First-Order Asymmetric Transformation

The literature contmns many references to widely different molecular systems in which a fixed and stable center of dissymmetry has apparently influenced in a one-sided manner an adjacent center of dissymmetry of a more labile but classical type. Kuhn (66) attempted to correlate systematically a number of these systems by introducing the conception of asymmetric transformation. He subdivided this into asymmetrische Um-l erung erster Art and asynunetrische Umlagerung zweiter Art. These 

Kuhn and Albrecht (67) noted that, when 4,4 -dinitrodiphenic acid is converted to its quinine (Q) salt, the latter is unexpectedly and strongly dextrorotatory they attributed this to the adoption by the biphenyl skeleton of a dissymmetric configuration induced by the optically active alkaloid, and persisting for only so long as the salt exists. This can only be inferred and not proved directly, for only an inactive acid can be liberated from the salt on acidification  

Similarly, Pfeiffer and Quehl (119) found that addition of a-phen-anthrolene to solutions of zinc camphorsulfonate causes a marked and unexpected diminution in the optical activity of the latter this has been attributed to the one-sided fohnation of [Zn(phen)8]+ ions (which possess a dissymmetric octahedral configuration) under the as3Tnmetric inductive influence of the sulfonate. Once again, however, direct and positive confirmation of this explanation is lacking, since only inactive fZn(phen)s]Br2 could be isolated on treatment with potassium bromide. 

Assuming for the moment the correctness of Kuhn s explanation of these and similar phenomena, we arrive at the conception of first-order asymmetric transformation— the activation of a configurationally labUe racemate in solution by addition of an optically stable (-1-) or (—) compound which combines with the racemate to form a pair of diastereoisomerides, in unequal amounts at equilibrium. In favorable cases, slow establishment of equilibrium might show itself by mutarotation. Lesslie and Turner (72) originally claimed to have observed this for solutions of quinine diphenate in chloroform, though later Lesslie, Turner, and Winton (73) re-examined and withdrew this claim. 

Jamison (51) points out that the essential condition for a first-order transformation is the reality of the diastereoisomerides in solution. If this is so, one would hardly expect the phenomenon to occur with diastereo-isomeric salts in ionizing solvents such as water or even, in the case of quaternary ammonium salts, in solvents such as chloroform. McKenzie and Wood (93) have concluded that the effect recorded by Kidin and Albrecht (67) may possibly have an alternative explanation. 

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A second method requires the formation of diastereomeric salts or covalent derivatives, which are in a mobile equilibrium in solution ( First-Order Asymmetric Transformation"). Again, one of the diastereomers crystallizes ( Second-Order Asymmetric Transformation ). 

Whenever x is greater than or less than 0.5, a rotation will be observed. Although the Pfeiffer and the Harris explanations appear to be identical, Harris contends, in opposition to Pfeiffer but in agreement with the present authors, that an A-B association of some kind is essential to the development of the Pfeiffer-type activity. The term first-order asymmetric transformation is used for a system in which no optically active phase other than that originally introduced can be isolated. If such a new phase is isolatable, the transition is called second order. Turner and Harris have used the former term (first order) to describe the observations of Pfeiffer, Dwyer, and others. ... 

Structurally similar acids, phthalic and m-benzoic exhibit levo rotation. Other studies show similar rotations when the cinchona alkaloids are used with various other diphenic acids. It has been suggested by Kuhn that a stereospecificity exists with these alkaloids in causing rotation of one phenyl group about the biphenyl bond leading to an unsymmetrical complex. Since no active phase (other than the original alkaloid) is isolable the system may be classified as a first order asymmetric transformation. 

It is obvious from the above that there is no clear-cut distinction between first-order asymmetric transformations, second-order asymmetric transformations, and the process of resolution by salt formation. An acid so optically stable that it does not undergo configurative inversion within the accessible range of experimental conditions will show straightforward resolution but an acid with a marked temperature coefficient of optical inversion might be made to show all three variations of the phenomenon under a ppropriate temperature conditions. 

Starting from a racemate, it is possible to prepare mixtures of enantionmers with a preponderance of one form in them. We have described this in asymmetric transformations, consequently we have first and second order asymmetric transformations. In a first order there is a shift of the equilibrium to the side of formation of one of the enantiomers in solution while in a second order there is a complete conversion of the racemate into one of the optically active forms. 

