Isochromane derivatives, formation

Carboxybenzyl aryl ketones are formed together with the isocoumarin when homophthalic anhydride (isochroman-l,3-dione) is used to acylate aromatic molecules under Friedel-Crafts conditions (51JOC1064) and the 7-methoxy derivative behaves in a similar fashion (66JIC615). Some care in the choice of Lewis acid is necessary in view of the formation of the tropone derivative (504) in the acylation of hydroquinone (Scheme 181) (55JCS2244). 

Formation of the isochroman system is considered to trigger the synthesis of the dibenzopyran (17, X = H2) by the acid catalysed cyclisation of c/s-enediynes (16, X = H2). In a similar manner, the carboxyl function in (16, X = O) promotes cylisation to a dihydropyranone derivative which is followed by a Myers cycloaromatisation to the dibenzopyranone (17, X = O) (95TL9165). 

Vinylnorcaradiene derivatives 1175 undergo a photochemical reaction resulting in the regioselective cleavage of one of the cyclopropyl a-bonds and the formation of isochroman-3-ones (Equation 457) <1997CC1973>. 

Aryl-l,3-dioxolanes undergo a TiCU-promoted Pictet-Spengler rearrangement to give 4-hydroxyisochromans. Bulky substituents at C-2 and C-4 of the dioxolane moiety result in formation of the cw-l,3-disubstituted isochroman while the 2,4-dimethyl derivative affords mainly the tran -diastereomer <04TL411>. 

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