Asymmetric solvent effects

Torrie, G. M. and Patey, G. N. Molecular solvent model for an electrical double layer asymmetric solvent effects, J.Phys.Chem., 97(1993). 12909-12918... 

G. M. Torrie and G. N. Patey, /. Phys. Chem., 97,12909 (1993). Molecular Solvent Model for an Electrical Double Layer Asymmetric Solvent Effects. 

Collins and coworkers applied the bis(tetrahydroindenyl)zirconium triflate 32, which is used as a polymerization catalyst, to the asymmetric Diels-Alder reaction [50] (Scheme 1.61). A remarkable solvent effect was observed - although only a low optical yield was obtained in CH2CI2, high optical purity (91% ee) was realized in 2-nitropropane by use of only 1 mol% of the catalyst. The catalyst is also effective for crotonoyloxazolidinone, giving the cycloadduct in 90% ee. 

They demonstrated that the C2-symmetric bis-benzothiazine (R,R)- 91 was an effective ligand in the asymmetric allylic alkylation reaction. The best result in this case was the reaction of 198 and 199 in the presence of BSA, Pd2(dba)3 and (/ ,/ )-197, which gave the product (S)-200 in 75% yield and 86% ee. More experimental data revealed that solvent effects are very important in this reaction (Scheme 57). Relatively nonpolar solvents resulted in good yields and enantiomeric excesses while reaction in CH3CN and CH2CI2 gave only racemic products in moderate yields (Table 8). 

Otto et al. studied asymmetric Diels-Alder reactions in the presence of the copper salts of glycine, L-valine, L-leucine, L-phenylalanine, L-tyrosine, l-tryptophan, and /V-a-L-tryptophan (L-abrine). The copper salt of L-abrine gave the highest enantioselectivity. Table 5 3 compares the solvent effect in this reaction, and clearly water is the best solvent among the solvent systems studied. 

A characteristic solvent effect on the asymmetric induction is observed. 

Structural and Solvent Effects in the Asymmetric Induction of Chalcone Epoxides... 

As is the case in all other quinine-catalyzed reactions, the quininium-salt-catalyzed phase-transfer reactions are subject to strong solvent effects (Table 8) (81). The fact that, in the presence of water, polar solvents lower the e.e., whereas apolar solvents raise the e.e., indicates that these are true phase-transfer reactions in which the ion pairs within the organic layer are responsible for the asymmetric induction. 

A marked solvent effect on the sense of asymmetric induction was observed. For example, reduction of acetophenone with 65 in refluxing ether gave the (R)-alcohol in 48% optical yield, and reduction in boiling THF gave die (S)-alcohol in 9.5% optical yield. A number of other similar reversals were observed. In ether solvent, an empirical relationship can be drawn between the configuration of the alcohol used for preparation of the reducing complex and the configuration of the enantiomeric product alcohol formed in excess. The relationship depends on the type of substrate used and is summarized in Table 8. 

An example of the solvent effect is also seen in the reaction of 3-acryloyl-l,3-oxazolidin-2-one (15b) which did not give sufficient asymmetric induction by the previous method.(18) The reaction of 15b with butadiene in 1,3,5-TMB gives the 3-cyclohexenecarboxylic acid derivative 22 in 77% optical purity. 

A study on the combined use of a chiral substrate obtained by alcoholysis of a 4-benzylidene-5(4//)-oxazolone with a chiral alcohol coupled with hydrogenation using a chiral catalyst has also been described. This work shows that the matching effect of double asymmetric induction in hydrogenation can be modulated by a solvent effect. 

When (PPh3)3PdCl2 is used as the catalyst precursor and optically active alcohols are used as the hydrogen donors, a small asymmetric induction occurs (see Table II) which could be due to a solvent effect (25). However, the large influence of the alcohol structure on re-gioselectivity suggests that the alcohol residue is present in (at least one of) the catalytic complexes. 

