Racemization barriers

The first optically active example was 117 ([a]D + 71 ° in ethanol through its brucine salt) for which a racemization barrier of 113 kJ mol-1 was found 127). In order to establish the mode of racemization the optically active derivatives, 118 and 119 were prepared through their cinchonidine and brucine salts, respectively ([a]D —21 and —78°, respectively)128), From racemization experiments with the methylesters of 118 and 119 (with barriers of 130 and 105 kJ mop1, respectively) it could be concluded that a biradical rearrangement predominates in 118, whereas for 117 and 119 a simple ring inversion process is in accordance with the results 128). 

TABLE 4. Relation between C—X bond lengths and racemization barriers for compounds 17a-17c and 17e85... 

Tab. 2 Racemization barriers in overcrowded alkenes 23 with different bridging moieties X and Y.

Table 2 summarizes the racemization barriers in unsubstituted chiral alkenes 23 with different bridging moieties in their upper and lower halves. As is evident from these data, the tetrahydrophenanthrene-type upper part is large enough to prevent fast racemization by movement of the aromatic moieties of upper and lower halves through the mean plane of the molecule. On the other hand, there is enough conformational flexibility in the molecules to prevent excessive distortion of the central olefmic bond (leading to ground state destabilization), which would lower the racemization barrier. 

Based on their fluorination protocol, Cahard and co-workers have elaborated a convenient synthesis of a-fluoro-a-phenylglycin derivatives [18]. For example, upon reaction with reagent 24 racemic nitrile 23 was converted into the fluorinated derivative 25 with 94% enantiomeric excess. The corresponding ester derivatives of 23 gave rise to somewhat lower ees. This difference was contributed to the fact that a-lithiated nitriles can be in equilibrium with axial-chiral lithio ketene imines of low racemization barriers thus leading to a potential dynamic kinetic resolution. 

Whereas the rapidly equilibrating mixture of diastereomers 63 B,B was optically stable at room temperature, racemization occured when solutions in toluene were heated for several hours. A kinetic study revealed a racemization barrier of AG 8 = 27.6 2 (115.7. + 8.2) kcal(kJ)/mol, for which high energy Berry processes running through the decisive, achiral trigonal-bipyramidal transition states 66, 67 with diequatorial 2,2 -biphenylylene ligands were made responsible 74). Equivalent... 

In addition to probing the effect of nonplanarity on the antiaromatic character of these phenanthrene-based systems, it is also possible to analyze the effect of charge on their racemization barrier. This can be achieved by studying systems like 4-isopropyl-1,5,8-trimethylphenanthrene (ll)38. The diastereotopic isopropyl marker at the bay region position C4 yields a free-energy barrier (AG ) of 22.2 kcalmol-1 for the racemization process of the neutral compound and 15.4 kcalmol-1 for the racemization of the dianion (ll2-). Although the barrier of racemization decreases as a result of reduction, the system still maintains its helicity. 

Figure 3.5. Determination of racemization barrier of the enolate generated from 40 and KHMDS. ee° The ee value of 41 obtained by the reaction of the enolate immediately after its generation (t = 5 min) from 40 with methyl iodide, ee1 The ee value of 41 obtained by treatment of 40 with KHMDS for the time indicated, followed by addition of methyl iodide. 0.25 mmol of 40 was employed for each run. Reactions were quenched 30 minutes after the addition of methyl iodide in order to minimize racemization of the enolate intermediate during alkylation ee° = 80% (t = 5 min), ee1=3° 111111 = 79%, 1=90 111111 = 76%, eet=m = 74%, eet=42° = 63%, eet=12° = 56%, 1=1440 111111 = 37%.

Feringa et al.109 succeeded in resolving thioxanthene-type alkenes. A high racemization barrier (AG = 114.1 kJmol1) was found for 2,2 -dimcthylbithi-oxanthylidene (237), compared to values reported for other bis(tricyclic) alkenes (AG = 50-92 kJ mol"V8 109-112... 

