A Synthesis of Mono- and Dimethoxy-1,2,3,4-tetrahydroisoquinolines via Pummerer Reaction : Effects of Methoxyl Groups on Intramolecular Cyclization

概要

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A synthesis of 1,2,3,4-tetrahydroisoquinolines (TIQs)(23) with one and two methoxyl groups at various positions of the benzene ring was achieved via the intramolecular cyclization of N-(aryl)methyl-2-(phenylsulfinyl)ethylamines (9) using the Pummerer reaction as a key step. The reaction was carried out by using trifluoroacetic anhydride (TFAA)(method A) of TFAA-BF_3・Et_2O (method B). The cyclization to 4-SPhTIQs (11) proceeded effectively when the reaction center at the benzene ring was electronically activated by a methoxyl group. In the reaction of the sulfoxide (9e) having two OMe groups at ortho- and para-positions a different cyclization reaction leading to a benzothiazepine (12) was observed, indicating that the high nucleophilicity of the benzene ring caused the unexpected reaction prior to the cyclization to 4-SPhTIQ (11e). The route starting from methoxylated benzaldehydes (5) was proved to provide an efficient and convenient method of TIQ synthesis which should be complementary to the well known Pictet-Spengler method.
公益社団法人日本薬学会の論文
1998-06-15