Isoquinoline derivatives, Pictet-Gams

The extent of kinetically controlled formation of the carboxonium ions 31 depends on the nature of R1 and Yy. The possible existence of 31 allows formation of acylated enols 32 (Y = R3CO), which are analogous with w-acylaminostyrene derivatives. As is known, the latter compounds easily undergo an intramolecular acid-catalyzed cyclization to isoquinolines (the Pictet-Gams reaction) (80T1279). 

The Pictet-Gams method involves the cyclization of P-hydroxy- or P-methoxy- P-phenethylamides, and produces the isoquinoline derivative rather than the reduced form. A further extension of method is based on a metboxyetbyl amine. 

This method [Eq. (10)] was first used in 1930 by Kondo and Tanaka60 for the preparation of 4-hydroxy-5-methoxytetrahydroisoquinoline from j8-hydroxy-j8-(o-methoxyphenyl)ethylamine and methylal (mixed in aqueous HC1). Such ethanolamine derivatives are frequently used in the Bischler-Napieralski synthesis of isoquinolines61 as the Pictet-Gams modification. In this case, the reaction proceeds with dehydration to yield completely aromatic isoquinolines directly. Preparations of the ethanolamines have been reviewed.62... 

The Pictet-Gams reaction was used for the synthesis of difficult accessible isoquinoline derivatives as the tri-isoquinoline artificial receptor of resorcinol. ... 

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