Hirozumi Inoue

Highly enantioselective reduction of meso-cyclic-1,2-dicarboximides. Asymmetric synthesis of bicyclic 2-pyrrolidinone and its 5-hydroxy congener

Bicyclic 5-hydroxy-2-pyrrolidinones (2a - f) were synthesized with high enantioselectivity by the reduction of meso-cyclic-1,2-dicarboximides (1a - f) with lithium aluminum hydride (LiAlH 4 )-methanol (MeOH)-1,1-bi-2-naphthol complex (BINAL-H). Treatment of 2a - f with triethylsilane (Et 3 SiH) and trifluoroacetic acid(CF 3 CO 2 H) gave optically active 2-pyrrolidinones (3a - f) in quantitative yields. For the absolute configuration correlation, 2a - d were converted into known lactones (4a - d)

Synthesis and pharmacology of 5-noralkyl-9.beta.-methyl-6,7-benzomorphans and stereochemistry of some intermediates

2,9beta-Dimethyl-2-hydroxy-6,7-benzomorphan (18) has been synthesized from m-methoxyphenylacetone (6a) or m-methoxyphenylacetonitrile (1) via bromo-alpha-tetralone (10). Isomeric bromo-alpha-tetralone 9, instead of undergoing cyclization to a 6,7-benzomorphan, gave aromatization product 12. The structures and stereochemical assignments of 9, 10 (and thus 7 and 8), and 18 follow from analogy and from NMR data of 9, 10, 17, and 18. Compound 18 and the deoxy analog 16 are as potent as morphine and codeine, respectively, as analgetics (mice) and are without physical dependence capacity (monkeys).