L -isoquinolones

In a related type of reaction, the styryl isocyanates, readily available by Curtius rearrangement of cinnamoyl azides, undergo thermal cyclization to l-isoquinolones in good yield (equation 34) the reaction can also be carrried out using Friedel-Crafts catalysts. 2,3-Dihydro-4( 1//)- isoquinolones are obtained by Dieckmann cyclization of N- (o- carbalkoxy-benzyl)glycine ester derivatives (equation 35). The same reaction has been used for the synthesis of a range of non-aromatic heterocycles (equations 36 and 37). 

The transformation (190 — 191) exemplifies the use of transition metal reagents the reaction probably involves aminopalladation of the C = C bond (77JOC1329). 2,3-Dihydro-4(l//)isoquinolones are obtained by Dieckmann cyclization of 7V-(o-alkoxycarbonylbenzyl)glycine ester derivatives (192 - 193). 

Oxidation of iV-aminopyridinium, N-aminoquinolinium, and N-amino-isoquinolinium bromides with lead tetraacetate in acetic acid affords 1-acetamido-2-pyridone (139), l-acetamido-2-quinolone (140), and 2-ace-tamido-l-isoquinolone (141), respectively.42 A similar oxidation is reported to occur with 2-aminoimidazopyridinium salts.258 There is good evidence that the oxidation implicates the bromide ion.42... 

As for quinolines, isoquinoline derivatives can be prepared by ring transformation of other heterocycles. For instance, oxazole-4-carboxylic ester 74, obtained from phthalic anhydride and isocyanoacetic ester, is converted into the l-isoquinolone-3-carboxylic ester 75 in an acidic medium, probably by hydrolysis to the enaminocarboxylic acid 76 followed by cyclization. 

The free A-aryl-l-isoquinolone molecule can be obtained by hydrolysis of the carbonylated nickel complex shown in Equation (6). 

The first example of a naturally occurring isoquinolone was doryanine isolated by Gharbo.et al. (1965) from the Australian sassafras tree Doryphora sassafras, and workers of the same laboratory later isolated doryphomine from the same species (Chen et al. 1974). The authors assumed that isoquinolones may be formed in the plant by oxidation of benzylisoquinolines or similar alkaloids, and this view now appears to be generally accepted (Krane and Shamma 1982). Indirect support for this hypothesis may be the presence of the bisbenzyhsoquinoline alkaloid thali-carpine and its two oxidation products hemandaline and N-methyl-6,7-dimethoxy-l-isoquinolone in Hernandia ovigera (Cava and Bessho 1966). 

The parent, unsubstituted isochromanone has been caused to react with a variety of aromatic amines to prepare Ar-substituted 1,4-dihydro-3(2.ff)-isoquinolones,4 and with amines to give amides.5 The 6,7-methylenedioxy-3-isochromanone was an intermediate in the synthesis of protopine and its allied alkaloids,6 and for the synthesis of the berberine ring system.7 The 6-methoxy analog was prepared as a potential intermediate in a camptothecin synthesis8 and 8-methoxy-4,5,6,7-tetramethyl-3-isochromanonc was an intermediate in the synthesis of sclerin.9 The compound herein described was the basis of a facile synthesis of ( l )-xylopmins,10 and its reaction with hydrazine has been reported.11... 

Esters of 2-(2-methylphenyl)hydrazinecarboxylic acids were metaUated with excess LDA, and the resulting polyanion intermediates were condensed with aromatic esters followed by acid cyclization to give 3-substituted l(2f/)-isoquinolones 76 <96SC(26)1763>. 

A new synthetic route to 2-alkyl-4-aryl-l(2ff)-isoquinolones 77 involves the base promoted cyclization of phosphorylated o-aroylbenzamides <96T(52)4433>. 

Table 3 4x4 ligand matrix of aminopyridine (4a-d)/isoquinolone (5a-d) derived self-assembled bidentate ligands in the [Rh]-catalyzed hydroformylation of l-octenea... 

Quinoline and isoquinoline with MP in ether yield benzoindolizines,382 on exact analogy with the pyridine series. Isoquinoline with but-l-yn-3-one in acetonitrile give the isoquinolone 330, doubtless due to the presence of traces of water, but in ether an uncommon reaction giving an oxazine (331) is observed.299 In the presence of proton donors, isoquinoline behaves like pyridine with MP241,382 or but-l-yn-3-one,299 but the anion only reacts at position 1, giving products such as 332. The anion adds at position 4 in a few similar reactions involving quinolines.241,299... 

Details of the sequence of steps in the thionyl chloride-mediated transformation of 4-carboxy-3,4-dihydro-3-phenyl-l(2//)-isoquinolines into indeno[l,2-c]isoquinolones have been elucidated62 and it is confirmed that the dehydrogenation precedes the electrophilic cyclization [of (56)]. 

C Chemical Shifts of 1,2,3,4-Tetrahydroisoquinolines Substituted at C-l and of Some Isoquinolones... 

Several isoquinolones have also been examined (17). The carbonyl group at C-l in the isoquinolones, noroxohydrastinine (17) (7), corydaldine (18)... 

The 4-keto-l,2,3,4-tetrahydroisoquinolines are more systematically called 2,3-dihydro-4(l.ff J-isoquinolones, but the keto nomenclature would seem to be more descriptive of their properties. 

R = H). Bromination gave the 4-bromo-derivative which afforded (16 R = CN) and (16 R = CHO) by successive cyanization and Raney nickel reduction/ The reported synthesis of the isoquinolone alkaloid thalactamine from 2,3.4-trimethoxyphenethylamine is unexceptional but an alternative synthesis involving bromination of 6,7-dimethoxy-2-methyl-l(2//)-isoquinolone followed by methan-nolysis in methanolic sodium methoxide is somewhat surprising/ A number of new methods for preparing AT-substituted l(2//)-isoquinolones include reaction of homophthalic acids with Vilsmeier reagentand borohydride reduction of homophthalimides. The effect of various substituents on the fluorescence of such isoquinolones has been studied. 

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