Studies On Organocatalyzed C-O Coupling Reactions And Gold Catalyzed C-C Coupling Reactions

The direct activation of C-H bond has been regarded as the "Holy Grail" of organic chemistry and an indispensable tool in the organic synthesis process.The direct C-H bond functionalization could reduce the reaction steps in multi-step synthesis and establish a more convenient way than traditional coupling methods such as Suzuki-and Negishi-coupling reaction,which would avoid the pre-functionalization process.In the past decades,the C-H bond activation has been thoroughly studied,developed rapidly and widely used in academia and industry.The modern methods of activating C-H bonds are mainly divided into three categories:1)using a free radical initiator to initiate the C-H bond cleavage;2)using carbene or nitrene for C-H bond insertion;3)metallization of C-H bond activation under C-metal intermediate forming,with metallization deprotonation and oxidative addition.However,the tedious operation of reagents and additives,which would cause certain toxicity and environmental pollution,is unavoidable.Therefore,achieving high-efficiency and environment-friendly catalytic activation has attracted a large amount of focus in the research area of direct activation of C-H bonds.Based on previous research of C-H bond activation,several kinds of pharmaceutical and chemical intermediates have been synthesized from terminal Csp-H or Csp3-H adjacent to oxygen,with high efficiency under the homogeneous reaction conditions in this research.The main research contents of this thesis are listed as below:1、Organocatalyzed C-H activation for the formation of C-O bondAs an important component of the bioactive molecular skeleton,C-O bonds widely exist in drug molecules,pesticide chemicals,materials and natural products.Direct construction of novel C-O bonds by catalytic activation of C-H bonds has been a research focus.In the second chapter,a-hydroxyamination of isochroman derivatives were successfully prepared via cross-dehydrogenation coupling of C-O bonds using tetra-butyl hydroperoxide(TBHP)as the oxidant and tetra-butyl ammonium iodide(TBAI)as the catalyst.The substrate scope was investigated under optimal reactions and most of isochroman derivatives bearing with either electron-donating or electron-withdrawing groups were obtained in good yields.In addition,preliminary mechanism studies provided some useful information for further application of this protocol in C-O bond formation.2、Gold-catalyzed intermolecular cycloisomerization between silylene and furanAs an important industrial material,2,5-dimethylphenol,mainly prepared by sulfonation alkali fusion method,has been used in the production of high-lipidemia drug and vitamin E,with large amounts of wastes coming along.In this chapter,several kinds of Au(I)catalysts were investigated to achieve the one-step preparation of 2,5-dimethylphenol by intermolecular cycloisomerization of silylene and 2,5-dimethylfuran.This work opens a new access to 2,5-dimethylphenol from 2,5-dimethylfuran,a typical biomass-based compound.3、Gold-catalyzed intermolecular cycloisomerization between aromatic alkyne and furan.The Au(I)complex catalyzed intermolecular cycloisomerization reaction was further extended to the reaction of 2,5-dimethylfuran with aromatic alkyne compounds.Further investigation on substrate scope showed that the reaction is well tolerant with various phenylacetylene derivatives with either electron-withdrawing or electron-donating substituents.The DFT computations using a simplified model reveals that the nucleophilic addition of Cβ of activated alkynes to Ca atom of furan is the rate-determining step.