Studies On The Tandem Reactions Of Gem-Dihalovinyl Systems

A tandem reaction or cascade reaction or domino reaction is a consecutive series ofintramolecular and intermolecular organic reactions which often proceed with highlyreactive intermediates. It allows the organic synthesis of complex molecules from asimple strating material. The substrates with many functional groups can take part inorganic transformations at the time. The advantages of a tandem reaction are that thereaction is often fast owing to its intramolecular nature, the reaction is clean, displayshigh atom economy, avoids workup and isolation of intermediates, and exhibites muchcomplexity in effectively one step. Therefore, the suitable designed tandem reactionsare of great significance to organic chemists. gem-Dihaloolefins have been commonlyused as intermediates in organic synthesis because of their higher reactivity and readyaccessibility from aldehydes, which also widely used in the preparation ofpharmaceuticals, pesticides, materials, and fine chemicals. In recent years,gem-dihaloolefins have received great attention, especially for the synthesis ofheterocycles through transition-metal catalyzed coupling reactions. In this thesis, aseries of tandem reactions on the basis of gem-dihaloolefins as starting materials weredeveloped for the construction of benzofuran, benzothiophene and indole derivatives,which have potential biological activity. This thesis consists of the following contents.1.2-Arylbenzofurans and2-arylbenzothiophenes were prepared through an efficienttandem elimination–intramolecular addition–Hiyama cross-coupling reaction by using2-（gem-dibromovinyl）phenols（thiophenols） and phenyltrimethoxysilane as startingmaterials. In the presence of tetra-（n-butyl）ammonium fluoride （TBAF）, palladium（II）acetate [Pd（OAc）2] and triphenylphosphine （PPh3）, the reactions of2-（gem-dibromovinyl）phenols（thiophenols） with phenyltrialkoxysilanes proceededsmoothly and generated the corresponding products with good yields in one-pot. Itshould be noted that TBAF plays an important role in the tandem reaction. A proposalreaction mechanism was discussed and some controlled experiments were done to verify the possibility. Comparing with the boron reagents, the advantages of this methodare relatively more stable of organosilanes, less byproducts in the reaction, and moreenvironmental friendly.2. An efficient synthesis of2-selenyl（sulfenyl）benzofurans has been accomplishedthrough a copper（I）-catalyzed tandem reaction of2-（gem-dibromovinyl）phenols withdiorganyl diselenides and disulfides in the presence of CuI/Mg/t-BuOLi in DMSO.Using this protocol, a variety of2-selenyl（sulfenyl）benzofuran derivatives wereobtained in good yields. A variety of functional groups, either on the benzene rings of2-（gem-dibromovinyl）phenols or diorganyl diselenides and disulfides are all tolerated.Moreover, dialiphatic disulfides can also react with2-（gem-dibromovinyl）phenols,leading to a wider range of substrates. Some deuterated experiments were conductedand a possible reaction mechanism was proposed in the presence of copper catalyst.3. A novel and efficient strategy for the synthesis of2-bromo（chloro）-3-selenyl（sulfenyl）indoles through the tandem reactions of2-（gem-dibromovinyl）-N-methylsulfonylanilines with diorganyl diselenides anddisulfides in the presence of t-BuOLi and I₂in DMSO was developed. In addition,2-（gem-dichlorovinyl）-N-methylsulfonylanilines can also react with diorganyldiselenides and disulfides. A reaction mechanism, which has been verified by thedeuterated experiments, was proposed. The reactions generated the desired products ingood yields with high regio-selectivity under transition-metal-free conditions in one-pot.It provides a new route to indole derivatives.