A novel solid support for derivatization and subsequent N-alkylation of secondary amines: Preparation of N-alkylated 5- and 6-alkoxy-1,2,3,4-tetrahydroisoquinolines via Mitsunobu reaction

A hydroxymethylated polystyrene resin has been converted to its vinylsulfonylethyl ether (1) by DBU catalyzed addition of the hydroxy groups to divinyl sulfone. The support obtained was used to convert 5- and 6-(tetrahydropyran-2-yloxy)-1,2,3,4-tetrahydroisoquinolines to a set of N-alkylated tetrahydroisoquinolines bearing various 5- and 6-alkoxy substituents (5a-m). The synthesis involved attachment of the starting material to the support by Michael addition, acid-catalyzed removal of the tetrahydropyranyl protection, Mitsunobu etherification, quaternarization with alkyl amines, and release in solution with diisopropylethylamine. (C) 1997 Elsevier Science Ltd.