Studies On Oxidative Cyanation Reactions

Cyano group is an important functional group in organic synthesis, which can be transformed to a variety of other useful functional groups, so cyanation reactions are important tools to access nitriles, cyanohydrin, aminonitriles, ?-amino acids, ?-hydroxy acids, ?-keto acids as well as acyl nitriles, and have been widely used in organic, pharmaceutical, pesticidal, dye, pigment, liquid crystal and high polymer material industries. In oxidative reactions, the same substrate may be oxidized to different products according to the strength of oxidants and reaction system they are in. This thesis focuses on oxidative cyanation reactions, in which four oxidation systems are used to achieve three types of cyanation products having important application value and biological activities. In these cyanation reactions, oxidation systems can convert nucleophilic substrates into electrophilic intermediates and then react with cyanide anion.The first cyanation reaction is about taking use of hypervalent iodine reagents to achieve umpolung of silyl enol ethers which then react with nitriles to synthesize a series of ?-ketonitriles. Reaction conditions such as different kinds and amount of oxidants, temperature, preactivation and reaction time were optimized. Moreover, electronic effects, substitution effects and steric effects of substrates on the reaction were tested in our research. Silyl enol ethers bearing different substituted aromatic rings, heteroaryl-, naphthalene-, cinnamyl- as well as aliphatic moieties, all afforded corresponding cyanation products with regioselectivity. Oxazole can be also produced when changing substrate and solvent. Applications of ?-ketonitrile have been done to synthesize 5-aminopyrazole and 5-aminoisoxazole. Also, a plausible mechanistic pathway was proposed.The second cyanation reaction is about direct oxidative cyanation of tertiary amines promoted by in situ generated hypervalent iodine(III)-CN intermediate to synthesize a series of ?-aminonitriles. In the research, oxidants, additives, temperature, preactivation and reaction time were also screened. After testing electronic, substitution and steric effects of substrates on the reaction, substituted N,N-dimethylaniline derivatives were found to afford corresponding ?-aminonitriles effectively. Furthermore, the system can also be efficiently applied to cyclic amines. The mechanism of this reaction was also discussed. Benzidine was generated in the absence of TMSCN.The third cyanation reaction is about iron-catalyzed sequential reaction of secondary amines with primary alcohols and trimethylsilyl cyanide to afford corresponding ?-aminonitriles in one-pot. Oxidants, catalysts, solvents, temperature, and reaction time were also optimized, and some new cyanation and iodination reaction were found. The scope of secondary amines and alcohols were investigated. Cyclic and acyclic secondary amines, as well as aliphatic and aromatic alcohols all smoothly gave corresponding ?-aminonitriles. Several control experiments were conducted to clarify the mechanism.The fourth cyanation reaction is about aminocyanation of alkenes using hypervalent iodine reagent combined with iodine to achieve a series of cyclic ?-aminonitriles. After investigation of effects of oxidants, solvents, temperature, and reaction time, oxidants and solvents were found to be decisive factors. Different products were got when using different oxidants. The scope of the reaction were also examined. Substrates bearing different substitutions on aromatic ring and alkenes on nitrogen successfully gave desired products, which provide a useful tool for the synthesis of various nitrogen-containing rings.Four green oxidative systems are established by hypervalent iodine reagents and tbutylhydroperoxide in this thesis, which have been used to achieve ?-ketonitriles, ?-aminonitriles and cyclic ?-aminonitriles. These green methods have mild reaction conditions, wide substrate scope and provide a useful tool for the synthesis of various nitrogen-containing compounds.