The alkylation and ring-expansion of chromones by diazoalkanes; reluctance of oxygen to engage in sigmatropic shifts

Abstract

In general, chromones activated by electron-withdrawing groups at position 3 are alkylated (at position 2) by diazoalkanes in the same manner as the isomeric coumarins. For example, 6-methylchromone-3-carbonitrile (3a) is converted by diazoethane into 2-ethyl-6-methylchromone-3-carbonitrile (3c). 2-Diazopropane affords cyclopropane by-products as well, and a 3-formyl group usually suffers homologation to the appropriate ketone, as when 2-diazopropane converts 3-formyl-6-methylchromone into 2-isopropyl-6-methyl-3-(methylpropanoyl)chromone (8). In marked contrast to coumarin chemistry, there is no ring expansion into the 1-benzoxepin series.

Chromones activated at position 2 show diverse reactions. Although nitriles are usually considered to be unreactive towards diazoalkanes, 6-methylchromone-2-carbonitrile slowly gives a triazole; subsequent protropy and further alkylation results in the isolation of what is provisionally considered to be the 2-(1,2,3-triazol-4-yl)chromone (12a). 2-Formylchromone (13a) is converted by diazomethane into a mixture of 2-acetylchromone and the 2-oxiranylchromone (14) but it does undergo ring expansion by diazoethane and 2-diazopropane giving derivatives of 1-benzoxepin, e.g. (15). Ethyl chromone-2-carboxylate (17a) reacts very slowly but affords 1-benzoxepin derivatives as well as 3-alkylated chromones.

The ring-expansions are considered to occur by way of sigmatropic shifts in unstable pyrazolines as in diagram (20) for a 2-acylchromone adduct. There is no corresponding shift (and therefore no ring-expansion) for any 3-acylchromone adduct [diagram (6a)] whence it appears that sigmatropic shifts of oxygen are unexpectedly difficult.