Enantiomer formation

JAHN-TELLER INDUCED SYMMETRY BREAKINGS IN STRUCTURAL PHASE TRANSITIONS, MELTING, VAPORIZATION, AND ENANTIOMER FORMATION... 

An interesting case of SB is presented by enantiomer formation. In recent papers [15] it was shown that enantiomers can be presented as the low symmetry, PJT distorted configurations of a hypothetical high-symmetry structure, and as such their interaction in the liquid phase via collisions under special conditions may lead to some kind of cooperativity and phase transition (SB) resulting in singleenantiomer broken symmetry configuration. 

Indeed, when 2-alkynylpyrimidine-5-carbaldehyde was reacted with z-Pr2Zn in a mixed solvent of ether and toluene, the subsequent one-pot asymmetric autocatalysis with amplification of ee gave enantiomerically enriched pyrimidyl alkanol 12 well above the detection level [103]. The absolute configurations of the pyrimidyl alkanol exhibit an approximate stochastic distribution of S and R enantiomers (formation of S 19 times and R 18 times) (Fig. 6). 

The trans-effect was also invoked to explain enantioselectivity in the Rh-catalyzed intermolecular hydroacylation (Figure 11.15). The preferred S-enantiomer formation is consistent with the productdetermining ketone insertion step where the ligand cooperatively renders the hydride more nucleophilic and the ketone more electrophilic. This synergy facilitates formation of the S-stereoisomer of the product in Figure 11.15. Conversely, the alternative complex is stabilized by the trans-effect, and the barrier to migratory insertion is increased as a consequence of this ground sate stabilization. 

Precautions should be taken to avoid racemization of the C-terminal amino add during the acylation reaction. Coupling with the carboxylate salt of the first amino acid to the halogenated linker is now popularly employed and many other methods have also been described to reduce enantiomer formation. 

Recently Desimoni et used the same bis(oxazoline) ligand in the magnesium(II) catalysed Diels-Alder reaction of the N-acyloxazolidinone depicted in Scheme 3.4. In dichloromethane a modest preference was observed for the formation of the S-enantiomer. Interestingly, upon addition of two equivalents of water, the R-enantiomer was obtained in excess. This remarkable observation was interpreted in terms of a change from tetrahedral to octahedral coordination upon the introduction of the strongly coordinating water molecules. 

Figure 7 7 shows why equal amounts of (R) and (5) 1 2 epoxypropane are formed m the epoxidation of propene There is no difference between the top face of the dou ble bond and the bottom face Peroxyacetic acid can transfer oxygen to either face with equal facility the rates of formation of the R and S enantiomers of the product are the same and the product is racemic... 

FIGURE 7 10 Stereo isomeric 2 3 butanediols shown in their eclipsed con formations for convenience Stereoisomers (a) and (b) are enantiomers of each other Structure (c) is a diastereo mer of (a) and (b) and is achiral It is called meso 2 3 butanediol... 

The reaction is used for the chain extension of aldoses in the synthesis of new or unusual sugars In this case the starting material l arabinose is an abundant natural product and possesses the correct configurations at its three chirality centers for elaboration to the relatively rare l enantiomers of glucose and mannose After cyanohydrin formation the cyano groups are converted to aldehyde functions by hydrogenation m aqueous solution Under these conditions —C=N is reduced to —CH=NH and hydrolyzes rapidly to —CH=0 Use of a poisoned palladium on barium sulfate catalyst prevents further reduction to the alditols... 

Most chiral chromatographic separations are accompHshed using chromatographic stationary phases that incorporate a chiral selector. The chiral separation mechanisms are generally thought to involve the formation of transient diastereomeric complexes between the enantiomers and the stationary phase chiral ligand. Differences in the stabiHties of these complexes account for the differences in the retention observed for the two enantiomers. Often, the use of a... 

The principle of this method depends on the formation of a reversible diastereomeric complex between amino acid enantiomers and chiral addends, by coordination to metal, hydrogen bonding, or ion—ion mutual action, in the presence of metal ion if necessary. L-Proline (60), T.-phenylalanine (61),... 

Kinetic Resolutions. From a practical standpoint the principal difference between formation of a chiral molecule by kinetic resolution of a racemate and formation by asymmetric synthesis is that in the former case the maximum theoretical yield of the chiral product is 50% based on a racemic starting material. In the latter case a maximum yield of 100% is possible. If the reactivity of two enantiomers is substantially different the reaction virtually stops at 50% conversion, and enantiomericaHy pure substrate and product may be obtained ia close to 50% yield. Convenientiy, the enantiomeric purity of the substrate and the product depends strongly on the degree of conversion so that even ia those instances where reactivity of enantiomers is not substantially different, a high purity material may be obtained by sacrificing the overall yield. 

Preparation of enantiomerically enriched materials by use of chiral catalysts is also based on differences in transition-state energies. While the reactant is part of a complex or intermediate containing a chiral catalyst, it is in a chiral environment. The intermediates and complexes containing each enantiomeric reactant and a homochiral catalyst are diastereomeric and differ in energy. This energy difference can then control selection between the stereoisomeric products of the reaction. If the reaction creates a new stereogenic center in the reactant molecule, there can be a preference for formation of one enantiomer over the other. 

It is a general principle that optically active products cannot be formed when optically inactive substrates react with optically inactive reagents. This principle holds itie-spective of whether the addition is syn or anti, concerted or stepwise. No matter how many steps are involved in a reaction, if the reactants ar e achiral, formation of one enantiomer is just as likely as the other, and a racemic mixture results. 

Among the J ,J -DBFOX/Ph-transition(II) metal complex catalysts examined in nitrone cydoadditions, the anhydrous J ,J -DBFOX/Ph complex catalyst prepared from Ni(C104)2 or Fe(C104)2 provided equally excellent results. For example, in the presence of 10 mol% of the anhydrous nickel(II) complex catalyst R,R-DBFOX/Ph-Ni(C104)2, which was prepared in-situ from J ,J -DBFOX/Ph ligand, NiBr2, and 2 equimolar amounts of AgC104 in dichloromethane, the reaction of 3-crotonoyl-2-oxazolidinone with N-benzylidenemethylamine N-oxide at room temperature produced the 3,4-trans-isoxazolidine (63% yield) in near perfect endo selectivity (endo/exo=99 l) and enantioselectivity in favor for the 3S,4J ,5S enantiomer (>99% ee for the endo isomer. Scheme 7.21). The copper(II) perchlorate complex showed no catalytic activity, however, whereas the ytterbium(III) triflate complex led to the formation of racemic cycloadducts. 

---