Аннотация:Tolterodine, an important urological drug, can be conveniently prepared starting from 1-[2-hydroxy-5-methyl)phenyl]-1-phenylethylene, accessible in high yield by alumina-promoted ortho alkenylation of p-cresol with phenylacetylene. The hydroformylation of this olefin, catalyzed by rhodium complexes both in homogeneous or in aqueous biphasic system, affords the desired linear aldehyde in about 80−90% yield. The reductive amination of this aldehyde, in the presence of HN(iPr)2 and Pd/C (5%) as the catalytic precursor at 4 atm H2 and 48 °C, produces directly tolterodine in more than 90% yield. Some experiments of enantioselective hydroformylation of 1-[2-hydroxy-5-methyl)phenyl]-1-phenylethylene catalyzed by Rh(CO)2acac/(S,R)-Binaphos and other enantiopure ferrocenyldiphosphines afforded only low yields of the expected chiral aldehyde; unfortunately, the achieved ee did not exceed 8%.
