Reactions That Form Racemates

Enantiomeric Transition States Lead to Racemic Mixture 

---

The synthesis of a chiral amino acid from an achiral precursor by any of the methods described in the previous section yields a racemic mi.xture— an equal mixture of S and R products. To use these synthetic amino acids for the laboratory synthesis of naturally occurring proteins, however, the racemic mixture must first be resolved into pure enantiomers. Sometimes this resolution can he done by allowing the racemic amino acid to undergo a reaction that forms two diastereomers, which are then separated and converted back to the amino acid (Section 9.10). 

When a reactant that does not have an asymmetric carbon undergoes a reaction that forms a product with one asymmetric carbon, the product will be a racemic mixture. For example, the reaction of 1-butene with HBr forms identical amounts of (/ )-2-bromobutane and (5)-2-bromobutane. Thus, an electrophilic addition reaction that forms a compound with one asymmetric carbon from a reactant without any asymmetric carbons is not stereoselective because it does not select for a particular stereoisomer. Why is this so ... 

A racemic mixture is formed by any reaction that forms a product with an asymmetric center from a reactant that does not have an asymmetric center. The products of the following reactions, therefore, are racemic mixtures. 

If the reaction with the carbonyl compound forms a product with an asymmetric center, such as the preceding reaction that forms 1-phenyl-1-butanol, the product will be a racemic mixture. (Recall that when a reactant without an asymmetric center undergoes a reaction that forms an asymmetric center, then the product will be a racemic mixture Section 6.15.)... 

Carbamates can be used as protective groups for amino acids to minimize racem-ization in peptide synthesis. Racemization occurs during the base-catalyzed coupling reaction of an A-protected, carboxyl-activated amino acid and takes place in the intermediate oxazolone that forms readily from an A-acyl-protected amino acid (R = alkyl, aryl) ... 

Most of the biochemical reactions that take place in the body, as well as many organic reactions in the laboratory, yield products with chirality centers. Fo example, acid-catalyzed addition of H2O to 1-butene in the laboratory yield 2-butanol, a chiral alcohol. What is the stereochemistry of this chiral product If a single enantiomer is formed, is it R or 5 If a mixture of enantiomers i formed, how much of each In fact, the 2-butanol produced is a racemic mix ture of R and S enantiomers. Let s see why. 

Scheme 8 presents the sequence of reactions that led to the synthesis of the B-ring of vitamin B12 by the Eschenmoser group. An important virtue of the Diels-Alder reaction is that it is a stereospecific process wherein relative stereochemical relationships present in the diene and/or the dienophile are preserved throughout the course of the reaction.8 Thus, when the doubly activated dienophile 12 (Scheme 8) is exposed to butadiene 11 in the presence of stannic chloride, a stereospecific reaction takes place to give compound 27 in racemic form. As expected, the trans relationship between... 

Having retraced the efficient and elegant sequences of reactions that have led to the synthesi of key intermediates 11 and 12, we are now in a position to address their union and the completion of the total synthesis of erythronolide B. Taken together, intermediates 11 and 12 contain all of the carbon atoms of erythronolide B, and although both are available in optically active form of the required absolute configuration, racemic 11 and enantiomerically pure 12... 

Even if the organometallic compound is racemic, it still may be possible to get a diastereoselective reaction that is, one pair of enantiomers is formed in greater amount than the other. 

Racemization a reaction that transforms an optically active compound into a racemic form. 

The relative ease with which aryl benzyl sulfoxides undergo homolytic dissociation (Rayner et al., 1966) as compared to aryl benzyl sulfides or sulfones is supportive of this idea that ArSO radicals are easier to form than ArS or ArS02 radicals. Another interesting set of observations is the following. Booms and Cram (1972) found that optically active arene-sulfinamides ArS(0)NRPh (R = H or CH3) racemize thermally very readily at room temperature and that this racemization is the result of a free radical chain reaction (160) that is initiated by the dissociation of some of the sulfinamide into an ArSO and a PhNR radical (159). While the length of the inhibition... 

With 6 -hydroxychalcones, such as naringenin chalcone, the isomerization reaction can readily occur nonenzymically to form racemic (2R,2S) flavanone. This occurs easily in vitro and has been reported to occur in vivo to the extent that moderate levels of anthocyanin can be formed. However, 6 -deoxychalcones are stable under physiological conditions, due to an... 

In a number of nonenzymatic reactions catalyzed by pyridoxal, a metal ion complex is formed—a combination of a multivalent metal ion such as cupric oi aluminum ion with the Schiff base formed from the combination of an amino acid and pyridoxal (I). The electrostatic effect of the metal ion, as well as the electron sink of the pyridinium ion, facilitates the removal of an a -hydrogen atom to form the tautomeric Schiff base, II. Schiff base II is capable of a number of reactions characteristic of pyridoxal systems. Since the former asymmetric center of the amino acid has lost its asymmetry, donation of a proton to that center followed by hydrolytic cleavage of the system will result in racemic amino acid. On the other hand, donation of a proton to the benzylic carbon atom followed by hydrolytic cleavage of the system will result in a transamination reaction—that is, the amino acid will be converted to a keto acid and pyridoxal will be converted to pyridoxamine. Decarboxylation of the original amino acid can occur instead of the initial loss of a proton. In either case, a pair of electrons must be absorbed by the pyridoxal system, and in each case, the electrostatic effect of the metal ion facilitates this electron movement, as well as the subsequent hydrolytic cleavage (40, 43). 

---