Copper-Catalyzed C-N, C-S (Se) Coupling Reactions And Palladium-Catalyzed Desulfitative Conjugate Addition Reaction

Transition-metal-catalyzed cross-coupling reactions are universal protocols in organic synthesis. Among them, copper played a significant role and made an important breakthrough in the past years. However, limitations still exist, such as catalytic efficiency, ligand complexity, poisonous reaction medium and the separation for products. Thus, to explore highly efficient, highly selective and recyclable catalyst including environment-benign catalytic system is the trend for the development of coupling reactions.Beside the transition-metal-catalyzed coupling reaction, the conjugate addition of organometallic reagents to α,β-unsaturated carbonyl compound is also an important synthetic tool for constructing C-C bond. However, the organometallic reagents are generally expensive, poisonous, unstable and basic componuds. The challenge to find alternatives to the conventional transmetallation method for the formation of organometallic intermediate still is has a significant way to go for researchers.Thus, five parts were carried out based on the coupling reaction and the conjugate addition reaction.(1) Based on the self-accelerative effect of2-aminophenol. we developed the ligand of1,2,3,4-tetrahydroquinolin-8-ol. It indicated that this ligand was very efficient to promote the copper-catalyzed C-N coupling reaction of amines and azoles with aryl bromides under mild conditions.(2) A wide range of free N-H2-arylindoles were synthesised via the copper-catalyzed amination of2-bromo-arylacetylenes with aqueous ammonia and sequential intramolecular cyclization. This route, avoiding of the amino-group protection and deportection, makes it atom economy and also provides a convenient route for the synthesis of indoles.(3) Based on the coordination of solvent, we designed a new reaction system for ligand-free copper-catalyzed C-S coupling reaction. With only1mol%of Cu2S as the catalyst, iron powder as additive, and K2CO3as the base, the coupling reactions of aryl iodides and disulfides were able to provide good to excellent yields of aryl sulfides.(4) The heterogeneous Cu2S@FexOy catalytic system for C-Se coupling reaction was investigated. The coupling reactions between aryl halides and diaryl diselenides were able to accomplish in only3-12h with good to excellent yields. SEM-EDX is used to analyze the structure and elemental composition of catalyst before and after reaction and it indicated that the addition of Fe played an important role not only reduced CuS to form the real catalyst Cu2S but also reacted with DMSO to generate FexOy as support to accelerate the reaction.(5) The palladium (Ⅱ) catalytic desulfitative conjugate addition of arylsulfinic acids with α,β-unsaturated carbonyl compound was investigated. With the optimized condition, the conjugate reaction was carried out at90℃with good yields and high selectivity. ESI-MS/MS was used to capture the reaction intermediates and it suggested that the reaction pathway involved the desulfitative of arylsulfinic acids, formation of C=O-Pd, migratory insertion via the C-Pd intermediate to generate the O-Pd enone and protonolysis. The in situ generated cationic palladium (Ⅱ) intermediates were demonstrated very active and were probably responsible for the high efficiency of catalytic system.