合成路线1

Synthesis of intermediate 1,4-bis(3,4,5-trimethoxyphenyl)butane-1,4-dione (V). This compound can be obtained by three related methods: 1. The Grignard reaction of 3,4,5-trimethoxybenzaldehyde (I) with vinylmagnesium bromide (II), followed by oxidation with MnO2, gives 1-(3,4,5-trimethoxyphenyl)-2-propen-1-one (III), which is then condensed with aldehyde (I) by means of the thiazolium salt (IV) to yield the target intermediate (V). 2. The condensation of 3,4,5-trimethoxyacetophenone (VI) with methylamine and formaldehyde gives 3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)-1-propanone (VII), which is treated with methyl iodide at 80 C to afford the previously reported propenone intermediate (III). 3.The direct dimerization of acetophenone (VI) by means of LDA and CuCl2 also gives the target intermediate (V). Synthesis of the target compound: The reduction of the butanedione intermediate (V) with LiAlH4 or NaBH4 gives (RS,RS)-1,4-bis(3,4,5-trimethoxyphenyl)butane-2,3-diol (IX), which is dehydrated to the target tetrahydrofuran by means of TFA, PdCl2/Cu(NO3)2 or MsCl/pyridine. Alternatively, the reduction of butanedione (V) can be performed stepwise, first with LiAlH(O-tBu)3 to give the intermediate hydroxyketone (VIII), which is reduced to the diol (IX). The isolation of the intermediate hydroxyketone (VIII) allows the separation of enantiomers offering the possibility of obtaining chiral forms of the target tetrahydrofuran.