Stereoselective synthesis of morphine fragments trans- and cis-octahydro-1H-benzo[4,5]furo[3,2-e]isoquinolines

A stereoselective synthesis of the ACNO partial structures of morphine has been developed. Palladium-catalyzed cyclization of carbamate provided the tetracyclic (ACNO) 3-ethoxycarbonyl-9-methoxy-2,3,5,6,7,7a-hexahydro-1H-benzofuro[3,2-e]isoquinoline (); while treatment of 5-(2-bromo-6-methoxyphenoxy)-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline () under the same reaction condition gave 8a-(2-hydroxy-3-methoxyphenyl)-1,2,3,4,6,7,8,8a-octahydroisoquinoline () via an unusual Claisen rearrangement. 9-Methoxy-3-methyl-2,3,5,6,7,7a-hexahydro-1H-benzofuro[3,2-e]isoquinoline () was successfully transformed to trans-octahydroisoquinoline and cis-octahydroisoquinoline via catalytical hydrogenation over PtO2 and chemical reduction with acidic NaBH4, respectively.