Efficient synthesis of optically active 4,5-dihydroxy-2,3,4,5-tetrahydro-1H-1-benzazepine derivatives utilizing lipase-catalyzed transesterification

As an efficient and enantioselective synthesis of the 4,5-dihydroxybenzazepine compounds, the syntheses of optically active 5-O-protected trans4,5-dihydroxybenzazepine derivatives were accomplished. The trans-7-chloro4-hydroxy-5-methoxymethoxy-1-(p-toluenesulfonyl)-2,3,4,5-tetrahydro-IH-1- benzazepine [(+/-)-4] was kinetically resolved by lipase-catalyzed transesterification. The optically active 4* was isomerized into the cis compound (6*) utilizing the Mitsunobu esterification followed by hydrolysis. The chiral compounds (4* and 6*) were converted to the 4,5-bismethoxymethoxy compounds (7*-10*), which were the intermediates for the compounds (2a, b and 3a, b).