Quite a few complexes with the bidentate pentasulfido ligand are also known. The first reported was the homoleptic and optically active complex [Pt(85)3] (15) (53, 64, 65, 68, 69, 176). Brick-red (NH4)2[Pt(85)3] 2H20 is formed from the reaction of K2[PtCl6] with aqueous (NH4)28 solution. Addition of concentrated HCl results in the separation of maroon (NH4)2[Pt8i7] 2H20 (54). The [Pt(85)3] ion crystallizes from the solution as a racemate, which can be resolved by forming diastereoisomers. Upon crystallization, [Pt8,7] undergoes a second-order asymmetric transformation, so that the solid contains an excess of the (—) enantiomer (54). 

The first example of an asymmetric induction at tetragonal silicon was reported by Klebe and Finkbeiner42 and is shown in equation 3. The reaction of a prochiral bis-(acetamido)silane with optically active amino acids led to two diastereomeric 2-silaoxa-zolidones in unequal amounts. These diastereomers were shown to undergo a second-order asymmetric transformation crystallization was accompanied by a rearrangement of the less abundant into the more abundant diastereomer. From the silaoxazolidones, alcoholysis reactions yielded an optically active dialkoxysilane. 

Asymmetric transformation The conversion of a mixture (usually 1 1) of stereoisomers into a single stereoisomer or a mixture in which one isomer predominates. An asymmetric transformation of the first kind involves such a conversion without separation of the stereoisomers. An asymmetric transformation of the second kind also involves separation, such as an equilibration accompanied by selective crystallization of one stereoisomer [76]. The terms first- and second-order asymmetric transformations to describe these processes are inappropriate. See also stereoconvergent. 

Second order asymmetric transformation, in any case in which interconversion of diastereoisomerides is possible (first order transformation) and crystallisation can be induced, may be expected to be almost quantitatively realisable, and to give one dia-stereoisomeride in the optically pure crystalline condition. ... 

Here again, then, we see the artificial nature of Kuhn s original distinction between first- and second-order asymmetric transformations. A technic less refined than that employed in Smith s preparation of pure (+)-mandelonitrile (132) would exclude the possibility of proving directly the order of the transformation. 

Because in methanol crystallization of amino nitrile 3 did not take place, first the solvent was varied in order to attempt to find conditions for a crystallization-induced asymmetric transformation. At a MeOH/2-PrOH ratio of 1/9, the amino nitrile (R,S)-3 was isolated in 51% yield and dr 99/1 (entry 2). Other combinations of alcoholic solvents failed to lead to a higher yield of precipitated (R,S)-3 in high dr (entries 3 and 4). On further screening of solvents, it was observed that upon addition of HjO to the methanol solution selective precipitation of amino nitrile (R,S)-3 occurred giving (R,S)-3 and (R,R)-3 in a ratio of 81 19 and 69% yield (entry 5). The asymmetric Strecker reaction was further studied in HjO alone using temperature as a variable. The results of these experiments are given in Table 1 (entries 6-9). After addition of NaCN/AcOH at 23-28 °C... 

The configurationally most labile optically active square-pyramidal derivative shown to date is compound 25, simultaneously the first example of an optically active square-pyramidal complex having five independent ligands (67) (see Scheme 17). Starting with 25a in toluene solution at 0°C, the first-order approach to equilibrium proceeds with a half-life of 27 minutes. The extreme lability of the Mo configuration in 25a can be used for the following asymmetric transformation. If an equilibrium mixture of 25a and 25b that contains both isomers in the ratio —1 1 is cooled to -20°C, one isomer (25a) starts to crystallize. Because at -20°C, equilibration is still fairly rapid, 25b is steadily transformed into 25a until almost all the material is converted into solid 25a (67). No trace of the corresponding trans isomer can be seen in the H-NMR spectrum on equilibration. 

Figure 17 shows the results of this experiment with a-phenylbutyric acid replacing alanine. In this reaction, the asymmetric transformation is first order. 

The use of Lewis acids in order to catalyze hetero Diels-Alder reactions of thia-1,3-butadienes is not widespread, but recent investigations stemming from Saito et al. reveal a remarkable acceleration of these transformations in the presence of A1C13 or EtAlCl2 [428]. In a first study concerning asymmetric hetero Diels-Alder reactions of thia-1,3-butadienes, Saito et al. found Lewis acids to have a beneficial effect on the induced diastereoselectivities. Thus, the thioketone 5-17, generated in situ by thermal cycloreversion from its dimer, underwent a completely endo-selective cycloaddition upon treatment with (-)-dimenthyl... 

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