Frozen chirality

The chiral crystallization of achiral materials and the asymmetric transformation in the chiral crystal environment are described. Many successful examples are presented however, it is still rare to find materials which show this behavior. Recently, new asymmetric reactions using chiral crystals in homogeneous conditions have been developed. [39],[40] These reactions used the frozen chirality generated by chiral... 

Sakamoto, M., Iwamoto, T., Nono, N., Ando, M., Arai, W., Mino, T., and Fujita, T. (2003) Memory of Chirality Generated by Spontaneous Crystallization and Asymmetric Synthesis Using the Frozen Chirality, J. Org. Chem., 68, 942-946. 

The dimerization of thioformylketene was investigated by B3LYP and G3MP2B3 methods. The 4 + 4-pathway has the lowest energy barrier and calculations suggest that the reaction is pseudopericyclic.231 The stereospecific intramolecular 4 + 4-cycloaddition reaction between cyclohexadiene iron tricarbonyl complex and appended dienes (198) generates cyclooctadiene tricyclic adducts (199) (Scheme 56).232 The first example of an asymmetric intermolecular 4 + 4-photocycloaddition reaction in solution between 9-cyanoanthracene and chiral 2-methoxy-l-naphthamides has been reported. The frozen chirality is effectively transferred to the optically active product.233... 

Recently, Sakamoto et al. reported an absolute asymmetric synthesis using the frozen chirality generated by chiral crystallization. Achiral asymmetricly substituted imide 68, which bonds between the nitrogen atom and the tetrahydronaph-tyl (TENAP) group, rotates freely at room temperature, crystallized in a chiral fashion, and the enantiomerization owing to the bond rotation was suppressed at low temperature (Scheme 33). Furthermore, the frozen molecular chirality could be transferred to optically active products in fluid solution [35]... 

Memory of chirality generated by spontaneous crystallization and asymmetric synthesis using the frozen chirality. J. Org. Chem., Vol. 68, pp. 942-946... 

The conformational kinetic control of the chiral centres present in a molecule may be exemplified by the rran -diaxial opening of an epoxide i rf a polycyclic system [7]. In this case, the less stable conformation is also "frozen" by forming an auxiliary lactone bridge, which reverses temporarily the conformations of the rings and the substituents. 

Erythronolide A (8) is a 14-membered macrolide, with ten chiral centres. Because a 14-membered ring is not only as flexible as a linear open-chain, but also prone to experience several kinds of transannular interactions, any kind of stereochemical control must be exerted in the corresponding open-chain derivative,20 i.e. in the seco-acid 9, or in the linear fragments resulting from its disconnection, which should be immobihsed or "frozen" in someway. 

The reactions with nG-105 dendrimers show a different trend. Enhanced catalytic performance was observed with increasing dendrimer generation (77.3% yield, 97.2% selectivity, 15.5% ee for Gl 85% yield, 98% selectivity, 37% ee for G4). This comparison indicates that the introduction of an alkyl spacer not only facilitates the access of reactant to the catalytic active sites but also prevents the formation of frozen-in conformations and thus different chiral active sites. However, when the fifth-generation dendrimer is reached, the multiple interactions between end groups become more pronounced, which leads to a decrease in the catalyst performance (68% yield, 95.3% selectivity, 17.6% ee). 

The mesityl complex [(mes)Os(C2H4)(CH3CN)] results in addition of benzene when irradiated with ultraviolet light in benzene solution (Fig. 19) [103]. Photolysis of the complex in perdeuterotoluene in frozen matrices results in D atom abstraction. Photolysis of Os(VI) dioxo complexes such as [0s(0)2(Bu-salch)] (Scheme 1) with olefins yields epoxides, in one instance with some degree of chiral selectivity [104],... 

Absolute asymmetric synthesis was observed in the solid-state photoreaction of benzoylbenzamide 59 to phthalide 60 however, the reaction mechanism was completely different from that of thioester 57. [35] Recrystallization of these amides 59a-c from the chloroform-hexane solution afforded colorless prisms in all cases. X-ray crystallographic analysis revealed that all prochiral amides 59a-c adopted orthorhombic chiral space group P2 2 2 and were frozen in chiral and helical conformation in the crystal lattice. 

