A Synthesis of Some Trimethoxylated 1,2,3,4-Tetrahydroisoquinoline Alkaloids via Pummerer Reaction of N-Trimethoxybenzyl-N-[2-(phenyl- sulfinyl)ethyl]formamides

Pummerer reaction of N-trimethoxybenzyl-N-[Z-(phenylsulfinyl)ethyI]formamides (7) gave N-formyl-1,2,3,4-tetrahydro-4-phenylsulfanylisoquinolines (9) which were converted into trimethoxylated 1,2,3,4tetrahydroisoquinoline alkaloids in the family of Cactaceae, formylanhalinine (loa), nortehaunine (lZa), anhalinine (12b), and tehaunine (13a).We modified the Takano's 1,2,3,4-tetrahydroisoquinoline (TIQ) synthesis' which utilized Pummerer reaction and established the method as a general TIQ synthesis.In the investigations, we demonstrated that the cyclization of N-(ary1)methyl-N-2-[(phenylsulfinyl)ethydes by the Pummerer reaction was affected by the position of methoxy group at the aryl ring.For example, the reaction of the sulfoxide (la)with 2,3-dimethoxy groups gave the TIQ (2a) in an excellent yield.Id However, the reaction of the sulfoxide (lb) having 3,5-dimethoxy groups, in addition to the normal cyclization to the TIQ (2b), caused a C-S bond formation to give a benzothiazepine (3) as a majorOn the other hand, the sulfoxide (lc) with 2,4-dimethoxy groups did not undergo either cyclization and suffered an extensive decomp~sition.'~The findings indicated that the higher nucleophilicity at the ring-closing site prevented the TIQ formation.