Isochroman-l-ones

Homofolic acid, 5,11-methenyl-tetrahydro-biological activity, 3, 327 Homofolic acid, tetrahydro-biological activity, 3, 327 Homoisoflavanones occurrence, 3, 722 thermoisomerization, 3, 722 thermolysis, 3, 728 Homolytic reactions heterocyclic compounds reviews, 1, 74 Homophthalic acid isocoumarins synthesis from, 3, 830 synthesis, 3, 830 Homophthalic anhydride isochroman-l-one synthesis from, 3, 860 20a-Homoporphyrin nomenclature, 1, 30 Homopterocarpin isolation, 4, 998 ( )- D- Homotestosterone synthesis, 1, 453 Homer-Emmons reaction chromene synthesis by, 3, 749 Hortiacine isolation, 3, 149 Hortiamine isolation, 3, 149... 

Isochroman-1-one, 4-morphilinocarbonyl-3-(p-nitrophenyl)-X-ray crystallography, 3, 624 Isochroman-l-one, 3-phenyl-synthesis, 3, 859... 

Isocoumarin, 3,4-dihydro- — see Isochroman-l-one Isocoumarin, 8-hydroxy-3-methyI-occurrence, 3, 677 Isocoumarin, 8-methoxy-3-methyI-reactions... 

As with five-membered heterocycles, phosphorus pentasulfide may replace a ring oxygen atom by sulfur, or it may effect replacement in an acyclic precursor and then bring about cyclization. Thus isochroman-l-one (99) is converted into thioisochroman-l-thione (100) under the same conditions a 3-arylisocoumarin( 101) produces a 3-ary 1-1-thioisocoumarin (102) only, with no replacement of the ring oxygen atom.122 A typical example of thiation, followed by cyclization, is the formation of 2-alkyl- or 2-aryl-3,l-benzo-thiazine-4-thiones (103) from /V-acylanthranilic acid esters (104) by treatment with phosphorus pentasulfide in boiling xylene.122... 

X-Ray diffraction shows that the p- nitrophenyl group is equatorial and the morpholinocar-bonyl moiety axial in the isochroman-l-one cis-3,4-dihydro-4-morpholinocarbonyl-3-p-nitrophenyl-l//- 2-benzopyran-l-one (175) <78JCS(P1)1351). The pyranone ring has a distorted twist conformation. 

The three isomers which are discussed in this section are isochroman-l-one or 3,4-dihydroisocoumarin (617), isochroman-3-one (618) and isochroman-4-one (619). None of them enjoy an extensive chemistry although a small number of natural products contain an isochromanone nucleus. 

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). 

Vinylbenzoic acids on cyclization yield either isochroman-l-ones or phthalides or a mixture of both types. The direction of ring closure is influenced by both steric and electronic factors (62AC(R)1070). The presence of an a-substituent in the vinylbenzoic acid (621 R = Ph) leads to phthalides, whereas only isochromanones result when no such substituent is present (621 R = H Scheme 238). Ring closure presumably involves attack by the carbonyl group at the centre of lowest electron density. Thus, 2-(l-methylethenyl)benzoic acid yields the phthalide, but 2-(2-methylpropenyl)benzoic acid gives the isochroman-l-one on halolac-tonization. 

Bromophenyl)ethanol undergoes a palladium-catalyzed carbonylation which results in the formation of isochroman-l-one (79H(12)92l). It is considered that the reaction involves formation of an aryl-palladium complex (624) through insertion of the zerovalent palladium complex (623) into the aryl halide. Insertion of carbon monoxide followed by reductive elimination of the metal as a complex species leads to the isochromanone (Scheme 242). 

When 2-bromobenzoic esters are treated with ir-(2-methoxyallyl)nickel bromide, the acetonyl group is introduced. Reductive cyclization of the methyl 2-acetonylbenzoates yielded isochroman-l-ones (77JOC1329). 

In a related manner, sodium 2-bromobenzoates have been converted into 2-allylbenzoic acids. A palladium-catalyzed cyclization involving nucleophilic attack of the carboxylate on the palladium-complexed alkene yielded an isocoumarin. However, in situ catalytic hydrogenation results in the formation of an isochroman-l-one. 

The direct oxidation of 2-(2-hydroxymethylphenyl)ethan-l-ols to isochroman-l-ones may proceed via the isochroman (61TL223). 

Treatment of isochroman-l-one derivatives 145 with lithio methoxyallene followed by quenching the reaction with water furnishes 3-benzoxocin-6-one derivatives 146 in good yields (Scheme 37) <2004SL481>. 

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