Structurally Related Ligands

The FEP method has shown good accuracy when used to determine the relative binding affinity for two structurally-related ligands. Unfortunately, the newly designed analogues requested by medicinal chemists frequently represent large structural changes from the lead compound and therefore are not well suited for the FEP method. 

Tanner et al. (58) investigated the asymmetric aziridination of styrene using bis(aziridines) such as 85. Low induction is observed with these ligands, Eq. 64. A significant electronic effect was noted with the p-fluoro-phenyl substituted bis(az-iridine) 85c (59). A binaphthyl-derived diamine was used as a ligand for the copper-catalyzed aziridination of dihydronaphthalene (81). The product was formed in 21% ee and 40% yield, Eq. 65. Other structurally related ligands proved to be less selective in this reaction. 

Based on all evidence above, I propose the mode of action of OBPs follows the model depicted in Figure 15.8. OBPs participate in the selective transport of pheromones and other semiochemicals to their olfactory receptors. By selectivity, I do not mean that OBPs are the only filter of the olfactory system. In other words, I believe that OBPs may bind, solubilize, and transport structurally related ligands, but not compounds with unrelated chemical structures. This view is supported by the native gel-binding assay with BmPBP (Wojtasek and Leal, 1999) that showed binding to bombykol, but not to lactones, such as (R)- and... 

FIG. 12. Synthesis of (S)-2-phenylbutyldiphenylphosphine. Catalysts prepared from this ligand, and structurally related ligands, typically give products of low optical purity (31). 

Significant data are available only on the a- and /S-diketones and structurally related ligands.283 A single tris-chelate cationic species of dimethylphthalate appears to be the sole representative of the y-diketone type. 

The entropies of formation of the 1 1 bivalent metal complexes of the structurally related ligands, Formulas IX-XIII, reported by Martell (10) show a linear correlation with the square of the reciprocal of the effective ionic radius of the metal ions, r , in Equation 8, and with the number of negative carboxylate groups of the ligand that combine with the metal ion. 

Both developments opened up a new era of asymmetric hydroformylation. The results are promising and research is now focused on the synthesis of structurally related ligands. Other ligands, such as the P-N ligand 10, are also showing very high selectivities. Faraone and co-workers, in the hydroformylation of vinyl-naphthalene, reported the exclusive formation of the branched aldehyde while a rhodium/10 catalyst was used (conversion 100%) [84], The enantiomeric excess obtained was 78 % for the / -enantiomer. With methylacrylates an ee of 92 % was observed. For further informations see Sections 2.9 and 3.3.1. 

A different ligand type was presented with ACTC 63 [46]. From the four structurally related ligands, complex 65 performed best yielding the (S)-configurated alcohol with 70% ee from the reaction of benzaldehyde with diethyl zinc. In this... 

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