Studies On Pd/Au-catalyzed Intramolecular Cyclization Between Hydroxyl And Multiple Bond: Synthesis Of The Bis-benzannelated Core Of Rubromycins

This dissertation aims at the studies on the construction of the bis-benzannelated[5, 6]-spiroketal core of rubromycins via palladium/gold catalysis and the synthesis of 2-substituted benzo[b]furan compounds via gold catalysis.It consists of the following four parts:Chapter 1.Structure,Biological Activities and Syntheses of the Rubromycins Family (review).The isolation,structural characterization,biological activities,and syntheses of Rubromycins,especially the construction of the bis-benzannelated[5,6]-spiroketal core of rubromycins family were summarized.Chapter 2.Gold-Catalyzed Double Intramolecular Alkyne Hydroalkoxylation:Synthesis of the Bis-benzannelated Spiroketal Core of Rubromycins.The syntheses of oxo-heterocyclic compounds via palladium and gold-catalyzed intramolecular hydroalkoxylation were introduced briefly.Using the readily available o-iodophenols and allyloxybenzene as starting materials,alkynyl diphenols were obtained after several effective steps.2-30a was then used as model substrate to explore the conditions of the intramolecular hydroalkoxylation via palladium/gold catalysis.The experiments showed:palladium reagents mainly gave 2-substituted benzofuran 2-32a in high yield and only a small quantity of spiroketal 2-31a was obtained;gold regents mainly gave spiroketal 2-31a;PPh₃AuCl/AgOT was the optimal catalyst.In the presence of 10 mol%of PPh₃AuCl/AgOT,various substituted[5,6]-aromatic spiroketal skeletons were synthesized in 46～62%yields in CH₂Cl₂.A contrastive study on the formation of aliphatic and of aromatic spiroketals has also been conducted,which showed that aliphatic hydroxyl group has higher nucleophilicity than phenolic hydroxyl group toward the gold-complexed triple bond.The benzofurans can also transfer to the corresponding spiroketals in the presence of 10 mol%of PPh₃AuCl/AgOT,which showed that benzofurans were the intermediate of the gold-catalyzed cyclization.Hence a tandem cyclization mechanism was proposed.It was for the first time that gold-catalysis was used in the formation of the bis-benzannelated spiroketal core of rubromycins.The process would serve as a good complement to the existing methodologies and its very mild reaction conditions would allow further applications toward the total synthesis of rubromycins.Chapter 3.Palladium-Cactalyzed Intramolecular Wacker Reaction:Synthesis of the Bis-benzannelated Spiroketal Core of Rubromycins.The syntheses of oxo-heterocyclic compounds via palladium-cactalyzed intramolecular wacker reaction were introduced briefly.Using substituted benzaldehydes and substituted phenylpropyl sulphones as starting materials,a series of olefins with diphenolic hydroxyl groups were synthesized via Julia olefination.Using 4-16 as a model substrate,the conditions for the synthesis of bis-benzannelated[5,6]-spiroketal via intramolecular wacker reaction were explored.The experiments showed that 10 mol%PdCl₂/1.0 eq.CuCl/O₂/DME/reflux was the optimal reactive condition so far,under which the spiroketal 2-31a was obtained in 33%yield.It was for the first time that intramolecular wacker reaction was used in the formation of the bis-benzannelated spiroketal core of rubromycins.The subsequent researches are currently under investigation.Chapter 4.Gold-Catalyzed Alkyne Hydroxylation:Synthesis of 2-Substituted Benzo[b]furan Compounds.The syntheses of benzo[b]furan compounds were introduced briefly.Using the readily available 2-alkynyl phenol 4-9a as starting material,the conditions for the synthesis of the 2-substituted benzo[b]furan 4-10a via gold-catalyzed intramolecular hydroalkoxylation were explored.The experiments showed that 2 mol%PPh₃AuCl/AgOTf/CH₂Cl₂ was the optimal reactive condition,which allowed for the syntheses of various 2-substituted benzo[b]furan compounds in 84～98%yields.Our method was the first general methodology for the syntheses of the 2-substituted benzo[b]furan compounds via gold catalysis.