CATALYTIC ASYMMETRIC CONSTRUCTION OF MORPHOLINES AND PIPERAZINES BY PALLADIUM-CATALYZED TANDEM ALLYLIC SUBSTITUTION-REACTIONS

Reaction of 1,4-diacetoxy-cis-2-butene (1a) with 2-(benzylamino)ethanol (2a) was catalyzed by a palladium complex (5 mol %) coordinated with (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl to give optically active (R)-4-benzyl-2-vinylmorpholine (3a) of up to 65% ee. Optically active 1,4-bis(p-tolylsulfonyl)-2-vinylpiperazine (7a) (60% ee) was also obtained from 1,4-dicarbomethoxy-2-butene (1b) and 1,2-bis[(p-tolylsulfonyl)amino]ethane (6a) in a similar manner. This cyclization proceeds through a tandem allylic substitution via pi-allylpalladium intermediates. The palladium-catalyzed reaction with 2-amino-1,3-propanediols 17 gave 2-vinyl-5-(hydroxymethyl)morpholines of up to 73 % ee.