KINETIC RESOLUTION BY ENANTIOSELECTIVE DIHYDROXYLATION OF SECONDARY ALLYLIC 4-METHOXYBENZOATE ESTERS USING A MECHANISTICALLY DESIGNED CINCHONA ALKALOID CATALYST

The OsO4-cinchona alkaloid catalyzed asymmetric dihydroxylation proces s has been applied successfully to the kinetic resolution of 1-substit uted allylic alcohols by the use of the 4-methoxybenzoyl derivatives i n conjunction with the specifically designed DHQD-PYDZ(S)-anthryl cata lyst (5 . OsO4). Thus, (+/-)-3-buten-2-yl 4-methoxybenzoate (4a) and ( +/-)-1-phenyl-2-propen-1-yl 4-methoxybenzoate (4b) have been kinetical ly resolved with relative rate constants of 20 and 79, respectively. T hese 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 us ing the transition state model proposed recently for the asymmetric di hydroxylation process. The specially selected ligand 5 possesses a dee p U-shaped binding pocket with both the methoxyquinoline and the 1-ant hryl walls projecting rearward of the pyridazine linker group at the f loor. 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 ally lic alpha-substituents of the substrate which allows for enantiomeric selection in the dihydroxylation. The magnitude of the kinetic resolut ion and the absolute stereopreference for the dihydroxylation reaction provide strong evidence for the guiding mechanistic model. The utilit y of this process is clearly demonstrated by the selective dihydroxyla tion of 1,4-pentadien-3-yl 4-methoxybenzoate (10) to give diol 11 in 7 0% isolated yield with >98% ee and >96% de.