The thermal racemization and the resolution of cis-trans isomers of benzoannellated bithioxanthylidene derivatives which show a stereospecific thermal isomerization process have been achieved.113 The study of the thermal isomerization of the unsubstituted bithioxanthene 238 by polarimetry at 75-85°C inp-xylene, led to a racemization barrier of 119.5 kJmol -. ... 

B. L. Feringa, W. F. Jager, and B. De Lange, Resolution of sterically overcrowded ethylenes a remarkable correlation between bond lenghts and racemization barriers, Tetrahedron Lett. 33, 2887-2890 (1992). 

Table 10, Comparison of racemization barriers of methyl-substituted helicenes with helicenes... 

The isolated forms presented strongly solvent and concentration dependent optical rotations. The racemization barriers of the tetramethyl 69 and tetraethyl 70 analogues were determined in 0.1 N NaOH solution by polar-imetry. The resulting barriers were equal to 115.8 and 133.3 kj mol , respectively. The origin of the barrier difference is enthalpy driven and results from the larger steiic size of the ethyl group compare to the methyl group. 

These new data bring additional evidence that the racemization barrier is independent of the steric contribution of the ortho substituent in the series free methyl, buttressed methyl and locked methyl (1-naphthyl). Such a behavior cannot account for a racemization process involving a simple rotation around the pivot bond. 

As mentioned previously, conformational changes of TOT in solution have demonstrated the considerable flexibility of the molecule. This result, based upon temperature-dependent NMR signals, has further confirmed the fairly rapid interconversion between the P- and M-propeller configurations via helical conformations , over a low racemization barrier of about 21 kcal moU. It stands to reason that NMR measurements in solution fail to get information on TOT host-guest interactions. With the advent of solid-state NMR the record of high... 

The choice of the IV-protec ting group (Al-Boc) proved to be critical for achieving a high enantiomeric excess of the cyclization reaction. In contrast to KHMDS, lithium amide bases (LHMDS or LiTMP) did not afford detectable quantities of the anticipated heterocycles. The mechanism of asymmetry transfer was proposed to rely on the formation of axially chiral nonracemic enolate (eq 66) with a chiral C-N axis, the racemization barrier for which was found to be 16.0 kcal mol. ... 

A family of Cu and Ag double-stranded helicates with nuclearity ranging from 2 to 5 has been reported (Figure 18). Each metal center is chelated by two bidentate units from different ligand strands in pseudotetrahedral geometry. The helicates exist as racemic mixtures of P and M isomers. The dinuclear racemates have a high racemization barrier of over 21 kcal mol for the... 

The presence of diastereotopic hydrogen atoms on the methylene carbons of 24 and 25 also provided opportunities to determine the activation barriers for racemi-zation. A barrier of 15.3 kcal/mol was determined for 24, whereas that of 25 is too high to be determined by variable-temperature NMR studies. It was estimated that the activation barrier for racemization is larger than 21.1 kcal/mol for 25. The similarity in the rotational barriers of 24 and 25 but very different racemization barriers suggest a molecular movement in which the phenyl groups turn around each other like cog wheels for racemization. 

Sulfoxides are pyramidal molecules, and typically they are stably chiral, with racemization barriers on the order of 40 kcal/mol. However, the sulfoxide shown has a racemization barrier of only 21 kcal/ mol. Explain this observation. 

The rates of racemization of the carbon center over the temperature range of 37-52°C provided an enthalpic value of A// (racemization) = 32.5 1.5 kcal/mol. Assuming the carbon radical has a very low racemization barrier [23], the calculated (racemization) should reflect the activation enthalpy for homolysis of the Rh-C bond. Should the radical recombination barrier for Rh(Il) mirror the value reported for Co(II) systems (ca. 2 kcal/mol) [24, 25], an Rh-C bond dissociation energy (BDE) of approximately 31 kcal/mol can be estimated. 

Molecule Terminal ring centroid distance (A) Terminal ring interplanar angle n Inner helix climb (A) Inner helix in-plane turn (") Racemization barrier (kcal moM) Helical strain (kcal mol )... 

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