Racemates production

Formation of a racemic product by nucleophilic substitution via a carbocation... 

Stereochemical analysis can add detail to the mechanistic picture of the Sj l substitution reaction. The ionization mechanism results in foimation of a caibocation intermediate which is planar because of its hybridization. If the caibocation is sufficiently long-lived under the reaction conditions to diffirse away from the leaving group, it becomes symmetrically solvated and gives racemic product. If this condition is not met, the solvation is dissymmetric, and product with net retention or inversion of configuration may be obtained, even though an achiral caibocation is formed. The extent of inversion or retention depends upon the details of the system. Examples of this effect will be discussed in later sections of the chapter. 

This intermediate serves to explain the formation of racemic product, since it is achiral. The cation has a plane of symmetry passing through C-4, C-5, C-6, and the midpoint of... 

The description of the nonclassical norbomyl cation developed by Wnstein implies that the nonclassical ion is stabilized, relative to a secondary ion, by C—C a bond delocalization. H. C. Brown of Purdue University put forward an alternative interpreta-tioiL He argued that all the available data were consistent with describing the intermediate as a rapidly equilibrating classical ion. The 1,2-shift that interconverts the two ions was presumed to be rapid relative to capture of the nucleophile. Such a rapid rearrangement would account for the isolation of racemic product, and Brown proposed that die rapid migration would lead to preferential approach of the nucleophile fiom the exo direction. 

Next, examine each cation s LUMO while displaying the cation as a space-filling model. Assuming that Br preferentially attacks the side of that is both less hindered and permits better overlap with the LUMO, predict the major product obtained from each cation conformer (if the two sides of C+ seem equally reactive, then predict a racemic product mixture). 

Hie necessity of an anionic tbiolale ligand was established by perforniing reactions with ferrocene tliioetliets 37 as ligands. Here, essentially racemic products... 

With this epoxidation procedure it is possible to convert the achiral starting material—i.e. the allylic alcohol—with the aim of a chiral reagent, into a chiral, non-racemic product in many cases an enantiomerically highly-enriched product is obtained. The desired enantiomer of the product epoxy alcohol can be obtained by using either the (-1-)- or (-)- enantiomer of diethyl tartrate as chiral auxiliary ... 

To understand why a racemic product results from the reaction of T120 wjtl 1-butene, think about the reaction mechanism. 1-Butene is first protonaled tc yield an intermediate secondary (2°) carbocation. Since the trivalent carbon i sp2-hybridized and planar, the cation has no chirality centers, has a plane o symmetry, and is achiral. As a result, it can react with H20 equally well fron either the top or the bottom. Reaction from the top leads to (S)-2-butano through transition state 1 (TS 1) in Figure 9.15, and reaction from the bottorr leads to R product through TS 2. The two transition states are mirror images. The] therefore have identical energies, form at identical rates, and are equally likeb to occur. 

Figure 11.10 Stereochemistry of the S j1 reaction. Because the reaction goes through an achiral intermediate, an enantiomeri-cally pure reactant should give a racemic product.

The conclusion that SN1 reactions on enantiomerically pure substrates should give racemic products is nearly, but not exactly, what is found. In fact, few S jl displacements occur with complete racemization. Most give a minor (0%-20%) excess of inversion. The reaction of (J )-6-cbloro 2,6 dimethyloctane with I420, for example, leads to an alcohol product that is approximately 80% racemized and 20% inverted (80% R,S + 20% S is equivalent to 40% R + 60% S). 

Would you expect the Friedel-Crafts reaction of benzene with (P)-2-chloro-butane to yield optically active or racemic product Explain. 

The evidence presented so far excludes the formation of dissociated ions as the principal precursor to sulfone, since such a mechanism would yield a mixture of two isomeric sulfones. Similarly, in the case of optically active ester a racemic product should be formed. The observed data are consistent with either an ion-pair mechanism or a more concerted cyclic intramolecular mechanism involving little change between the polarity of the ground state and transition state. Support for the second alternative was found from measurements of the substituent and solvent effects on the rate of reaction. 

One type of evidence for an SET mechanism is the finding of some racemization. A totally free radical would of course result in a completely racemized product RY, but it has been suggested that inversion can also take place in some SET processes. The suggestion is that in step 1 the Y still approaches from the backside, even though an ordinary Sn2 mechanism will not follow, and that the radical R-, once formed, remains in a solvent cage with Y- still opposite X , so that steps 1, 2, and 3 can lead to inversion. 

Many chemical reactions and processes yield cationic racemic products, and either a resolution or a stereoselective synthesis must be envisaged to obtain the chiral cations in an enantioenriched or enantiopure form. Resolution has been strongly studied [130] and selected representative examples of such processes mediated by chiral P( VI) anions are presented. 

Some solid-solid reactions were shown to proceed efficiently in a water suspension medium in Sect. 2.1. When this reaction, which gives a racemic product, is combined with an enantioselective inclusion complexation with a chiral host in a water suspension medium, a unique one-pot preparative method of optically active product in a water medium can be constructed. Some such successful examples are described. 

Hydrogenation of the free acids over unmodified catalyst occurred slowly, proceeded to completion in 20 h and gave racemic product as expected Enantioselective hydrogenation occurred at a slower rate over alkaloid-modified catalyst, cinchonidine modification providing an excess of S-product and cinchonine an excess ofR-product... 

The hydrogenation of methyl pyruvate proceeded over 4% Pd/Fe20 at 293 K and 10 bar when the catalyst was prepared by reduction at room temperature Racemic product was obtained over utunodified catalyst, modification of the catalyst with a cinchona alkaloid reduced reaction rate and rendered the reaction enantioselective. S-lactate was formed in excess when the modifier was cinchonidine, and R-lactate when the modifier was cinchonine... 

The carbon-carbon double bond that undergoes hydrogenation is remote from the modifier and no rate enhancement for the enantioselective process is to be expected. None was observed. Moreover, since the rate at the enantioselective sites is the same as that at other sites on the surface that experience no chiral environment and so give racemic product, the overall enantiomeric excess should be modest, as is the case To obtain higher... 

The hydrogenation of ehtyl pyurvate (EtPy) was carried out at 23 °C in a SS autoclave equipped with an injection chamber for separate introduction of the modifier Cinchonidine (CD) and Troger s base (TB) was used as modifiers. Different batches of EtPy, (Fluka) and Pt/Al203 catalysts (Engelhard E 4759, 5 %w Pt, Dpt = 25 %) were used. Experimental details incliding GC analysis can be found elsewhere [3,12]. The optical yield was calculated as e.e. = ([R]-[S])/([R]+[S]). The e.e. values were corrected for the amount of racemic product formed in minor amount in the reactor prior to the injection of CD. 

Bode and co-workers have extended the synthetic ntility of homoenolates to the formation of enantiomerically enriched IV-protected y-butyrolactams 169 from saccharin-derived cyclic sulfonylimines 167. While racemic products have been prepared from a range of P-alkyl and P-aryl substitnted enals and substitnted imi-nes, only a single example of an asymmetric variant has been shown, affording the lactam prodnct 169 with good levels of enantioselectivity and diastereoselectivity (Scheme 12.36) [71], As noted in the racemic series (see Section 12.2.2), two mechanisms have been proposed for this type of transformation, either by addition of a homoenolate to the imine or via an ene-type mechanism. 

The Al-Me complexes 28a-b were catalyst precursors for the reaction, which was not affected by air or water and did not require dry or degassed reagents. This system gave high yields but ees ranged only from 10 to 54% with 28a. In contrast, the t-Bu-substituted SALEN complex 28b gave racemic products at a slower rate [32]. 

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