The Halogen Bonding Activated N-haloimide And Alkyne Initiated Halogenation/Aminohalogenation/Oxo-amination Reaction

Halogen bond is an intermolecular weak interaction which is similar hydrogen bond. It is formed by halogen atoms (Cl, Br, I) as an electron acceptor, and Lewis base. So far, the halogen bond has been widely used in crystal engineering, materials science, molecular recognition and biological systems and drug design. However, the halogen bond has not been universally used in organic synthesis by now. On the basis of the early stage of the research work, this paper explores the organic synthesis in which halogen bond is applied.This thesis mainly studys that by the activation of halogen bond, the electrophilic ability of halogen ion and nuclear capability of imide anion are effectively improved. The halogenation, aminohalogennation and oxo-amination reaction of alkyne have been effectivelyachieved through the activation of halogen bond. Met hods adopted in this thesis have several advantages, such as mild conditions, readily available reagents and atom-economy.The thesis can be divided into six chapters. The first chapter summarizes the definition of halogen bond; The application of halogen bond in organic synthesis reaction; some cases of N-haloimide which serves as halogenation reagent, amination reagent, haloamination reagent, and oxidant reagent in organic reactions.The second chapter puts forward the bases of this thesis.Chapter three, Directly from terminal alkynes and with N-halosuccinimides (halo= Br and I) or N-cholorophthalimide as the halogen sources, DBU as the activator,1-haloalkynes were prepared in good to excellent yields at room temperature. Bis(bromoalkyne) and bis(iodoalkyne) were also synthesized in excellent yields with the NBS(NIS)/DBU combination. The reaction features inexpensive and readily available reagents, mild conditions, simple execution, extremely short reaction time, broad halogen scope. Compared to the literature reported methods, our synthetic strategy provided a greener approach towards 1-haloalkynes.Chapter four:Activated by DBU, N-haloimides can be used as both halogen and nitrogen sources to achieve the difunctionalization of terminal alkynes, giving rise to useful halogenated enamines with high efficiency and high regio- and stereoselectivities. The cascade reaction features simple manipulation, mild conditions, a broad substrate scope, and atom-economy.Chapter five we have developed a simple, one-pot, two-step cascade reaction towards ?-amino ketones has been developed. Both terminal and internal alkynes react with DMF-activated N-bromosuccinimide (phthalimide) and water (as external O-nucleophile), followed by the addition of DBU, giving imidated ketones efficiently (the N-sources arises from N-haloimide itself). The formation of mono and/or diamino ketones depends on whether NBS or NBP is utilized. A mechanism of sequential oxy-1,1-dibromogenation of alkynes, nucleophilic substitution and reductive debromination (or second nucleophilic substitution) was proposed.In chapter six:Direct a-amination of nitrones has been developed by using N-haloimide-DBU protocol. It was found that the E- and Z-isomerization in the a-aminonitrone products is sensitive to acidic substances like silica gel and Br(?)nsted acid. In addition to nitrones, quinoline N-oxides are also suitable substrtaes. The reaction features mild conditions, broad substrate scope, inexpensive and readily available reagents, high efficiency, and metal-free.