Chiral configurational stability

Hawkins J M, Nambu M and Meyer A 1994 Resolution and configurational stability of the chiral fullerenes C-g, C g, and Cg. A limit for the activation energy of the Stone-Wales transformation J. Am. Chem. Soc. 116 7642-5... 

Nucleophilic substitutions of 0-activated 2-hydroxy carboxylic acids and esters, respectively, are well established, but little is known about the analogous reactions of activated cyanohydrins. Chiral 2-sulfonyloxynitriles, accessible from non-racemic cyanohydrins, have a relatively high configurational stability. They react with nucleophiles under very mild conditions under inversion of configuration (Scheme 8). ° ... 

In a related study, Rieke and Guijarro studied the configurational stability of the zinc-carbon bond in 2-butylzinc bromide and (l-phenylprop-2-yl)zinc bromide, using a bis(oxazoline) as a chiral resolving agent.72 From their data, the authors determined the A 6 of inversion at the secondary carbon of (l-phenylprop-2-yl)zinc bromide to be 113.8 kj mol-1. 

FIGURE 4. Configurational stability of chiral organostannanes according to H NMR analysis of diastereotopic methyl signals... 

The experimentally observable phenomenon of optical activity is usually considered in the context of variation of molecular chirality arising from a particular stereochemical configuration at a particular atom such that the molecule has no improper rotation S axis. Molecules with opposite chirality configurations are enantiomers and show oppositely signed optical activity. Molecules differing only in conformation are called conformers or rotational isomers. In most cases, the difference in energy between rotational isomeric states is very small, such that at ambient temperature all are populated and no optical activity results. However, if one particular conformer is stabilized, for example, by restriction of rotation about a bond, the molecule can become chiral, and thus optically active. 

The configurational stability of chiral allenylmetal reagents depends to a large extent on the nature of the metal substituent. The mechanism of the racemization process has not been studied in detail, but two reasonable pathways can be proposed, based on known reactivity characteristics of these compounds. The first entails reversible intermolecular SE- rearrangement to the propargylic isomer. This process could proceed by a pure syn or anti pathway, in which case no racemization would take place. However, the occurrence of both pathways would result in racemization (Scheme 9.5). 

An extensive review appeared on the configurational stability of enantiomeric organolithium reagents and the transfer of the steric information in their reactions. From the point of view of the present chapter an important factor that can be evaluated is the ease by which an inversion of configuration takes place at the metallation site. It happens that H, Li, C and P NMR spectra of diastereotopic species have been central to our understanding of the epimerization mechanism depicted in equation 26, where C and epi-C represent the solvated complex of one chiral species and its epimer, respectively. It has been postulated that inversion of configuration at the Li attachment site takes place when a solvent-separated ion pair is formed. This leads to planarization of the carbanion, its rotation and recombination to form the C—Li bond, as shown in equation 27, where Li+-L is the solvated lithium cation. An alternative route for epimerization is a series of... 

Enantiomerically pure a-lithiated ethers have been prepared from stannanes and turned out to react with electrophiles under retention. The configurational stability of the hthium carbenoid 19 has been deduced from equation 10 . Lithiated benzyl methyl ether, chelated by a chiral bis(oxazoline) ligand, proved itself to be configurationally stable as welP . ... 

The closely related a-(pyrid-2-ylthio)benzyllithium (257) has a higher configurational stability, and equilibration with the chiral ligand prior to the substitution step is required , indicating that a dynamic thermodynamic resolution is important (equation 61). Depending on the method of calculation, (7 )-257 255b was found to be by 1.42 to 1.92 kcalmoD ... 

Increasing the steric bulk in the 3-position led to dramatic enhancement of the configurational stability for the fert-bntyl derivative 426c, a complete chirality transfer occnrred . Some epimerization took place with the 3-cyclohexylalkynyl carbamate . ... 

Asymmetric oxidation of prochiral sulfides is one of the most effective routes for the preparation of chiral sulfoxides. These latter molecules attract great interest, as they are useful synthons for some drugs. They can also be used as chiral auxiliaries due to their configurational stability. The oxidation can be performed by using complexes... 

The synthesis of functionalized zinc organometallics can be accomplished with a variety of methods that have been developed in recent years. The intrinsic moderate reactivity of organozinc reagents can be dramatically increased by the use of the appropriate transition metal catalyst or Lewis acid. Furthermore, the low ionic character of the carbon-zinc bond allows the preparation of a variety of chiral zinc organometallics with synthetically useful configurational stability. These properties make organozinc compounds ideal inteimediates for the synthesis of complex and polyfunctionalized organic molecules. 

Interesting solutions to the spontaneous epimerization of C2-substituted malonyl residues, to provide configurational stability, were explored independently by Dal Pozzo and Laurita 111 and Abouabdellah and Welch. 30 Replacement of the C2 hydrogen in C2-alkyl-substituted malonyl residues by either methyl 111 or fluorine 30 stabilized the configurational integrity of the C2 chiral center in the malonyl derivatives. 

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