The generation and synthetic utility of dianions derived from benzofurancarboxylic acids

Abstract

The dianionic species, lithium 2-lithiobenzofuran-3-carboxylate (5) and lithium 3-lithipbenzofuran-2-carboxylate (11b) can be readily generated from the parent acids by reaction with lithium di-isopropylamide in tetrahydrofuran at low temperatures. While compound (5) is a useful synthetic intermediate, which reacts efficiently with a number of electrophiles, (11b) instead undergoes rapid opening of the furan ring to give (2-hydroxyphenyl)propynoic acid (10a). By contrast, 5- and 7-methoxybenzofuran-2-carboxylic acids (13a) and (13c) give rise to the dianions (14a) and (14c) which are sufficiently stable at ⩽–90 °C to be trapped by aldehydes. The dianion (14b) derived from 6-methoxybenzofuran-2-carboxylic acid (13b), however, suffers rapid ring opening before it can be trapped, even at very low temperatures. A plausible explanation of these observations is given. Metallation of 3-methylbenzofuran-2-carboxylic acid (18) affords the dianion (20), which cannot undergo ring opening and which is a valuable intermediate for the synthesis of a range of 3-substituted benzofuran-2-carboxylic acids.