Study On Reactions Based On Maleimides And The Synthesis Of Indolylmaleimide Analogues

Maleimides are important building blocks in organic synthesis and have widespread applications in the fields of natural products,materials and bio-pharmaceuticals.Especially,indolylmaleimide analogues have a wide range of biological activities and fluorescence property because of their novel structures.Both the reactions based on maleimides and the synthesis of indolylmaleimide analogues have been discussed in context.And the whole work contains six chapters:Chapter ?: In this part,progress on the discovery,modification and application of indolopyrrolocarbazoles and indolylmaleimides natural alkaloids are reviewed.In the meantime,the synthetic methods of indolylmaleimides reported in the literature are summarized.The previous progress of our group in this field has also been showed.As we all know,maleimides contain the components of unsaturated imide and electron deficient carbon-carbon double bonds.And maleimides are easy to take part in the reactions such as Michael addition,Diels-Alder reactions and are susceptible to strong acid,strong base and high temperature.Schemes were designed to research on the reaction activities of maleimides and the synthesis of indolylmaleimide analogues in this paper.Chapter ?: Lewis acids catalyzed Michael additions of maleimides with indoles,pyrroles and arenes have been studied.We screened out the highly efficient Lewis acids working as catalysts in the reactions,such as Zn Cl2,Zn Br2,Al Cl3 and BF3.Et2 O.A series of 3-(indol-3-yl)succinimides,3-(pyrrol-2-yl)succinimides,3-phenylsuccinimides have been prepared.And the exact sturctures of the products in the reactions of maleimides with indoles and pyrroles were confirmed via single crystal X-ray diffraction analysis.Among,the preparation of 3-(indol-3-yl)succinimide derivatives had a wide range of scope with yields of 82%-95%.And the protocol had been successfully used in the synthesis of indolylmaleimides and bisindolylmaleimides.Both the symmetrical and the unsymmetrical bisindolylmaleimides could be prepared via this method with the free NH group of indoles and maleimides.Chapter ?: BF3.Et2 O catalyzed hetero-Michael additions(C-O,C-S,C-N froming)of maleimides with hetero atoms had been studied.Interestingly,the hetero atoms reacted with maleimides via different ways.1,2-Oxa Michael addition occurred using maleimides and alcohols as substrates.Fumaric acid analogues were obtained with the yields of 45%-92%.And 3-sulphur alkyl succinimides were obtained via 1,4-thio Michael addition with the yields of 77%-96%.3-Amino succinimides were obtained via 1,4-aza Michael addition with the yields of 34%-90%.Especially,the rearranged products were obtained with the use of 5-phenyltetrazole in the reaction,and the exact structures were confirmed with single crystal X-ray diffraction analysis.Chapter ?: An efficient Pd(II)-catalyzed approach for the direct synthesis of 5H-indolo[3,2-a]pyrrolo[3,4-c]carbazole-6,8(7H,13H)-diones have been developed from indoles and maleimides via two successive oxidative Heck reactions and the final thermal electrocyclization with the yields of 55%-85%.Meanwhile,indolylmaleimides were synthesized from 2-subsitituted indoles via the oxidative Heck reaction with the yields of 77%-88%.In addition,further studies show that indolylsuccinimides could efficiently be oxidized to indolylmaleimides via oxidative Heck reaction.And dipyrrolocarbazoletetraones could also been obtained from indolylmalimides via oxidative Heck reaction with high yields.The plausible mechanism of Pd(II)-catalyzed oxidative Heck reaction were discussed.And it provides an efficient and practical way for the modification of indolylmaleimide analogues.Chapter ?: Oxidative amination and amino-halogenation of maleimides have been discussed in this chapter.A simple,efficient,and practical way to prepare 3-aminomaleimides and 3-amino-4-arylmaleimides have been developed.The optimal condition proceeds in the presence of 0.2 mol% Cu(OAc)2,0.2 mol% Ag2CO3 at 120? in Ph Cl opening to the air.The products have a wide range of scope with yields of 21%-95%.Furthermore,the method for the synthesis of 3-amino-4-halogen maleimides was developed,including 3-amino-4-chloromaleimides,3-amino-4-bromomaleimides and 3-amino-4-iodomaleimides.The reaction has a short step and is easy to operate.Especially for 3-amino-4-chloromaleimides,the reaction has a wide range of scope with yields of 62%-92%,and provides a useful synthon to modify maleimides analogues.However,3-amino-4-bromomaleimides and 3-amino-4-iodo-maleimides have poor stability and bad substrate scope.Chapter ?: In this chapter,as a continuous for oxidative amination of maleimides with anilines,we did a study for the supplement of chapter IV since azobenzene was isolated and identified as a byproduct from the reaction of anilines with maleimides in the presence of oxidative protocol.And a practical,efficient way to obtain azobenzene derivatives have been developed from anilines in the presence of 2 equivalent of Ag2CO3 and 2 equivalent of KOC(CH3)3 in Ph Cl at 120? in the air.The yields were around 36%-92%.In the meantime,it enlightened us to improve the oxidative amination reactions of maleimides with anilines using acetic acid as solvent to extend the substrate scope.In conclusion,totally 133 compounds are synthesized,of which,69 compounds are new and have not been reported in the literature.And their structures were confirmed by melting point,IR,1H NMR,13 C NMR,MS,HRMS,X-ray and so on.