Synthetic studies on isoquinoline alkaloids. II. Selective conversion of 3,9,10-substituted tetrahydroprotoberberines into 3,9,10-substituted 5,6,7,8,13,14-hexahydrodibenz(c,g)azecines.

Abstract

An efficient method for highly selective conversion of 3, 9, 10-trisubstituted tetrahydroprotoberberines into the corresponding 3, 9, 10-substituted 5, 6, 7, 8, 13, 14-hexahydrodibenz (c, g) azecines was established as exemplified by high yield conversions of 13 into 15 and 1g into 29. The method involves Emde reduction (Birch modification) of the methiodide 14 or 28, in which the C9-phenolic function is specifically protected by the benzyl group enabling selective reductive fission at the C13a-N bond. By application of this method combined with the method newly developed in our laboratory for synthesis of 9, 10-substituted tetrahydroprotoberberines, a straight-forward and sophisticated total synthesis of 9, 10-dimethoxy-3-hydroxy-7-methyl-5, 6, 7, 8, 13, 14-hexahydrodibenz (c, g)-azecine (2a) was achieved as illustrated in Chart 8. The cyclopropylmethyl group was newly introduced as a very useful protecting group for a phenolic function.