Synthesis of 2,3,5-trihydroxyphenylprop-1-ene and its 4-chloro-, 6-chloro-, and 4,6-dichloro- derivatives

Abstract

The synthesis of (E)-2,3,5-trihydroxyphenylprop-1-ene (2) and its 4-chloro-(3), 6-chloro-(4), and 4,6-dichloro- derivatives (5) is described. The routes involve the key intermediates, methyl 2,3,5-tribenzyloxybenzoate (15) and methyl 2,3,5-tribenzyloxy-4-chlorobenzoate (41) which were prepared from vanillin and 3,5-dimethoxytoluene (33), respectively. The benzoates (15) and (41) were treated with the anion from ethylphosphonic bis(dimethylamide)(6) to give the corresponding β-oxophosphonamides (17) and (42). These were reduced with sodium borohydride to the β-hydroxyphosphonamides (19) and (29), respectively. The benzyl protecting groups were removed by hydrogenolysis and subsequent treatment with acid gave the required phenylpropenes (2) and (3). The 6-chloro derivatives (4) and (5) were prepared via chlorination of the β-acetoxyphosphonam ides (27) and (44), respectively.