Synthesis and Reactions of Isoquinolones

Aromatic isoquinolones can be obtained by the thermal rearrangement of isoquinoline iV-oxides thus it was possible to derive the isoquinoline 3 from the iV-oxide 2. Compound 3 could be further functionalized through bromina-tion and subsequent treatment with a mixture of cuprous cyanide and sodium cyanide.  

A new synthesis of isoquinolones originates with homophthalic acid, and is described in the following sequence  

This sequence was adapted to provide the protoberberine lactam 4 the starting material was obtained from reduction of the imide derived from homoveratrylamine and homophthalic acid. 

It is known that tetrahydrobenzylisoquinolines can be cleaved to isoquinolones using potassium permanganate. A method has now been developed for the oxidation of isoquinolinium salts. Taking papaverine methiodide as an example, this salt is first treated with aqueous alkali to supply the enamine 5. Treatment of a benzene solution of the enamine with oxygen in the presence of cuprous chloride provides the isoquinolone 6 in 0% yield. (For the oxidation of bisbenzylisoquinolines to isoquinolones, see Secs. 5.4 and 6.1.) 

The introduction of a 3,4-double bond in an isoquinolone is often difficult. In the synthesis of thalactamine, this dehydrogenation was performed using palladium on carbon.  

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