Pictet-Gams isoquinoline synthesis modifications

Alternatively, a P-methoxy-P-phenylethylamine can be used to circumvent the oxidation step after the conventional Bischler-Naperialski cyclization. Here, when treated with the phosphorus reagent the amide (R = OMe) undergoes both cyclization and the elimination of methanol to give the isoquinoline (R = H) directly. This is known as the Pictet-Gams modification of the Bischler-Napieralski synthesis. 

The Pictet-Gams modification of the Bischler-Napieralski synthesis has also been reviewed (5loR(6)74, 81HC(38-l)l6i). As shown in equation (32), the additional unsaturation is achieved by elimination of ROH before the cyclization. The commonest examples use j8-hydroxy or /3-methoxy substituents on the phenethylamide. Papaverine (107) is an example of an isoquinoline obtained from both precursors (09CB2943, 27AP(265)l). The precursors can be made from 5-aryloxazolines by reaction with an acid chloride and... 

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... 

Nowadays, several modifications of the Pictet-Gams reaction exist in the literature, constituting the reaction as the method of choice for the synthesis of isoquinoline frameworks when acid labile substituents are not present in the molecule. Modifications include the use of cinnamic esters, instead of 2-phenyl-2-hydroxy ethanamines, as starting materials... 

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