Aryl-stacking effects

Among the uses of other amino acids, L-tryptophan gives high ees and des in direct aldols of cyclic ketones and benzaldehydes in water 118 hydrophobic and aryl-stacking effects have been considered in explaining the selectivities. 

Aryl stacking effects in the transition state appear to play a role in the enantioselective addition of dimethylzmc to benzaldehyde when an A-benzylmandelamide-Ti(IV) complex is used as catalyst.235... 

Experiments with quinoxaline complex 23 and phenazine complex 24 established that additional binding interactions were available in the form of aryl-aryl stacking between aromatic subunits in the components. In the case of quinoxaline this accounts for about 1.6 kcal or a factor of 15 in Ka. In 24, these attractive forces are partially offset by steric effects introduced by the remote ring as shown. 

Tridentate chiral Schiff bases derived from (- -)-Q -pinene (123) catalyse enantioselective addition of diethylzinc to aryl aldehydes. Steric, aryl stacking, and electronic effects are significant in the transition state, the latter being probed by a Hammett plot of ee versus for a series of benzaldehydes. Complexes of the Schiff base (123) with titanium(IV) catalyse enantioselective cyanation. ... 

Figure 5 Examples of self-complementary molecules that yield dimeric assemblies (a) Cartoon representation of velcrand dimers that assemble through CH-pi, aryl-aryl stacking, and entropic effects (b) Rebek s softbaU dimCTs assembled through H-bonding (c) Nolte s molecular clips assanble into dimers through aryl-stacking and entropic effects. ...

These catalysts are believed to function through an acyclic TS. In addition to the normal steric effects of the open TS, the facial selectivity is probably influenced by tt stacking with the aryl ring and possibly hydrogen bonding by the formyl hydrogen.152... 

A corollary to the above is to remove or modify aryl moieties in the target molecule. This may have the effect of reducing clog P and potentially disrupting re-stacking with the channel. 

We have already seen (Section 3.12.6) how strong -stacking interactions occur with the aryl corands 3.116 and 3.117 and the herbicide paraquat (3.113) (e.g. 3.116 + 3.113, Ku = 730 M-1 in Me2CO), resulting in solid-state and solution incorporation of the electron-deficient guest within the corand ring. This inclusion of paraquat within the macrocycle is effectively the formation of a [2] pseudorotaxane, and this... 

In summary, the evidence for classical hydrophobic effects in supramolecular complexes is often missing. Careful investigations with model compounds, where one can measure the balance of conformations, show that stacking interactions, e.g., with more hydrophilic heterocyclic aromatic moieties, are stronger than with more hydrophobic arenes. " This (as well as the small effects of alkyl in comparison to aryl ligands in associations with, for instance, porphyrins) evidence supports the finding... 

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