Synthesis and reactions of 4-aryloxyflavans

4α-Aryloxyflavans unsubstituted in ring A have been synthesised by the reaction of phenols with flavan-4β-ols in the presence of boron trifluoride in ether. If reaction times are prolonged beyond disappearance of the starting 4β-ols, thermodynamic control leads to 4-arylflavans and the yields of 4-aryloxyflavans are negligible. 4-Arylflavans are the sole products when the catalyst is toluene-p-sulphonic acid. Thermal decomposition of flavan-4β-yl phenol carbonate in the presence of phenols affords a synthesis of 4α-aryloxyflavans free from 4-arylflavans. Syntheses of 7-methoxy-4α-aryloxyflavans have not been successful, nor can 4-aryloxyflavan-3-ols be obtained from 3,4-diols by these methods. The 4-aryloxyflavans react rapidly with acids to yield 4-carbocations which can be trapped by a variety of nucleophiles yielding 4α-ols with water, 4α-alkoxyflavans with alcohols, 4α-arylflavans with phenols, and 4α-sulphides with thiols. 2,3-cis-Flav-3-ene epoxide reacts with phenols to give 2,3-cis-3,4-cis-4-aryloxyflavan-3-ols and with sodium salts of phenols to give 2,3-cis-3,4-trans-4-aryloxyflavan-3-ols. The 2,3-trans-epoxide similarly gives the 2,3-trans-4-aryloxyflavan-3-ols. A biflavonoid containing a 4-aryloxy link has been synthesised from the 2,3-trans-epoxide and 7-hydroxyflavan-4-one. A series of 2,3-trans-4′-methoxy-4-aryloxyflavan-3-ols has been synthesised from crude 2,3-trans-4′-methoxyflav-3-ene epoxide. The substitution of a methoxy group into position 7 of the flavonoid A-ring prevented the preparation of the epoxides, but the action of N-bromosuccinimide and sodium acetate in acetic anhydride and acetic acid on 7,4′-dimethoxyflav-3-ene gave 2,3-cis- and 2,3-trans-4-acetoxy-3-bromo-7,4′-dimethoxy-flavans, the latter of which was converted by the action of sodium salts of phenols into the expected 4-aryloxyflavan-3-ols. 5,7,3′,4′-Tetramethoxyflav-3-ene gave nuclear brominated products even with N-bromosuccinimide; thus the synthesis of 5,7,3′,4′-tetramethoxy-4-aryloxyflavan-3-ols has not been possible by this method