Flavan derivatives. XVII. Epimerization of the benzylic 4-hydroxyl group in flavan-3,4-diols and the formation of 4-alkyl ethers by solvolysis

Abstract

Epimerization and solvolysis of the benzylic 4-hydroxyl group is shown to be a general property of flavan-3,4-diols, and the diols give 4- ethoxyflavan-3-ols with ethanolic hydrochloric acid (1%). The diols are first converted into epimeric mixtures of 3,4-cis- and 3,4-trans-diols and in aqueous media cis-cis-flavan-3,4-diols yield mainly 2,3-cis-3,4- trans-diols. These 2,3-cis-3,4-diols undergo solvolysis to yield 2,3- cis-3,4-trans-4-ethoxyflavan-3-ols in which the 3,4-trans- stereochemistry is controlled by participation of the neighbouring 3ax- hydroxyl group. 2,3-trans-Flavan-3,4-diols give mixtures of trans- trans-diols and 2,3-trans-3,4-cis-diols and solvolysis first yields 2.3-trans-3,4-cis-4-ethoxyflavan-3-ols and then mixtures of the 3,4- cis- and 3,4-trans-ethers; the final proportion of these two ethers is controlled by thermodynamic factors. Solvolysis under mild conditions gives minor products considered to be 3-oxoflavans (or their enols) because of their immediate conversion into antho-cyanidins by cold acids in the presence of air, and from the formation of an enol-ether on prolonged solvolysis under more vigorous conditions. The relevance of these observations to the mechanism of formation of anthocyanidins from flavan-3,4-diols is discussed. Other by-products of solvolysis reactions include a dimeric cyclic ether (dioxan derivative) of 2,3- trans-3,4-cis-7,8,4?-trimethoxyflavan-3,4-diol. The structure and stereochemistry of solvolysis products were established by N.M.R. data; the 4-ethoxyl group in the ethers generally gave rise to an ABX₃ multiplet.