Diastereomeric energy differences

It was considered that the optically active polyamines interact more strongly with the acid chloride or anhydride than acid salt. Accordingly higher optical yield was anticipated in the products. However, only slight enantiomer selection was observed in reactions (3) or (4). The diastereomeric energy difference is apparently too small to differenciate the enantiomeric acid chloride or anhydride. 

Preparation of enantiomerically enriched materials by use of chiral catalysts is also based on differences in transition-state energies. While the reactant is part of a complex or intermediate containing a chiral catalyst, it is in a chiral environment. The intermediates and complexes containing each enantiomeric reactant and a homochiral catalyst are diastereomeric and differ in energy. This energy difference can then control selection between the stereoisomeric products of the reaction. If the reaction creates a new stereogenic center in the reactant molecule, there can be a preference for formation of one enantiomer over the other. 

The T-conformation had two prevalent conformers 88 and 89 where the steric bulk of the 4-fluorophenyl group blocks the P-face of the oxonium ions (Scheme 7.27). Reduction occurs from the less hindered a-face on each conformer leading to the diastereomeric mixture of products. Since there was only a O kcalmoT1 energy difference in these lowest energy conformers 88 and 89, this nicely supported the observed product distribution of approximately 3 1 of 18 19 under the best reaction conditions. 

This rather amazing result at first seems impossible. As indicated in Figure 8.37, the ShiCaPf structure is composed of heterochiral adjacent layer pairs. By pure symmetry it must be the case that the unichiral molecules have a lower free energy in either the (+) or the (—) layers. The free-energy difference between these diastereomeric layer structures could be small. But, the layers possess a collective free energy. A priori it is expected that the thermodynamic phase would possess only layers of the lower free-energy chirality. 

Effect of two methyl groups in the 3- and 3 -positions (1284) compared with (2851) on the free energy differences between diastereomeric complexes"... 

It should come as no surprise that a chapter dealing with asymmetric catalysis should mention resolutions. Resolutions depend primarily on the solubility differences of disastereomers in the ground state. X-Ray analyses of diastereomeric salts (4,3) appear to point to a best-fit structure for the least soluble salt. Success in asymmetric catalysis depends on free-energy differences between disastereomeric transition states. When these energy differences approach 2 kcal/ mol, resulting in an e.e. of 93% at 23°C, the favored complex, although the result of a termolecular reaction, shows the best-fit characteristics typical of a diastereomeric salt. 

These reactions, performed many times, show, in addition to the reversal of the absolute configuration of the product with the change in the configuration at C-8 and C-9 of the alkaloids, a small but reproducible difference in the e.e. of the product. It is evident that the diastereomeric nature of quinine vs. quinidine and cinchonidine vs. cinchonine expresses itself via small but important energy differences in the best fits of the transition states. Noteworthy in this respect is the fine work of Kobayashi (20), who observed larger differences (in the e.e. s of products) when the diastereomeric cinchona alkaloids were used as catalysts after having been copolymerized with acrylonitrile (presumably via the vinyl side chain of the alkaloids). 

II(S)) and/or to a different reaction rate of the two diastereomeric 7r-olefin complexes to the corresponding diastereomeric alkyl-rhodium complexes (VI(s) and VI(R)). For diastereomeric cis- or trans-[a-methylbenzyl]-[vinyl olefin] -dichloroplatinum( II) complexes, the diastereomeric equilibrium is very rapidly achieved in the presence of an excess of olefin even at room temperature (40). Therefore, it seems probable that asymmetric induction in 7r-olefin complexes formation (I — II) cannot play a relevant role in determining the optical purity of the reaction products. On the other hand, both the free energy difference between the two 7r-olefin complexes (AG°II(S) — AG°n(R) = AG°) and the difference between the two free energies of activation for the isomerization of 7r-com-plexes II(S) and II(R) to the corresponding alkyl-rhodium complexes VI(s) and VI(R) (AG II(R) — AG n(S) = AAG ) can control the overall difference in activation energy for the formation of the diastereomeric rhodium-alkyl complexes and hence the sign and extent of asymmetric induction. 

In this case a thermodynamic and/or a kinetic factor can control the overall difference in the activation energy and hence the diastereomeric composition of the alkyl-rhodium complexes and the asymmetric induction. The thermodynamic factor is the energy difference AG°C between the two conformers (XII a) and (XII b) the kinetic factor is the difference between the free energy of activation AAG C of the reaction leading from each conformer to the corresponding alkyl-rhodium complex. 

You will notice that the reaction products 23 and 24 are diastereomers, not enantiomers. Asymmetric synthesis can be achieved only when the possible transition states for reaction are diastereomeric because they then will have different energies and will lead to products at different rates. The larger the energy difference between diastereomeric transition states, the more stereochemical preference there will be for one chirality over the other. 

Equally disappointing were the results obtained employing the Fe(III) catalyst 172 for the oxidation of prochiral sulfides [115]. Though the yields observed were up to 88% the maximal ee was only 48%. From these studies it appears that the more reactive substrates display the lowest ee, pointing to smaller energy differences in the diastereomeric transition states which are expected to be early on the reaction coordinate. 

Dimethyloxazolidines have been utilized as chiral auxiliaries for the diastere-oselective functionalization of the optically active tiglic acid derivatives by means of epoxidation with dimethyldioxirane (DMD) or m-CPBA and ene reactions with 02 or 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). In the DMD and m-CPBA epoxidations, high diastereoselectivities but opposite senses of diastereomer selection was observed. In contrast, the stereochemistry of the 102 and PTAD ene reactions depended on the size of the attacking enophile whereas essentially perfect diastereoselectivity was obtained with PTAD, much lower stereoselection was observed with 02. The stereochemical results for the DMD and m-CPBA epoxidations and the PTAD ene reaction are explained in terms of the energy differences for the corresponding diastereomeric transition states, dictated by steric and electronic effects.200... 

The optimized structures of the diastereomeric catalyst-enamide complexes with the enamide bonded from its pro-R and pro-S faces have very similar structures to their nitrile counterparts. The calculated free energy difference between these two diastereomers is practically zero (0.07 kcal/ mol). 

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