence of a protic chiral auxiliary HX can catalyze the addition of organometallic reagent, R2M, to a prochiral carbonyl substrate by way of RMX. To obtain sufficient chiral efficiency, the anionic ligand X must have a three-dimensional structure that allows differentiation between the diastereomeric transition states of the alkyl transfer step. In addition, unlike in stoichiometric reactions, the rate of... 

The mechanism of the asymmetric induction in asymmetric catalysis by transition metal complexes is only speculation. In principle, the asymmetric induction can result from direct interaction between ligand and substrate as proposed, for instance, by McQuillin et al. (32) for the asymmetric hydrogenation. But it might take place simply by interaction between substrate and chiral transition metal atoms without... 

In principle, an asymmetric polymerization might be obtained either by asymmetric induction brought about by an asymmetric terminal group initiating the stereospecific chain growth, or by the steric control, done by the asymmetric catalyst, of the electrophilic or nucleophilic attack of the growing chain on the monomer, or by both factors. 

The synthesis of optically active polymers from racemic monomers could in principle be ascribed i) to asymmetric induction by optically active terminal groups of the macromolecules originally present in the catalyst, ii) to a steric control of the propagation exerted by the intrinsically asymmetric active centers of the catalyst, or iii) to both these factors. 

Fig. 1. Underlying Principle of the Asymmetric Induction, schematically (cf. text)...

Asymmetric synthesis via enolate intermediates has been extensively studied. Asymmetric induction can be divided into five main categories (1) a chiral auxiliary covalently linked to an enolate moiety,2,3 (2) a chiral ligand of a countercation of an enolate,4-6 (3) a chiral electrophile,7,8 (4) a chiral Lewis acid,9,10 and (5) a chiral phase-transfer catalyst.11,12 Rather than reviewing these examples, we introduce here the principle of asymmetric induction for... 

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