Constructions Of Benzofuran And Aromatic Spirokedtal Skeletons

Benzofurans are ubiquitous structural motifs in a wide range of biologically active compounds which display various pharmacological activities. They are also regarded as the privileged pharmacophores and building blocks. Aromatic spiroketals are important subunits found in various biologically active natural products. Their unique aromatic spiroketal ring system has been proven to be essential for the biological activity of their parent compounds. Thus, the synthetic methodologies of these important structures have been drawing many organic chemists'attention. This dissertation mainly introduces two cascade reactions, which could easily construct the benzofuran and aromatic spiroketal structures from readily available starting materials. It consists of the following five parts:Chapter1. The Construction of2-methylene-3-hydroxy-benzofuran Structures via a New Cu'-Catalyzed CycloetherificationIn this chapter, we disclose a new copper catalyst system, which can catalyzed the cycloetherification of2-(1-hydroxyprop-2-ynyl)-phenol derivatives under very mild conditions. Based on this protocol, we synthesized12differentially substituted benzofurans. We found that the presence of benzylic OH group plays a crucial role in the cycloetherifications:When the OH group is protected, reaction rate was slower and the yield was lower; when there is no OH group, no reaction occurred.Chapter2. Cu'-Catalyzed Cycloetherification/Acid-catalyzed Allylic Nucleophilic Substitution for One-pot Synthesis of2-Substituted BenzofuransBased on the successful results introduced in chapter1, we then realized an efficient one-pot synthesis of2-substituted benzofurans. In the process of our investigation, we found that the steric factor of neoclephiles(alcohols) had deleterious effects on the allylic nucleophilic substitution and no rearrangement products were formed. Based on these results, we suggested the mechanism of this allylic nucleophilic substitution was SN2type, rather than the widely accepted SN1type.Chapter3. Cu'-Catalyzed Cyclization/Hydrogen-Bonding-Induced Asymmetric Hetero-Diels-Alder Cycloaddtion Cascade:An Approach to Aromatic SpiroketalsIn this chapter, we develop a novel and practical method for the diastereoselective synthesis of diversely functionalized3'-hydroxy-bisbenzannelated5,6-spiroketals via an unprecedented copper-catalyzed cycloetherification/asymmetric hetero-Diels-Alder cycloaddition cascade. We found that the base wasn't necessary for the cycloetherification process at high temperature(>100℃) and the hetero-Diels-Alder cycloaddition was stereoselective. A hydrogen-bonding between two reagents accounts for the novel syn-stereoselectivity. This stereoselectivity nicely complements the widely reported trans-stereoselective ones. Finally,18substituted cis-configured3'-hydroxy-bisbenzennulated5,6-spiroketals were synthesized in good yields.Chapter4. Studies on the Asymmetric Total Synthesis of Natural Product PeacilospironeIn this chapter, we report a concise converged synthetic route for the asymmetric total synthesis of peacilospirone. We have accomplished the model reaction and envisioned that the configuration of the double-bond on the cyclization product determined the strereochemistry of the spiroketal skeleton. We tried to synthesize one building block(Z-cyclization product) via two different methods, one of them failed, the rest is underway. The other building block will be obtained soon.Chapter5. Recent Progress on the Synthetic Methods of Benzofurans (Review)In this chapter, we display some novel and efficient synthetic methods of benzofurans. Beside the traditional synthetic route, we also introduce some seldom used methods, which can construct the benzofuran structure from different concepts. These methodologies include:rearrangement/cyclization cascade, construction of benzene rings, carbon-carbon bond formation and so on.