Mechanisms racemization

The racemization mechanism of sec-alcohols has been widely studied [16,17]. Metal complexes of the main groups of the periodic table react through a direct transfer of hydrogen (concerted process), such as aluminum complexes in Meerwein-Ponn-dorf-Verley-Oppenauer reaction. However, racemization catalyzed by transition metal complexes occurs via hydrogen transfer processes through metal hydrides or metal dihydrides intermediates (Figure 4.5) [18]. 

To confirm this racemization mechanism, Crawford et al. added 5 mol % of the ketone to the reaction mixture and obtained the product in 78% yield in >98% ee. This DKR is therefore catalyzed by a carbonyl compound, and can be compared to those shown in Section 4.6. 

On the other hand, optically active telluroxides have not been isolated until recently, although it has been surmised that they are key intermediates in asymmetric synthesis.3,4 In 1997, optically active telluroxides 3, stabilized by bulky substituents toward racemization, were isolated for the first time by liquid chromatography on optically active columns.13,14 The stereochemistry was determined by comparing their chiroptical properties with those of chiral selenoxides with known absolute configurations. The stability of the chiral telluroxides toward racemization was found to be lower than that of the corresponding selenoxides, and the racemization mechanism that involved formation of the achiral hydrate by reaction of water was also clarified. Telluroxides 4 and 5, which were thermodynamically stabilized by nitrogen-tellurium interactions, were also optically resolved and their absolute configurations and stability were studied (Scheme 2).12,14... 

On the other hand, telluronium imides 13 were isolated for the first time in 2002 by optical resolution of their racemic samples on an optically active column by medium-pressure column chromatography.27 The relationship between the absolute configurations and the chiroptical properties was clarified on the basis of their specific rotations and circular dichroism spectra. The racemization mechanism of the optically active telluronium imides, which involved the formation of corresponding telluroxides by hydrolysis of the telluronium imides, was proposed (Scheme 6). 

In contrast to benzyl p-tolyl sulfoxide 37, allyl p-tolyl sulfoxide 217 racemizes between 50 and 70°C. The values of the activation energy and the entropy (A/f = 23 kcal/mol AS = -4.9 e.u.) as well as the absence of decomposition products are indicative of a different racemization mechanism for this sulfoxide. In this connection, it is interesting to note that the condensation of p-toluenesulfenyl chloride with allyl alcohol labeled in the a-position with deuterium... 

It has not been easy to use AV values to support a racemization mechanism, nor indeed to rationalize AK in terms of known mechanisms. For racemization, AV° is zero and to a first approximation AV might also be expected to be near zero for a twist mechanism. For both Cr(phen)3 and Nifphenlj however AV values are near zero, although the... 

In the first step, a cyclic intermediate is generated by a suprafacial addition, followed by a SN2-type ring opening (e.g., halogenation or epoxidation ring opening). In this manner, olefin 1 may either be converted into diastereomer 2 or 3, which may be optically active or racemic. Mechanism control thus means that the relative, but not the absolute, configuration of the two vicinal centers is defined. 

Tbe dissymmetry would thus be lost, and when the chelate ring reforms, it would have a 50-50 chance of producing either the A or A isomer (Chapter 12). Since the rate-determining step in this mechanism is the dissociation of the ligand, the rate of racemization (kr) would have to equal the rate of dissociation (kj). For example, tris(pbenanthroline)rnckel(II) racemizes at the same rate (kr — 1.5 x 104 s l) as it dissociates (kj = 1.6 x 104 s l), which implies dissociation is part of the racemization mechanism. If racemization takes place faster than dissociation (as it does, e.g., for tris(phefianthroline)iron(lI) k,. — 6.7 x 1CT4 s 1 and kd = 0.70 x JO 4 s1], ibis mechanism can be eliminated. 

Scheme 2 Racemization Mechanism of Aldehydes through Keto-Enol Tautomerism1"1...

A stereochemical study of the synthesis of unsaturated 1,4-aminoalcohols via the reaction of unsaturated 1,4-alkoxyalcohols with chorosulfonyl isocyanate revealed a competition between an retentive mechanism and an SnI racemization mechanism, with the latter having a greater proportion with systems where the carbocation intermediate is more stable.254 An interrupted Nazarov reaction was observed, in which a nonconjugated alkene held near the dienone nucleus undergoes intramolecular trapping of the Nazarov cyclopentenyl cation intermediate.255 Cholesterol couples to 6-chloropurine under the conditions of the Mitsunobu reaction the stereochemistry and structural diversity of the products indicate that a homoallylic carbocation derived from cholesterol is the key intermediate.256 l-Siloxy-l,5-diynes undergo a Brpnsted acid-promoted 5-endo-dig cyclization with a ketenium ion and a vinyl cation proposed as intermediates.257... 

Fig. 7 Proposed racemization mechanism for the assembly the spacer units are rotated in a concerted manner until the symmetric intermediate b is reached...

Figure 12.12 Proposed racemization mechanism of hydantoin racemase using a two-base mechanism. The hypothetical character of the intermediate structure is indicated by the dashed lines surrounding the figure.

Carbodiimides have chiral structures similar to allenes, i.e., they can exist in optically active forms. Schloegl and Mechtler were the first to report a partial optical separation of N,N"-diferrocenylcarbodiimide into enantiomers by chromatography on acetylated cellulose, but other authors doubt the validity of these results. According to theoretical calculations a separation of carbodiimide enantiomers is not possible. N,N -diferrocenylcarbodiimide was also obtained in optically active form by kinetic resolution in the reaction with (-)-S-6,6"-dinitrodiphenic acid. Cervinka and coworkers isolated both enantiomers of (R,S)-N,N"-bis(o -phenylethyl)carbodiimide, and they found that they undergo racemization at room temperature. A recent study on the racemization mechanism of macrocyclic carbodiimides indicates that the open chain as well as the large ring carbodiimides racemize by nitrogen inversion or tra 5-rotation, while medium size cyclic carbodiimides racemize by cw-rotation. ... 

NMR and CD methods. (251) From the spectral data it is concluded that these complexes stereospecifically adopt the A-s-cis form(s) in solution [48]. The solution structures of a variety of EDTA-type complexes have been deduced from variable temperature studies. (306) Racemization of Ni(EDTA) and Ni(l,3-DDTA) is rapid at 80°C but is slow for the other complexes studied. The kinetic data indicate predominant 5-coordination by EDTA and 1,3-PDTA. The suggested racemization mechanism (Fig. 5) involves a 7-coordinate intermediate. 

FIG. 5, Suggested solution structure and racemization mechanism of the Ni-EDTA complex in aqueous solution. (306)... 

Figure 6. An intramolecular bond rupture racemization mechanism ...

The more we examined the racemization of 9 and 10 b, the more interesting aspects emerged. When 10 b was stirred under the resolution conditions (excluding lipase) for 66 h in a system where 97-98% of all acidic protons were composed of deuterium, the ee of the isolated 10b was 77.0% (23% racemization) and the side-chairi s a-ester methylene carbon was 14% deuterated (by JHNMR). As this is opposite to that intuitively expected, it may be that the racemization mechanism is assisted by an unusual ex-... 

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