Dynamic stereomutation

In the kinetic resolution, the yield of desired optically active product cannot exceed 50% based on the racemic substrate, even if the chiral-discriminating ability of the chiral catalyst is extremely high. In order to obtain one diastereomer selectively, the conversion must be suppressed to less than 50%, while in order to obtain one enantiomer of the starting material selectively, a higher than 50% conversion is required. If the stereogenic center is labile in the racemic substrate, one can convert the substrate completely to gain almost 100% yield of the diastereomer formation by utilizing dynamic stereomutation. 

The dynamic NMR (DNMR) spectroscopy has been used in studies of stereomutations of non-symmetrical di-Schiff bases [18].39 It was shown that the hindered Schiff bases exist in DMSO in two chiral conformations. The presence of a pair of conformers being in equilibrium was explained by the existence of two stereogenic axes a g (aligned to Cl—N8 bond) and a 7 (aligned to C6—N7 bond) due to restricted rotation around two Ar—N bonds. The trans to cis interconversion as well as enantio- or diastereoisomerisation barriers for the compounds studied have been established using line shape analysis. 

Figure 20.1. A computationally inferred lapsed-time sequence of structures representing reaction dynamics for a thermal stereomutation of cyclopropane. [Reproduced with permission from J. A. Horsley, Y. Jean, C. Moser, L. Salem, R. M. Stevens, and J. S. Wright, J. Am. Chem. Soc. 1972, 94, 279. Copyright 1972 American Chemical Society.] Reproduced with permission from Y. Jean, L. Salem, J. S. Wright, J. A. Horsley, C. Moser, and R. M. Stevens, Pure Appl. Chem. Suppl. (23rd Congr., Boston) 1971, 1, 197.

The combination of Ru complex-catalyzed stereomutation of secondary alcohols with enzyme-catalyzed enantioselective acylation is an efficient procedure to obtain chiral acyloxy compounds with excellent optical purity from a variety of racemic secondary alcohols via dynamic kinetic resolution [112]. 

Doubleday, C. Bolton, K. Hase, W. L. Direct dynamics quasiclassical trajectory study of the thermal stereomutations of cyclopropane, J. Phys. Chem. A 1998, 102,... 

Dynamic phenomena of this type might play a role in the vinylcyclopropane rearrangement, and would, for example, explain the apparent excess double inversion seen by Gajewski and Warner (Section III.C.3) in the racemization of (R,R)-trans-2-meihy -l-(3,3-dimethyl-l-buten-l,l-d2-2-yl) cyclopropane, without the need to postulate separate mechanisms for stereomutation and rearrangement. There is also some evidence for incursion of dynamic effects in the deazetization of pyrazolines (Section III.G). 

Related results of promotion (catalysis) and inhibition of stereomutation by vibrational excitation have also been obtained for the much larger molecule, aniline-NHD (C H NHO), which shows short-time chirality and stereomutation [104. 105]. This kind of study opens the way to a new look at kinetics, which shows coherent and mode-selective d5mamics, even in the absence of coherent external fields. The possibility of enforcing coherent dynamics by fields ( coherent control ) is discussed in chapter A3.13. 

We therefore can illustrate the process of the stereomutation as the movement of a point mass in a one-dimensional double minimum potential with a low barrier (Fig. 3.4). The real stereomutation dynamics take place in a six-dimensional space. 

These states are time dependent. The quantum dynamics of the stereomutation as also the quantum dynamics of atoms and molecules in general is described through the time-dependent Schrodinger equation (with i = V )... 

Semiempirical direct dynamics was used to study trimethylene s unimo-lecular dynamics and the thermal stereomutation of cyclopropane.The semiempirical model used in these simulations is AMI with specific reaction parameters (SRPs see discussion of semiempirical electronic structure theory in the section on BO direct dynamics) chosen to fit the CASSCF PES. In choosing the SRPs, the AMI barrier for propene formation was lowered by... 

Additional work needs to be done to develop a theoretical model to represent the trimethylene kinetics. The dynamics in the trimethylene region of the potential energy surface is neither statistical nor direct, and instead contains both these elements. Future work on the kinetics of cyclopropane stereomutation will include developing a theoretical model for trimethylene s dynamics, assessing the accuracy of assuming RRKM dynamics for cyclopropane, and determining a more accurate PES for trimethylene. 

Dynamics Simulation of the Stereomutation of Cyclopropane C. Doubleday, Jr., K. Bolton, and W. L. Hase, J. Phys. Chem. A, 102, 3648 (1998). Direct Dynamics Quasiclassical Trajectory Study of the Thermal Stereomutations of Cyclopropane. 

D Acquarica I, Gasparrini F, Pierini M, Villani C, Zappia G. Dynamic HPLC on chiral stationary phases a powerful tool for the investigation of stereomutation processes. J Sep Sci 2006 29 1508-1516. 

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