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Chiral Tridentate Schiff-Base/Metal Complexes Catalyzed Asymmetric Friedel-Crafts Alkylation Reactions

Posted on:2014-02-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:F F GuoFull Text:PDF
GTID:1221330398959066Subject:Organic Chemistry
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Driven by natural product research and modern pharmaceutical industry, chiral heterocyclic compounds have attracted more and more interest as key structure moieties in these areas. The construction of these chiral structures consequently became a hot and challenging topic in the chemistry community. Friedel-Crafts alkylation of electron-rich aromatics with electron-deficient double bonds is one of the most powerful reactions to form C-C bonds. The enantioselective version of this classic reaction could be a promising tool for the construction of chiral aromatics, including chiral heterocyclic compounds.Indole and pyrrole are two fundamental structures in heterocyclic chemistry. Based on these two structures, we developed three efficient enantioselective Friedel-Crafts alkylation reactions to construct their chiral derivatives. Meanwhile, we designed and synthesized some new Lewis-acid catalysts based on chiral tridentate Schiff-base ligands.We have four chapters in this dissertation:In Chapter1, we summarized the applications of chiral tridentate Schiff-base ligands in asymmetric Lewis-acid catalysis. And a brief introduction of progress in enantioselective Friedel-Crafts alkylation was also included in this chapter.In Chapter2, we studied the enantioselective Friedel-Crafts alkylation of indoles with nitroalkenes. By applying the concept of combinatorial transition-metal catalysis, we designed a new Schiff-base/Zn catalyst using piperidine as combinatorial ligand. The new catalyst was successfully applied in the target reaction, giving adducts in high yields and excellent enantioselectivities. Single crystal structure of the catalyst was obtained and a bifunctional working mode in transition-state was proposed base on this. Moreover, we found that this new catalyst complex is stable under air atmosphere for at least6months.In Chapter3, the Friedel-Crafts alkylations of pyrroles with nitroalkenes were investigated. These reactions could be successfully catalyzed by a new tridentate Schiff-base/Cu complex, giving the products in unprecedented high yields and ees. Very good regioselectivities could also be obtained when3-and (or)4-substituted pyrroles were applied. Synthetic utility of this method was demonstrated in the preparation of Nicotine derivatives. Furthermore, nonlinear effect study and kinetic study were carried out to get insights into the reaction mechanism. It is also noteworthy that, this catalytic system exhibited very good tolerance to water.In Chapter4, we described the enantioselective Friedel-Crafts alkylation of pyrrole with isatins. Under the catalysis of a tridentate Schiff-base/Cu complex, a series of chiral3-hydroxy-2-oxindoles were obtained in excellent yields and ees, which could have a lot of potential bioactivities. In the case of N-unprotected isatin, the high reactivity of substrate was tamed by using a novel Henry/retro-Henry slow-release strategy.Besides these four chapters, graphical abstract, new compound list and some representative spectrums are also appended at the end of this dissertation.
Keywords/Search Tags:asymmetric catalysis, combinatorial catalysis, Friedel-Crafts alkylation, retro-Henry reaction, Schiff-base, nitroalkene, indole, pyrrole, isatin
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