It is of great significance to correlate the absolute configurations of helical molecules frozen in the chiral crystalline environment with the sign of specific rotations. An attempt to determine the absolute configuration of (+)-57a giving rise to a positive... 

The experimental observation was that C2-symmetric metallocene complexes of zirconium (Fig. 6) produced isotactic polymers, while Cs-symmet-ric metallocene complexes (Fig. 6) produced syndiotactic polymers. Pure MM calculations with frozen core showed that the stereoselectivity is not related to direct interactions of the -ligands of the chiral metallocene with the entering monomer, but to interactions of the -ligands with the growing chain. It is therefore the chirally oriented growing chain which discriminates between the prochiral faces of the propene monomer. For C2-symmetric complexes, identical enantiofacial orientation in all insertion steps results in isotactic polymer formation for Cs-symmetric complexes the enantiofacial orientation alternates between insertion steps and leads to syndiotactic polymers. 

Coumarin photochemistry has been recently employed to demonstrate that a frozen axial chirality can be used to induce the absolute configuration of stereogenic centers. Coumarin 103 was obtained as a single atropisomer by spontaneous crystallization (Scheme 6.37). Upon warming powdered crystals of 103 in MeOH to —20 °C, sensitized [2 + 2]-photocydoaddition to ethyl vinyl ether gave the almost enantiomerically pure products 104. The approach to the coumarin double bond occurred preferentially from the less-shielded face to which the amide carbonyl group... 

In a typical reaction, a solution of the antibody in phosphate buffered saline (PBS) is added to a solution of the racemic substrate (ca. 50-100 mM) in either toluene or chlorobenzene. The mixture is shaken, while the substrate ee is monitored by chiral HPLC. When the desired ee is reached, the reaction mixture is cooled (—20°C), allowing easy separation of the organic layer from the frozen aqueous antibody solution. The aldol product is purified by column chromatography, and the antibody solution is thawed for reuse. 

The phosphorane (70) shown in Scheme 8 is analogous to (65) discussed in Scheme 7, except that the dimethyl-compound (70) lacks the chiral center in one of the ring carbons,77 which is present in (65). The n.m.r. spectrum of (70) shows77 two methoxy signals at — 8°, but only one such signal at ca. +62. The interpretation of the data is quite simple below certain temperatures, (70) exists as two frozen isomers, (70-(l 4) (2 5))... 

Appendix) provide an example of frozen rotation with three different substituents. Without the bridge, however, the barrier of rotation for bent bis(tetrahydroindenyl)metaUocenes is Ukely to be too small to justify classification as a chiral system. 

Coordinated thioether S is often asymmetric. In (302) the asymmetry is frozen by the configuration of the attached chelate rings but in (301) it is not and inversion is fast. Conventional resolution via diastereoisomeric salts has never been substantiated for a purely enantiomeric Co—SR Ril+ system devoid of other chirality. I3C and H studies on diastereoisomeric systems1079 however show that inversion rates are normally of the order 0.1-10 s1, which makes coordinated thioethers decidedly more configurationally labile than organic sulfonium salts. The effects of asymmetry in (302) are readily seen in diastereoisomeric systems where the lone pair on S is often stereospecifically orientated. It usually directs stereochemical change and ligand replacement processes. 

FIG. 12. The / -mandelic acid (in gold)-based chiral auxiliary at 0-2 can form a more-stable 6-membered dioxolenium ion, frans-decalm-like (32.9 kJ mol-1 relative to its BO), whereas its epimer can lead to a cw-decalin type of dioxolenium ion (72.8 kJ mol-1), ADF-DFT (DPZ frozen core). The trans-decalin leads to a glycosides, whereas the cw-decalin leads to / glycosides. Both 6-membered-ring dioxolenium ions are more stable then any dioxolenium ion based on participation from 0-3 (R 43.9 kJ mol-1 and 5 46.7 kJ mol-1). If R = allyl, then it is hypothesized that non-facially selective glycosylation takes place through the oxacarbenium ion (BO or Bl). Note that the experiment used O-benzyl and not the O-methyl, which was used for the calculation to avoid complications of multiple minima. 

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