Simple synthesis of 5-substituted resorcinols: A revisited family of interesting bioactive molecules

Article abstract of DOI:10.1021/jo9610624

The reaction of 3,5-dimethoxybenzyl trimethylsilyl ether (3) with different aldehydes (n-PrCHO, n-C₁₁H₂₃CHO, MeCHO, PhCHO) in the presence of lithium powder and a catalytic amount of naphthalene (4 mol %) gave, after hydrolysis, the expected alcohols 4 in moderate yields. The dehydroxylation of these compounds through the corresponding mesylates 5 or directly from benzylic derivatives by catalytic hydrogenation, afforded compounds 6, which are finally demethylated to yield 5-alkyl-3,5-dihydroxyresorcinols, such as olivetol (7a), grevillol (7b), 1,3-dihydroxy-5-propylbenzene (7c), or dihydropinosilvine (7d). Dehydration of alcohol derivatives 4 followed by demethylation led to hydroxylated stilbene-type structures, such as pinosilvine (9d), resveratrol (9e), or piceatannol (9f), which in some cases can be hydrogenated to give saturated molecules such as combretastanin B-4 tetramethyl ether (6f) or chrysotobibenzyl (6g). Finally, when the naphthalene-catalyzed lithiation of compound 3 was performed in the presence of other electrophiles [Me₃SiCl, t-BuCHO, CH₃(CH₂)₄CHO, 4-Me₃SiOC₆H₄CHO, (CH₂)₅CO, PhN = C = O, PhN = CHPh], the expected reaction products 12 were isolated, after hydrolysis.