Studies On Tandem Cyclization Of Alkynones And Trifluromethylation In Water At Room Temperature

The thesis mainly studies on tandem cyclization of alkynones and trifluoromethylation in water and at room temperature, which includes three chapters as followed:Chapter 1Part 1. Investigation on alkynones in various organic reactionsAlkynone as one of the most important intermediates in organic synthesis and pharmaceutical chemistry was widely used. Due to its di-functionality, the carbonyl group and the alkynyl group can be mutual activated, which resulting this kind of compounds with unique selectivity and diversified. Here, we mainly described the transition metal catalytic isomerization of alkynones including hydrosilylation and hydrostannylation, transition metals and organic reagent catalytic conjugate addition of alkynone compounds, alkynone derivatives involved in various of tandem cyclization reactions, such as tandem cyclization of alkynones via transition metal catalysis, electrophilic cyclization, or under metal-free conditions.Part 2. Summary of green chemistryGreen chemistry efficiently utilizes chemo- and bio-catalysis and non-conventional reaction media in eliminating waste and circumventing the use of hazardous reagents and solvents, is widely concerned and embraced by the chemical industry and the academic community. Mechanochemical mixing, ultrasonic irradiation, microwave heating and the use of green solvents or nanomaterials are the mainly approaches to realize Green Chemistry. Meanwhile, the measurements for Green Chemistry such as Trost’s atom economy (EA), Roger Sheldon’s environmental factor (E-factor) and the similar metrics were already known. Due to its rapid evaluation of the amounts of waste generated by manufacturing processes, E-Factor has now become a widely accepted green metrics. Recently, function factor (F-factor) has become a new simple metric, which could enable people to compare the amounts of different chemicals needed to provide a particular function.Chapter 2Part 1. Lewis-acid-catalyzed/mediated the tandem reactions of alkynonesCompared with the synthetic approaches for indoles, Lewis-acid was proven to be the most efficient catalyst. Thus, various Lewis-acids with alkynones were screened When Sc(OTf)3 was used as a catalyst, highly substituted indoles through an intramolecular Friedel-Crafts reaction was obtained. While SnCl4 was employed, highly Z-selective C-C1 bond formation was successfully formed. The resulting C-Cl bond can be further exploited using cross coupling reactions.Part 2. Br(?)nsted acid catalyzed cycloisomerizations of alkynones for the synthesis of dihydropyranonesBased on the previous report on iodonium-induced carbocyclizations of hydroxylated alkynes, we tried to get 5,2-enyne-l-ones via further oxidation of the substrate. In the presence of acid, proton from the acid first interacts with carbonyl oxygen. Then alcohol as a nucleophile attacks the carbon-carbon triple bond, which undergoes a final cycloisomerizations produces dihydropyranone. During the study, Br(?)nsted acid was proven to be the most efficient catalyst, meanwhile intermediate was isolated successfully and a deuterium-labeling experiment was performed to prove the proposed mechanism of this cycloisomerization.Part 3. Br(?)nsted acid-catalyzed and iodine-promoted tandem cyclization of alkynones for the synthesis of benzene derivativesOn the study of Br(?)nsted acid catalyzed cycloisomerizations of 5,2-enyne-l-ones, we found that when substitute on the alkenyl group was changed from aliphatic group to aromatic group, the corresponding dihydropyranone product was not detected, but a benzene derivative was obtained. To further study the mechanism, we used iodine as electrophile to process the reaction in alcohol and aprotic solvent nitromethane, finally iodoalkoxy- and diiodobenzene derivatives were obtained, respectively. For these reactions, highly substituted benzene derivatives, including alkoxy-, iodoalkoxy-, and diiodo-substituted benzenes can be directly and highly selectively synthesized with different reaction systems, which provided a new shortcuts and methods for the synthesis of benzene derivatives.Chapter 3 Copper-catalyzed trifluoromethylation in water at room temperatureIn the context of our ongoing efforts in developing new generation surfactants, we developed an inexpensive Cu salt catalyzed trifluoromethylation in water at room temperature for the synthesis of oxindole derivatives. Compared with the previous trifluoromethylation with precious metal and expensive trifluoromethylating reagent, this reaction employed cheap and readily available Cu salt and inexpensive Langlois’ reagent as CF3 source. Perhaps most noteworthy would be the mild reaction conditions using water as the reaction medium, with no investment of energy beyond that provided at ambient temperatures. Moreover, additional advantages include the ease of handing all components in air, the environmentally friendly nature of having eliminated organic solvents from reaction mixtures thereby minimizing organic waste, and the opportunity to recycle the aqueous medium.