Synthesis of 2-(4-Aryl-1E,3E-butadienyl)benzoxazoles by the Horner-Wadsworth-Emmons Reaction

2-(4-Aryl-IE,3E-butadienyl)benzoxazole derivatives were synthesized by the Homer-Wadswonh-Emmons reaction of 2-phosphorylmethylbenzoxazoles with cinnamaldehydes in fair to good yield.In our antiasthmatic drug research project, we planned to synthesize a variety of 2-(4-aryl-IE,3E-I dienyl)benzoxazole derivatives.There are many kinds of 2-substituted benzoxazoles in natural products, 2 3 synthetic drugs and fluorescent whiteners.However.2-(4-aryl-1 E,3E-dienyl) derivatives have not been reported.Recently, synthesis of.2-styrylbenzoxazoleby means of the Homer-Wadsworth-Emmons (HWE) reaction of 4 2-phosphorylmethylbenzoxazole with benzaldehyde was reported.We also investigated this type of reaction for the synthesis of a variety of 2-(4-aryl-I E.3E-dienyl)oxazoles using cinnamaldehyde derivatives with 2-phosphorylmethylbenzoxaloles and 2-phosphoryln~ethyloxazolopyridine.2-Phosphorylmethylbenzoxaloles (4a-c) were prepared in three steps from o-aminophenols (la-c) by i) N-chloroacetylation with chloroacetyl chloride in the presence of NaHC03; ii) oxazole formation by treatment 5 with ethyl polyphosphate, and iii) the Arbuzov reaction with triethyl phosphite.For the preparation of 6 oxazolopyridylmethyl phosphonate (4d), the 2-chloromethyl precursor (3d) was obtained by 7 trichloroisocyanuric acid-mediated chlorination of 5, which was derived from i d by cyclization with triethyl orthoacetate.8 9Aldehydes (7a) and (7b) were prepared from ferulic acid (6a) and caffeic acid (6b) by esterification,