Kinetic resolution by enantioselective dihydroxylation of secondary allylic 4-methoxybenzoate esters using a mechanistically designed cinchona alkaloid catalyst

Article abstract of DOI:10.1021/ja00149a004

The OsO₄-cinchona alkaloid catalyzed asymmetric dihydroxylation process has been applied successfully to the kinetic resolution of 1-substituted allylic alcohols by the use of the 4-methoxybenzoyl derivatives in conjunction with the specifically designed DHQD-PYDZ-(S)-anthryl catalyst (5 · OsO₄). Thus, (±)-3-buten-2-yl 4-methoxybenzoate (4a) and (±)-1-phenyl-2-propen-1-yl 4-methoxybenzoate (4b) have been kinetically resolved with relative rate constants of 20 and 79, respectively. These values are among the best reported for the kinetic resolution of racemic compounds using non-enzymatic catalyst systems. The design of this resolution process was accomplished under mechanistic guidance using the transition state model proposed recently for the asymmetric dihydroxylation process. The specially selected ligand 5 possesses a deep U-shaped binding pocket with both the methoxyquinoline and the 1-anthryl walls projecting rearward of the pyridazine linker group at the floor. This catalyst not only recognizes the 4-methoxybenzoyl group of these substrates, which extends into the distant binding pocket of the catalyst, but also provides an open space adjacent to one of the allylic α-substituents of the substrate which allows for enantiomeric selection in the dihydroxylation. The magnitude of the kinetic resolution and the absolute stereopreference for the dihydroxylation reaction provide strong evidence for the guiding mechanistic model. The utility of this process is clearly demonstrated by the selective dihydroxylation of 1,4-pentadien-3-yl 4-methoxybenzoate (10) to give diol 11 in 70% isolated yield with >98% ee and >96% de.