New Syntheses of Diaryl Ethers, Tyrosinols, B-Hydroxytyrosinols, L,L-Isodityrosinol and L,L-Isodityrosine-Derived Agents via the Diels-Alder Reaction

Xianqi Feng
Syntheses of diaryl ethers were approached by use of a Diels-Alder reaction employing a new type of diene attached with an aryloxy group. Thus, 2-methyl-3-phenoxybutadiene (90b ), 2- methoxy-3-phenoxybutadiene (92b) and (4S)-3-(t- butyloxycarbony1)-2 ,2-dimethyl-4-( 4-(3-methoxy-1,3 -butadienyl-2- oxy )phenylmethyl]oxazolidine (93b) were synthesized in ~65% yields by methylenation of the carbonyl function in the corresponding 2- substituted acrylate aryl ester using Tebbe's reagent. The 1,3-
more » ... [(trimethylsilyl)oxy ]-2-phenoxybutadiene (105) was made from 1-phenoxy-2-propanone (101) by a sequence of formylation and enolsilylation. Methyl propiolate (107) and dimethyl acetylenedicarboxylate (113) were heated at reflux with diene 9 0 b and 92b in toluene to provide the cyclohexadiene adducts, which were easily oxidized to the corresponding diaryl ethers using DDQ in ~90% yields. Alkyne 107 was also reacted with diene 105 to provide 3-hydroxy-4-phenoxybenzoic acid methyl ester (116) m 49% yield. The diaryl ethers were characterized by IR, 1^ H NMR, l 3^C NMR and elemental analyses. N-Cbz-O-methyl-L-tyrosinol (129a) and (1R,2R)-N-Cbz-O-methyl- B-hydroxytyrosinol (136b) were synthesized by the condensation of Danishefsky's diene (124) with an acetylenic ketone, benzyl (R)-4-( 1-oxo-2-propynyl)-2,2-dimethyl-3- oxazolidinecarboxylate (120), which was derived from D-serine. Reduction of the ketone function in the adduct using NaBH_4 at 0°C provided 136b. Deoxygenation of the alcohol function in 136b via Barton's procedure gave the optically pure tyrosinol 129a. The synthesis of the fully differentiated (L,L)-isodityrosinol, ( 4R)-3-benzyloxycarbonyl-2,2-dimethyl-4- [3-[ 4-[ (2S)-2-( t-butyloxycarbonyl)amino-3-hydroxypropyl]phenoxy ]-4- methoxyphenylmethyl] oxazolidine (169) was also approached by a sequence of cycloaddition, aromatization and reduction. The cycloaddition between ketone 120 and diene 93b resulted in formation, in 91% yield, of an equal mixture of two regioisomers that were separated by flash chromatograph [...]
doi:10.26076/0133-ada6 fatcat:4dkl3pk5inc4xke4sum7pvc6lq