Pathway achiral

The asymmetric tetrahedron with unlabeled vertices is the three-dimensional analog of the unlabeled scalene triangle. While conversion of such a tetrahedron to its enantiomorph by way of an achiral tetrahedron is certainly not excluded, as illustrated in Fig. 2 for interconversion by way of a Cj-symmetric intermediate, achiral pathways are easily circumvented because the set of achiral unlabeled tetrahedra in E, unlike the set of achiral unlabeled triangles in E, does not form a boundary between heterochiral sets. 

FIGURE 2 Conversion of an unlabeled asymmetric tetrahedron (left) into its mirror image (right) by continuous deformation (small arrows) of the geometric figure along an achiral pathway. The achiral intermediate (center) has C, symmetry. 

The existence of chiral pathways in this molecule is made possible by the existence of the two independent degrees of freedom that govern internal motion, rotation, and inversion. As molecular complexity increases, the number of degrees of freedom also increases and, unless an achiral pathway is energetically much preferred, it becomes more and more likely that enantiomerization proceeds by a chiral pathway. For example, it is extremely improbable that reversal of helicity in a polymeric chain involves an achiral intermediate or transition state. There is a strong resemblance here to the stochastic achirality of ensembles of achiral molecules discussed previously. 

A formal limit is reached when, due to structural constraints, all achiral pathways along the enantiomerization trajectory become energetically inaccessible under normal laboratory conditions. Chiral pathways then remain the only alternative. In 1954 it was pointed out that a compound of the type 4-[( )-5ec-butyl]-4 -[(S)- ec-butyl]-2,2, 6,6 -tetra-methylbiphenyl consists entirely of asymmetric molecules that undergo rapid enantiomerization, and that conformational racemization, in the... 

Because enantiomers have oppositely signed pseudoscalar properties, chiral zeroes are unavoidable at some stage in the conversion of a molecule into its enantiomer along a chiral pathway. This is true of chirally connected enantiomeric conformations in chemically achiral molecules, such as (lf )-menthyl (15)-menthyl 2,2, 6,6 -tetranitro-4,4 -diphenate, and of chirally connected enantiomers, such as ( + )- and (- )-isopro-pylmalonamic acids. More generally, as previously noted, any chiral molecule composed of five or more atoms is in principle always capable of conversion into its enantiomer by chiral as well as by achiral pathways, provided that this is energetically feasible. Hence, unless it can be demon-... 

Divalent sulfur compounds are achiral, but trivalent sulfur compounds called sulfonium stilts (R3S+) can be chiral. Like phosphines, sulfonium salts undergo relatively slow inversion, so chiral sulfonium salts are configurationally stable and can be isolated. The best known example is the coenzyme 5-adenosylmethionine, the so-called biological methyl donor, which is involved in many metabolic pathways as a source of CH3 groups. (The S" in the name S-adenosylmethionine stands for sulfur and means that the adeno-syl group is attached to the sulfur atom of methionine.) The molecule has S stereochemistry at sulfur ana is configurationally stable for several days at room temperature. Jts R enantiomer is also known but has no biological activity. 

With the demonstration of the pathways described above it became abundantly clear that the formation of endiandric acids in nature from polyunsaturated achiral precursors is quite feasible without the participation of enzymes, as Black had so insightfully suggested in 1980. 

The rearrangement of allylic sulfoxides to allylic sulfenates was first studied in connection with the mechanism of racemization of allyl aryl sulfoxides.272 Although the allyl sulfoxide structure is strongly favored at equilibrium, rearrangement through the achiral allyl sulfenate provides a low-energy pathway for racemization. 

Sn(OTf)2 can function as a catalyst for aldol reactions, allylations, and cyanations asymmetric versions of these reactions have also been reported. Diastereoselective and enantioselective aldol reactions of aldehydes with silyl enol ethers using Sn(OTf)2 and a chiral amine have been reported (Scheme SO) 338 33 5 A proposed active complex is shown in the scheme. Catalytic asymmetric aldol reactions using Sn(OTf)2, a chiral diamine, and tin(II) oxide have been developed.340 Tin(II) oxide is assumed to prevent achiral reaction pathway by weakening the Lewis acidity of Me3SiOTf, which is formed during the reaction. 

Since our first model system is achiral, we did not need to consider different diastereomeric manifolds. However, we did need to follow four different reaction pathways corresponding to the four possible cis -dihydride isomers (Figure 5). Intermediates with traits phosphorus orientations were not considered because the catalysts of interest have chelating diphosphine ligands. 

F i g u re 18.1 One pathway of arachidonic acid metabolism. The branches of this pathway lead to the prostaglandins (PGs), prostacyclins (PGIs), and thromboxanes (TxBs). The key reaction is the formation of PGH2, creating five chiral centers from an achiral molecule. (Modified from D. Voet and J. G. Voet, Biochemistry, 3rd edn, 2004. Reprinted with permission John Wiley and Sons Inc.)... 

Finally, achiral phosphonium salts have been applied as Lewis acid catalysts in some other reactions. The examples will be listed here but not discussed in more detail. Phosphonium salts have been used as catalysts for the A,A-dimethylation of primary aromatic amines with methyl alkyl carbonates giving the products in good yields [123]. In addition acetonyltriphenylphosphonium bromide has been found to be a catalyst for the cyclotrimerization of aldehydes [124] and for the protection/ deprotection of alcohols with alkyl vinyl ethers [125, 126]. Since the pK of the salt is 6.6 [127-130], the authors proposed that, next to the activation of the phosphonium center, a Brpnsted acid catalyzed pathway is possible. 

In principle, the mechanism of homogeneous hydrogenation, in the chiral as well as in the achiral case, can follow two pathways (Figure 9.5). These involve either dihydrogen addition, followed by olefin association ( hydride route , as described in detail for Wilkinson s catalyst, vide supra) or initial association of the olefin to the rhodium center, which is then followed by dihydrogen addition ( unsaturate route ). As a rule of thumb, the hydride route is typical for neutral, Wilkinson-type catalysts whereas the catalytic mechanism for cationic complexes containing diphosphine chelate ligands seems to be dominated by the unsaturate route [1]. 

The group of Roelens published an organic pathway to substituted p-lactones from achiral p-carbonylesters via asymmetric hydrogenation using (/ )-BINAP-Ru (II) as catalyst yielding p-lactones with an ee of 97% [110] (Fig. 38). 

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