T. (2004) Noncovalent anchoring of asymmetric hydrogenation catalysts on a new mesoporous aluminosilicate application and solvent effects. Chem. Eur. ]., 10, 5829. 

Illustrated in Table III are the solvent effects. The carbonyl compound used is a-phenylpropionaldehyde and the optically active acid is D-camphorsulfonic acid. The figure reveals that when hydrolysis is carried out, less miscible solvents are more effective suggesting that interfacial reactions are effective for stereoselectivity of asymmetric transformations. 

The solvent effects show almost the same tendencies as when hydrolysis is effected by optically active acids. The absolute value of the optical rotation of the recovered a-phenylpropionaldehyde is much larger in these examples. This indicates that the use of an optically active amine is more effective for asymmetric transformation than the use of an optically active acid. In addition, this method has been proved very effective for each type of carbonyl compound previously mentioned (3). 

Coupling attempts conducted with (R,S)-214 led to lower enantioselection upon C-C bond formation, an observation that points to the significant role played by the relative configuration (R,R) of the binaphthyl and ethylenediamine units in promoting asymmetric induction. This complex was found to be the most efficient among several different structural variations. Solvent effects on this transformation were also studied (Table 35), with toluene and chlorobenzene giving the best results. Low solubility of the catalyst (diethyl ether and diiso-... 

Figure 44 Solvent effects on product distribution in the asymmetric ethylalu mi nation.

In asymmetric complexes of the type [(bpy)2RuCl(pi-pyz)Ru-(NH3)4L]4+, studies (94) revealed that there is a solvent donor-number (DN)-dependent contribution to the Frank-Condon barrier of approximately 0.006 eV/DN, which completely overwhelms the dielectric-continuum-theory-derived (l/Dop-l/Ds) solvent dependence typically observed in symmetrical dimers. In this case, variations in MMCT Eop with solvent give linear correlations when plotted against solvent dependent AEm, the difference in potential between the two ruthenium(III/II) couples, as shown in Fig. 10. The microscopic origin of this solvent effect was described by Curtis, Sullivan, and Meyer (122) in their study of solvatochromism in the charge transfer transitions of mononuclear Ru(II) and Ru(III) ammine complexes. The dependence... 

A striking solvent effect was observed in the reduction of a chiral a-keto amide, C6H5-CO-CO-NR2 (NR2 = (5)-proline methyl ester), with sodium tetrahy-dridoborate, leading to mandelic acid after hydrolysis [704]. When the a-keto amide was reduced in pure tetrahydrofuran or methanol, the resulting enantiomeric excess of (5)-mandelic acid produced was 36% and 4%, respectively. However, when a tetrahydrofuran/methanol (99 1 cL/L) solvent mixture was used, the enantiomeric excess increased to 64% ( ). In other solvent mixtures, a catalytic amount of a protic solvent (CH3OH or H2O) was found to be necessary for good asymmetric induction [704]. 

Tanaka, T. Kumanoto, T. Ishikawa, T. Solvent effects on stereoselectivity in 2,3-dimethyM- chromanone cyclization by quinine-catalyzed asymmetric intromolecular oxo-Michael addition. Tetrahedron-Asymmetry, 2000, 11 4633 637. 

As with many catalytic systems, additives can play an important role. During optimization of the asymmetric rearrangement of cyclopentenyl tertiary ethers to chiral cyclohexenyl tertiary ethers, Hoveyda found a strong solvent effect on the enantioselectivity of the reaction using (97b). Lewis basic (see Lewis Acids Bases) additives were used to modify the catalyst since (97i) is Lewis acidic and coordination could change the equilibration of the Mo-alkyhdene isomers and, thus, could alter the enantioselectivity. Coordination of Lewis base to the metal center might also change the fit of the chiral pocket. Addition of 10 equiv (vs. substrate) of THF substantially increased the enantiomeric excess of the product in the model transformation (Table 10). ft was surmised that... 

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