Abstract
The studies on the development of methodologies to synthesize cis-decalins from 2-methoxyphenols via masked o-benzoquinones and their applications toward the synthesis of natural products are described. This thesis consists of three parts: the first part is concerned with novel methodologies to synthesize cis-decalins and the latter two parts deal with the studies toward syntheses of eremopetasidione and neotripterifordin, respectively. In the first part, oxidation of 2-methoxyphenols 33 using BAIB, followed by intermolecular Diels-Alder reaction with dienophiles 34, was carried out to produce the cycloadducts 35. The bicyclo[2.2.2]-octenones 35 were treated with Lombardo reagent and NEt3, TMSOTf to obtain the corresponding dienones 36 and 37 and the subsequent Cope rearrangement furnished cis-decalins 38 and 40 respectively. In this way we have developed a four-step sequence via oxidation, Diels-Alder reaction, double-bond formation and Cope rearrangement for the syntheses of cis-decalins. We have also carried out the oxidation of 2-methoxyphenols 33 in presence of dienols 43-47 with BTIB followed by intramolecular Diels-Alder reaction to get the tricyclo[4.3.1.03,7]decenones 56 and cis-decalins 57. The tricyclo[4.3.1.03,7]decenones 56 can be converted into cis-decalins 57 via Cope rearrangement. Thus, we have developed an efficient three-step methodology, i.e., oxidation, intramolecular Diels-Alder reaction and Cope rearrangement for the stereoseletive syntheses of highly substituted cis-decalins. Synthesis of eremophliane type skeleton 125 has been described in the second part. The cis-decalin 120 was prepared from 4-methyl-2-methoxyphenol employing the methodology described in the first part. The cis-decalin 120 upon treatment with 1% oxalic acid afforded the bicyclodecenediones 121 and 122. The reduction of 121 followed by hydrogenation and deketalization furnished the required naphthalenone 125. Our synthetic methodology provides an alternative route to eremophilane type skeleton 125 with total stereocontrol. Synthesis of cis-decalin 152 has been described in part 3. Alkylation of methyl vanillate followed by Claisen rearrangement and ozonolysis gave the phenol 150. Protection hydroxyl function of 150 followed by ketalization and deprotection of the acetoxy group produced phenol 144. By applying the methodology described in the first part for the 2-methoxyphenol 144, followed by hydrogenation, the cis-decalin 152 was obtained in an overall yield of 24 % in nine synthetic steps.