| Self-organization behavior of small molecule cluster is an important medium to reveal the chemical process and operative mechanism of life. And the expression of the traditional self-organizing behavior is based on weak interaction forms of non-covalent bond of small molecule cluster. However, to this day, it's unclear whether there is molecular self-organization behavior in the chemical reaction with respect to the formation and cleavage of covalent bond. Therefore, we hope to explore the molecular self-organization behavior of chemical reaction and design logically the self-organization reaction system for the construction of heterocyclic skeleton looking for more effective synthesis method to realize the molecular self-organization behavior across from non-covalent bond to the covalent bond. Based on our research, it is consider that "the self-organization reaction system" is one type of integration reaction formed according to the chemical structure of logic transformation relationship and rational design combination of the diversity of independent organic unit reaction serving as the basic component, which is a highly complex chemical reaction system. The research of this system could not only make us understand and recognize the self-organization behavior of microscopic particles, but also provide a very effective medium for its existing forms and level, and at the same time it's also the new starting point that we further reveal and find the self-sorting behavior of molecular cluster. In addition, it provides a new strategy and idea of efficient green synthesis approach to the complex structure.In this thesis, based on the ary1 methyl ketone sp3 C-H with Kornblum oxidation as the key organic reaction, a systematic research on the logical integration of known organic unit reaction for the node was made by the single-linear integration model, the double-linear convergent integration model of the in situ cross-trapping strategy and the three-linear convergent integration model of the in situ generation and application of the center molecular skeleton. The main contents are as follows:In chapter 1, we first briefly summarize the self-organization reaction system theory, and then review the application and progress in construction of heterocyclic compounds via the domino name reaction, the domino cross dehydrogenation coupling cyclization reaction, the domino oxidation coupling cyclization reaction, the successive C-H activation cyclization reaction, the multicomponent cyclization reaction with a-oxoaldehydes from the basic component of the self-organization reaction system. Subsequently, we put forward the research idea.In chapter 2, base on the single-linear integration of iodination, Kornblum oxidation, condensation, intramolecular cyclization and aromatization, we develop a molecular iodine promoted domino oxidative cyclization process to construct oxazole derivatives from easily available aryl methyl ketones and benzylic amines, and realized the total synthesis of natural products balsoxine, texaline, uguenenazole, texamine and halfordinol in one-pot for the first time. It is notable that this metal-free and peroxide-free transformation involves dual functionalization of two types of C(sp3)-H bonds (sp3 a-C-H of carbonyl and sp3 a-C-H of nitrogen atom).In chapter 3, base on the single linear integration of iodination, Kornblum oxidation, oxidative cyclization and deacylation, we develop a new strategy for the synthesis of 1,3,4-oxadiazoles through direct annulation of hydrazides with aryl methyl ketones. It is found that the use of K2CO3 as a base achieves an unexpected and highly efficient C-C bond cleavage to realize the methyl ketone as methylating reagent construction of heterocyclic compounds for the first time.In chapter 4, on the basis of the above two chapters, with Povarov reaction as the core organic unit reaction, a highly efficient formal [3+2+1] cycloaddition reaction for the direct synthesis of substituted quinolines from aryl methyl ketones, arylamines, and styrenes is developed. The methyl group of the methyl ketone represents uniquely reactive input in the Povarov reaction for the first time. Mechanistically, the key step in our newly discovered Povarov reaction involves the C-acylimine in situ generated as the key intermediate.In chapter 5, with cross dehydrogenation coupling as the core organic unit reaction, the C3-dicarbonylation of indoles is realized through direct oxidative cross-coupling of indoles with aryl methyl ketones in the presence of molecular iodine and pyrrolidine. It is feasible that the aryl methyl ketone serve as double carbonylation reagent. Preliminary mechanistic study indicates that molecular iodine direct rapid oxidation of hydroxyl to carbonyl by colud also complete the conversion process.In chapter 6, with oxidative coupling as the core organic unit reaction, a highly efficient molecular iodine promoted the synthesis of naphtho[2,1-b]furan-1(2H)-one with a quaternary carbon center has been developed by using directly 2-naphthols as dinucleophilic point. In the process of this transformation, molecular iodine gives full play to its oxidant properties to avoid dehydration process and make oxidation of cross-coupling happen.In chapter 7, base on the double-linear convergent integration of iodination, Kornblum oxidation, ring-opening of benzothiazoles, condensation, Michael addition, oxidative aromatization, we design logically an I2/KOH synergistically promoted aroylation of benzothiazoles via the in situ cross-trapping strategy. It reveals that aryl methyl ketones are seen to act as potential carbonyl sources, providing new design ideas for the acylation of hybrid aromatic ring.In chapter 8, base on the double-linear convergent integration of iodination, Kornblum oxidation, oxidative amination, aldol reaction, a novel molecule iodine promoted the in situ cross-trapping strategy has been developed involving the direct use of acetamides and aryl methyl ketones for the construction of 3-(methylthio)-4-ary1-1H-pyrrole-2,5-diones. It shows a synergy of molecular iodine and DMSO.In chapter 9, on the basis of chapter 8, we design logically the first known example of convergent integration of the three-linear reaction with the in situ generation and application of a-ketoimides. Acetamide is generated in situ from acetonitrile in the presence of by-products HI in the system. This protocol realizes the possibility of potential applications of molecular from the small molecules assemble via convergent integration of three self-sorting domino sequences.In chapter 10, based on the design principle of chapter 9, we design logically feasible scheme of convergent integration of the three-linear reaction with the in situ generation and application of imidazo[1,2-a]pyridines. The key of this reaction is the clever introduction of organic reagents NH2CN to avoid Kornblum oxidation and be conducive to imidazo[l,2-a]pyridines generated in situ. It shows the potential guidance value in the design of self-organization reaction system for building multifunctional heterocyclic compounds.In chapter 11, based on the coproduct catalyzed domino strategy, A highly efficient molecular iodine catalyzed Povarov-type reaction of aryl methyl ketones, arylamines, and a-ketoesters is developed. HI, generated in situ from the upstream iodination and Kornblum oxidation steps, served as a promoter for the downstream Povarov step, which shows self-organization reaction system makes full use of the advantages of internal resources to improve the atom economy.In chapter 12, based on the steping integrated domino strategy, we develop an efficient approach toward 3,6-diarylpyridazines and 6-arylpyridazin-3-ones from simple and commercially available 1,3-dicarbonyl compounds and aryl methyl ketones without any catalysts and additives by changing DMSO to t-BuOH. Then excess amount of hydrazine hydrate as a nucleophile could attack the carbonyl group to eliminate hydrazide.In chapter 13, all the works of this thesis are summarized, and the two typical problems of the allosteric phenomenon and fluctuation effect are analyzed for further research on complex self-organization reaction system to provide an important entry point and research approaches. |
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