Racemization complete

The few studies that have been carried out with optically active tertiary alcohols indicate that almost complete racemization accompanies the preparation of tertiary alkyl halides by this method... 

AC2O, FeCl3, 80°, 24 h. In this case the methyl ether is converted to an acetate. The reaction proceeds with complete racemization. 

The acetolyses of both ero-2-norbomyl brosylate and e do-2-norbomyl brosylate produce exclusively exo-2-norbomyl acetate. The exo-brosylate is more reactive than the endo isomer by a factor of 350. Furthermore, enantiomerically enriched exo-brosylate gave completely racemic ero-acetate, and the endo-brosylate gave acetate that was at least 93% racemic. 

If, however, the /7-nitrophenyl ester of iV-henzoyl-L-leucine is treated with 1-methyl-piperidine in chloroform for 30 min and then coupled with glycine ethyl ester, the dipeptide isolated is almost completely racemic. Furthermore, treatment of the p-nitrophenyl ester of iV-benzoyl-L-leucine with 1-methylpiperidine alone leads to the formation of a crystalline material, C13H15NO2, having strong IR bands at 1832 and 1664 cm . Explain these observations, and suggest a reasonable stmcture for the crystalline 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). 

This lack of complete racemization in most SKd reactions is due to the fact that ioti pairs are involved. According to this explanation, first proposed by Saul Winstein, dissociation of the substrate occurs to give a structure in which the two ions are still loosely associated and in which the carbocation is effectively shielded from reaction on one side by the departing anion. If a certain amount of substitution occurs before the two ions fully diffuse apart, then a net inversion of configuration will be observed Figure 11.11). 

Figure 11.11 Ion pairs in an S l reaction. The leaving group shields one side of the carbocation intermediate from reaction with the nucleophile, thereby leading to some inversion ol configuration rather than complete racemization.

Like the kinetic evidence, the stereochemical evidence for the SnI mechanism is less clear-cut than it is for the Sn2 mechanism. If there is a free carbocation, it is planar (p. 224), and the nucleophile should attack with equal facility from either side of the plane, resulting in complete racemization. Although many first-order substitutions do give complete racemization, many others do not. Typically there is 5-20% inversion, though in a few cases, a small amount of retention of configuration has been found. These and other results have led to the conclusion that in many SnI reactions at least some of the products are not formed from free carbocations but rather from ion pairs. According to this concept," SnI reactions proceed in this manner ... 

In this scheme, RS and SR represent enantiomers, and so on, and 5 represents some fraction. The following are the possibilities (1) Direct attack by SH on RX gives SR (complete inversion) in a straight Sn2 process. (2) If the intimate ion pair R X is formed, the solvent can attack at this stage. This can lead to total inversion if Reaction A does not take place or to a combination of inversion and racemization if there is competition between A and B. (3) If the solvent-separated ion pair is formed, SH can attack here. The stereochemistry is not maintained as tightly and more racemization (perhaps total) is expected. (4) Finally, if free R" " is formed, it is planar, and attack by SH gives complete racemization. 

The ion-pair concept thus predicts that SmI reactions can display either complete racemization or partial inversion. The fact that this behavior is generally found is evidence that ion pairs are involved in many SnI reactions. There is much other evidence for the intervention of ion pairs ... 

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. 

According to the literature, desulfurization of thioic acids with Ra-Ni proceeds with retention of configuration 402 403 But use of the literature method invariably gave partially or completely racemized products.404 Finally, ultrasonic irradiation of a degassed mixture of the starting compound and Ra-Ni in... 

Erickson and Fischer have not been able to reproduce this result, however 23f They found that the products isolated from reduction of either 13 or its ethyl ester (14) are essentially completely racemic, thus making the stereochemistry of electrochemical reduction of 13 consistent with that of 11. 

Few SnI displacements occur with complete racemization. Most give a minor... 

Stannane 37 lost 50% of its optical activity when allowed to stand as a 0.2 M solution in benzene for 17 days. Addition of A1BN to the solution at 80 °C caused complete racem-ization after 30 min. With added hydroquinone, the benzene solution at 80 °C showed no decrease in rotation after 2 h. It was thus concluded that racemization proceeds by homolysis. 

Studies aimed at the elucidation of reaction mechanisms have been performed by many groups, notably by those of Backvall [28]. In test reactions, typically enantiopure 1-phenylethanol labeled with deuterium at the 1-position (8) is used. The compound is racemized with acetophenone (9) under the influence of the catalyst and after complete racemization of the alcohol, the deuterium content of the racemic alcohol is determined. If deuterium transfer proceeds from the a-carbon atom of the donor to the carbonyl carbon atom of the acceptor the deuterium is retained, but if it is transferred to the oxygen atom of the acceptor it is lost due to subsequent exchange with alcohols in the reaction mixture (Scheme 20.4). 

DPIBF, which does not apply at 53 °C. These findings are in line with a calculated barrier to enantiomerization of 15-18 kcalmol-1 (see Scheme 6.3). In their second investigation, Balci and Jones [46] eliminated hydrogen bromide from 32b at 53 °C with a pure enantiomer of potassium menthoxide in the presence of DPIBF, which gave rise to optically active products 50. Again, racemic products were formed on repetition of the experiment at 100 °C. Here, the base causes an enantioselective elimination from 32b with formation of non-racemic 6, which is trapped at 53 °C before complete racemization occurs. 

The retention of optical activity of camphene rules out methyl migration (Nametkin rearrangement) (71) or a symmetrical intermediate. On the acidic alumina at low contact time the retention of optical activity is high, about 80%. At longer contact time, however, there is essentially complete racemization. Hence, the dehydration mechanism seems to be the same on the acidic and on the base-modified alumina. The acidic alumina, however, causes the readsorption of the dehydration product leading to isomerization and equilibration. 

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