Studies On The Organohypervalent Iodine Catalyzed Cycloetherification:Construction Of Bisbenzannelated Spiroketals

Bisbenzannelated spiroketals exist widely in biologically significant natural products as important pharmacophores and is the key challenge for the total synthesis of natural compounds, so it is of major importance to development new efficient methods for constructing this unit. Aiming at exploring the new construction of spiroketals, these thesis developed two new clycoetherification conditions involveing a new method for the formation of hypervalent iodine reagent, based on which two new methods were developed for the construction of spiroketals:one through a four-step reaction cascade and the other through an intramolecular a-oxyphenylation of carbonyl compounds. It consists of three parts as follows:Chapter1. The progress on organohypervalent iodine and fluoride mediated oxidative reaction (review).This chapter introduced progress on the research of organohypervalent iodine reagents, including the preparation of organohypervalent iodine compounds, hypervalent iodine catalyzed reactions, and the main catalytic mechanism. According to the iodine sources and the reactions, four kind of reactions were discussed mainly:the reaction of iodobenzene catalyzed spirocyclizations of phenols, iodoarenes catalyzed a-oxygenations of carbonyl compounds, ionic (tetrabutylammonium iodide) catalyzed a-oxygenations of carbonyl compounds, iodine (Ⅲ)-catalyzed other reactions, and the applications of high-priced iodine catalyzed reactions in the synthesis of natural products. In addition, the chapter also introduces the fluoride ions mediated the oxidative reaction, including:the activation of C-Si bond oxidative reaction of fluoride ion and other reactions.Chapter2. New method for the construction of spiroketals through a four-step reaction cascade and the involved new hypoiodite catalyzed cycloetherification.Organohypervalent iodine was found high potential catalytic application value, especially in the α-functionalization of carbonyl compounds. Multi-steps cascade reaction and catalytic relay reaction have aroused wide and continue interest for their high efficiency and conviniency. For these reasons, a four-step cascade reaction was desighed to construct the bisbenzannelated spiroketal core and got good results. This cascade includes a hetero-Diels-Alder reaction, a silica gel-mediated hydrolyzation of amino acetal, a silica gel-mediated decarbonylationof acetal, and in situ generated hypoiodite-catalyzed cycloetherification of carbonyl compounds. All of these experiments showed that irradiation, TBAI, and oxygen are obligatory, TBAF is a good auxiliary reagent for this transformation. A mechanism was hypotheisized where TBAI was converted to hypoiodite or hyperiodite under areoic irradiation and then catalyzed the cycloetherification. This is a new catalytic application of hypoiodite reagents and a new preparation method of hypoiodite. It is also the first case using hypoiodite in the construction of spiroketals. In this cascade, silica gel and TBAI acted as catalysts in succession, forming acatalytic relay, especially the TBAI for the cycloetherification generated from the first cycle HDA.Fluoride was found necessary for the high efficient transformation, which is an important development of the application of fluoride ion.Chapter3. New method for the constructing spirketals catalyzed by hypoiodite generated in-situ from oxidation of iodide by peroxide acids.In this chapter, a new hypoiodite-catalyzed cycloetherification using mCPBA as oxidant, TBAI as iodite source were developed to construct the bisbenzannelated spiroketal cores. So a new modified condition were found to be as follows:2.0eq. of TBAF as additive,15mol%of TBAI as catalyst source, and2.0eq. of mCPBA as oxidant were stirred at room temperature with3-1in THF as solvent in5minutes.This method provides a quick and efficient route to construct the bisbenzannelated cores. The possible mechanism was proposed. The electron effect of substituents in substrates was investigated and the fluoride was found to be obligatory for this cycloetherification as an activator.The above work also showed high potency in the stereoselective synthesis of enantiomeric spiroketals, the main challenge for the synthesis of natural products like rubromycins.