Synthesis of Highly Condensed Aromatic Compounds by Using Isobenzofurans

Abstract

Isobenzofurans are 10π electron systems with a quinoid structure, which make them useful intermediate for natural/unnatural product syntheses. Among various possibilities, [4+2] cycloaddition with dienophiles is a reliable method for the rapid construction of polycyclic structure. In this context, a one─pot synthetic method of 1,3─diarylisobenzofurans has been developed via sequential nucleophilic addition to 2─formylbenzoate. 1,3─Bis (arylethynyl)─isobenzofurans has also been accessible by nucleophilic addition of alkynyllithium to benzocyclobutenone and subsequent oxidative ring cleavage of the four─membered ring.  Based on these new synthetic approaches to various isobenzofurans, successive [4+2] cycloadditions of isobenzofuran with benzynes and/or epoxynaphthalenes were developed, allowing us for rapid construction of various highly condensed aromatic compounds. Moreover, as a potentially versatile method for the rapid, selective assembly of functionalized polycycles, we also exploited the synthetic equivalent of bis─isobenzofuran, i.e. diepoxyanthracene, which enabled the iterative generation of isobenzofuran and subsequent functionalization and/or introduction of the fused ring by trapping with dienophile.  The essential point of these integrated syntheses is isolability of isobenzofuran, which would provide great opportunities to use this potentially attractive molecules under various reaction conditions.