Hydrophobically-directed selective reductions and oxidations

The hydrophobic effect was exploited to attain selectivity in atom-transfer reactions where reactive functionalities were located in both hydrophobic and non-hydrophobic environments. In hydride-transfer reactions, various hydrophobic borohydride reagents were employed in an aqueous medium to effect the selective reduction of the hydrophobic ketone in competition reactions between various hydrophobic ketones and a non-hydrophobic methyl ketone. In these reactions a trend was established where greater hydrophobicity in the reagent and substrate correlated to greater selectivity. The largest selectivities were obtained when LiC6F5BH3 was employed as the reducing agent. Salt effects imply that hydrophobic packing in the transition state of the reaction is the source of the observed rate increase for reduction of the hydrophobic substrates. In all cases the hydrophobic direction could be suppressed by the addition of an organic co-solvent, which further implicates the hydrophobic effect as the source of the selectivity. The propensity of the hydrophobic unit and the ketone to assume a coplanar, conjugated conformation was shown to relate directly to the observed selectivities. In the competition reaction of a 2-naphthyl ketone and a methyl ketone, a 40-fold relative rate acceleration for the reduction of the 2-naphthyl ketone was observed when LiC6F5BH3 was employed instead of LiBH4 and the reaction medium was changed from organic to aqueous.; In the hydrophobically-directed oxidation studies, the selective epoxidation of cinnamates versus crotonate was used to detect the hydrophobic binding of the cinnamates in the transition state of epoxidation using hydrophobic oxidizing agents in water. When peracids were employed as the oxidants, no hydrophobic enhancement of selectivity was observed. This is consistent with the calculated geometries of epoxidation, which predict that the hydrophobic units of the olefin and peracid cannot pack in the transition state. When oxaziridinium salts with tetrahydroisoquinoline backbones were employed as the oxidants, a high selectivity for the epoxidation of the cinnamates was observed in water. This selectivity could be partially suppressed by the addition of isopropyl alcohol. Furthermore, the oxaziridinium salts could be generated in situ from catalytic amounts of the associated iminium salts using Oxone as the stoichiometric co-oxidant. When non-hydrophobic dimethyldioxirane was employed as the oxidant, a significant reduction of selectivity was observed, which again implicates the hydrophobic effect as the main source of the selectivity. In the competition reaction between a 2-naphthyl substituted cinnamate and crotonate, a 250-fold change in selectivity was observed when the epoxidizing agent was changed from dimethyldioxirane to an oxaziridinium salt in a water solution. In free energy terms, this selectivity change is greater than any observed in hydrophobic reductions.