Synthesis And Methodology Of Complex Compounds:[4+3]Cycloaddition,2-Aromatic Allylic Alcohols Isomerization And Synthetic Study Of Ibuprofen And A Dimer Of Thymol Derivative

This thesis was concerned with the studies on regioselectivity and stereoselectivity [4+3] cycloaddition reaction towards fused5,7,6-tricyclic skeletons and2-aromatic allylic alcohols isomerization and the total synthesis of a dimer of thymol derivative. It mainly consists of the following four parts:Part one:The [4+3] cycloaddition reaction:heteroatom-substituted allylic cations as dienophiles (review).In this part, a summary of the exploration and development of [4+3] cycloaddition chemistry of heteroatom-substituted allylic cations is presented. This review will classify and summarize from substituted heteroatoms and reaction systems for that type of reaction and applications of the methodology in the total synthesis of natural products also will be included.Part two:[4+3] cycloaddition reaction towards fused6,5,7-tricyclic skeletons.A [4+3] cycloaddition reaction towards fused5,7,6-tricyclic skeletons between heterocycle alcohols and a conjugated dienes is described herein. Meanwhile, the cycloadditions showed very excellent regioselectivities, good stereoselectivities. Furthermore, an interesting chemoselectivity was observed that the reaction of indole alcohols easily happened under the treatment of ZnCl2, however benzofuran alcohols didn’t in the same condition, but proceeded under Tf2O/2,6-lutidine. The mechanism of the cycloadditions was investigated and the synthetic usefulness has been shown by20examples, yield up to94%and d.r. up to99:1. The reaction providing a simple, efficient, and practical method for synthesis of the fused5,7,6-tricyclic skeletons included benzofuran, benzothiophene and indolePart three:2-aromatic allylic alcohols isomerization reaction. This part was concerned with the study on2-aromatic allylic alcohols isomerization reaction. By optimizing the reaction conditions via a catalytic amount of PPh3/CBr4. we developed an efficient method for2-aromatic allylic alcohols translate into corresponding saturated aldehydes or ketones. The synthetic usefulness has been shown by12examples, yield up to97%. The reaction providing a total atom economy method for synthesis of2-aromatic carbonyl compounds. This new methodology has been successfully applied to the synthesis of ibuprofen in4steps in46%overall yield.Part four:Synthetic study of a dimeric thymol derivative.The dimeric thymol derivative(4-1) separated from Arnica sachalinensis is a diterpenoid compound, having antifeedant activity for Spodoptera litura. On the basis of the symmetrical characteristic, oxydative degradation process, biosynthesis of natural product4-1, we designed four synthetic routes for the total synthesis of4-1. From commercially available1-(2-hydroxy-4-methylphenyl)ethanone (4-14) and3,6-dimethylbenzofuran(4-63), the notable feature of the synthesis was the use of reaetion sueh as Sharpless asymmetric dihydroxylation, Swern oxidation, free radical coupling reaction by Mn/CuCl2. Finaly, we synthesized the key intermediate compound4-44(in6steps in12%),4-11(in4steps in53%) and4-56(in8steps in36%). The related synthetic work is still in progress. The work not only detailed exploration for the synthesis of the natural products, but also accumulated some experience would be voluable to the continued investigations.