Total Synthesis Of Active Stilbene Dimers And Studies On Discovery And Application Of New PtCl₂-Catalyzed Transfer Hydrogenation Reaction

Active stilbene oligomers ε-Viniferin and Dehydro-δ-viniferin,having 2,3-diaryl dihydrobenzofuran or 2,3-diarylbenzofuran characteristic structure,were representative natural products of resveratrol dimers.ε-Viniferin and δ-Viniferin,the precursor of Dehydro-δ-viniferin,distributed mainly in the families of Vitacae,Dipterocarpaceae,Gnetaceae and so on.As reported in the literature,they showed significant anti-inflammatory,antibacterium,anti-oxidant and other biological activities.A few studies on their total syntheses have been reported up to now due to their complex structures.In this thesis,studies on the hydrogenation reaction of aromatic hydrocarbons involving metals were summarised and commenced,which provide valuable information for the investigation of the hydrogenation of aromatic hydrocarbons.With commercial 3,5-dihydroxybezoic acid and 3,5-dihydroxybenzophenone as starting materials,a facile and practical total synthesetic approach of naturally active ε-Viniferin has been achieved in 14 steps and 6.81%overall yield.Demethylation of the intermediate 2,3-diarylbenzofuran with methoxycarbonyl substituted at C-4 has been achieved through the exploration of deprotection method.Using TFA/TES as catalyst,reduction of the double bond of 2,3-diarylbenzofuran in the presence of hydoxyls was accessed for the first time.Selecting MOM as phenolic hydroxyl protective group of ε-Viniferin,Deprotection reaction was efficiently accomplished for the first time in the presence of unstable 2,3-diaryl dihydrobenzofuran ring and styryl double bond.The research results are helpful for the reduction of 2,3-diarylbenzofuran ring of polyphenols that is hard to be reduced and the selection of hydroxyl protective group in the reduction reaction.These results will also provide basis for the synthesis and investigation of structure-activity relationships of ε-Viniferin and its derivatives.On the basis of the total synthesis of Dehydro-δ-viniferin catalyzed by amberlyst 15,using metal-halogen exchange as key step,a versatile and practical total synthetic approach of Dehydro-δ-viniferin has been achieved in 10 steps and 20.6%overall yield with commercial 3,5-dihydroxy benzophenone and 4-hydroxybenzaldehyde as starting materials.Catalyzed by i-PrMgCl·LiCl,the synthesis of 3-aryldihydrobenzofuran from α-aryloxyketone diiodine through metal-halogen exchange was achieved for the first time.These results will provide basis for the synthesis and the investigation of structure-activity relationships of Dehydro-δ-viniferin and its derivatives.Using PtCl2 as catalyst,a highly efficient transfer hydrogenation reaction of aromatics and phenolics under unprecedented,mild conditions was studied and developed.Mechanism investigation indicated that the reduction of aromatic ring was proceeded via successive single electron transfer(SET)mediated by in situ-generated transition-valent platinum.Cyclohexanone(Cy=O)was proven to be the key intermediate in the hydrodeoxygenation(HDO)process.PtCl2-mediated transfer hydrogenation reaction can be performed effectively at temperatures as low as 20℃ to 30℃.Primary,secondary,and tertiary alcohols can serve as good H-donors and solvents.Acids and water have no negative influence on the process.Monocyclic and polycyclic aromatic hydrocarbons,and fused-ring and heterocyclic aromatic hydrocarbons were successfully converted into cycloalkanes and alcohols with good to excellent yields.These findings offer novel process options for hydrogenation(HYD)and HDO of aromatic and phenolic compounds.