Isochromanones synthesis

Carbonylation. The development of a 3-isochromanone synthesis using the carbonylation method is the extension of some previous work. More unusual is the introduction of a ketone side chain to the piperazine system. ... 

While this method was originally reported in 2002, the true applicability in complex target synthesis has been limited by apparent difficulties resulting from cleavage of the amide residue and the lability of the newly generated benzylic alcohol. Therefore, it was anticipated that considerable effort would have to be invested in applying this approach for isochromanone synthesis. 

Benzoxepin-4-carbaldehyde, dihydro-from chromones, 3, 713 Benzoxepin-4(3H)-one from isochromanone, 3, 726 [l]Benzoxepino[3,4-d]selenazoles synthesis, 6, 345 Benzoxepins... 

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... 

Oxidation of dihydroisocoumarins is conveniently achieved through bromination with NBS followed by dehydrohalogenation with triethylamine (62JOC4337, 71T6171). Since the oxidation of isochromans to isochromanones proceeds readily using chromium trioxide, this method effectively constitutes a synthesis of isocoumarins from isochromans. 

The acid has been formed by the reduction of 2-carboxyphenylacetaldehyde, itself available from indene by ozonolysis (57JA3165). This is one of the most convenient methods of synthesis of isochroman-l-one, which is obtained in a 70% overall yield from indene (Scheme 236), and has been used in the synthesis of isochromanones with specific deuterium labels <8ljcs(Pl)l685). 

A convenient synthesis of isochroman-3-one is based on the reaction of phenylacetic acids with formalin and concentrated hydrochloric acid (760S(55)45>. An indication of the value of the isochromanone as a synthetic intermediate is given in this procedure. 

Acylation of the keto acid (637) leads to the isobenzopyrylium salt (638) (77CHE1183). However, the isobenzopyrylium salt (639), a potential intermediate for the synthesis of analogues of berberine alkaloids, results from the formylation of the substituted ketone or the isochromanone (640) using dichloromethyl butyl ether (Scheme 251) (81CHE221). A second product, the 5-oxoniachrysene (641), is formed and this compound may also be obtained by reaction of the isobenzopyrylium salt with phosphorus pentachloride and then with triethylamine. The intermediacy of a cyclic vinyl ether is proposed. 

Another interesting synthesis of the isochromanone ring system is through metallation of an aromatic methyl group which is ortho to a hydroxymethyl group in the aromatic ring 2 . 

Similarly isochromanones have been used for the synthesis of selenium analo-... 

Iron(1 +), dicarbonylethene(i]5-cyclopentadieny )- addition of carbon nucleophiles, 44 —, tricarbonyl(T -cyclohexadienyl)- addition of carbon nucleophiles, 44 Isobutyryl chloride, ot-acetoxy-, 160 3-Isochromanone, 1,4-dihydro-, 80 Isocyanates blocking of OH with, 301 Mocking of SH with, 229, 238 synthesis, 143, 301, 331 Isocyanides trapping of diallylnickel, 41 Isodrin pr., 192... 

Pyrolysis of isochromanones in the gas phase at 500 °C, with resultant loss of carbon dioxide, has afforded a new synthesis of 4,5-dimethoxy-, 4,5-methylenedioxy-, and 4-methoxy-benzocyclobutene. Photosolvolysis of 2-(3,5-dimethoxyphenyl)ethyl methanesulphonate in 50% aqueous methanol gave inter alia small amounts of 3,5-dimethoxybenzocyclobutene. 

Bis(phosphonium salts) of the type shown in Fig. 9 were identified as by-products in catalytic systems involving o-xylylene-a,a -dihalides, carbon monoxide and Pd-triphenylphosphine complexes, applied in the synthesis of 3-isochromanones. ... 

Stereoselective Synthesis of Isochromanones with and Without Activated Spin Intermediates Total Synthesis of Ajudazol B... 

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