Reductive Ring-Opening of Phthalan and Isochroman: Application to the Stereoselective Synthesis of Tetrahydroisoquinolines and Tetrahydrobenzazepines

The reaction of the dianionic intermediates 2a,b resulting from the lithiation of phthalan (1a) and isochroman (1b) with chiral N-tert-butylsulfinyl aldimines 9 in the presence of ZnMe2 gave, after hydrolysis, N-tert-butylsulfinyl amino alcohols 10 and 13, respectively, with high diastereoselectivity. Successive treatment of compounds 10 and 13 with hydrogen chloride in methanol, thionyl chloride in chloroform and sodium hydroxide led to the formation of tetrahydroisoquinolines 19 and tetrahydrobenzazepines 20. Depending on the structure of the starting chiral imine 9, benzoindolizidine 21, benzoquinolizidine 22 and benzopyrroloazepine 23 are also accessible through this methodology.