Study On Cyanation Wih α,β-Unsaturated Carbonyl Compounds As Substrates

As a vital organic functional group,the cyano group widely exists in many natu-ral products,medicines and other fine chemicals.The most direct way to introduce cyano groups into molecules is through the conjugate cyanation ofα,β-unsaturated carbonyl compounds.Theβ-cyano ketone generated by the reaction is a significant class of organic synthesis intermediates,which is a crucial raw material to synthesize amino acids,especially the optically activeβ-cyano ketone can convert intoγ-aminobutyric acid（GABA）.In addition,cyano groups can be converted into amides,amines,carboxylic acids and their derivatives,aldehydes,ketones,alcohols,nitro-gen-containing heterocycles,etc.Therefore,it is of great significance to deeply study the cyanation ofα,β-unsaturated carbonyl compounds.The specific research contents of this paper are as follows:1.Conjugate cyanation ofα,β-unsaturated ketone.Using acetone cyanohydrin as the cyanogen source andα,β-unsaturated ketone as the substrate,the efficient prepa-ration ofβ-cyano ketone was realized.Taking the conjugate cynation of chalcone as a model,the influence factors such as the type and amount of base,temperature,sol-vent,and the amount of acetone cyanohydrin on the reaction were investigated,re-spectively,and the optimal experimental conditions were determined:Li OH·H₂O was used as the base,the molar ratio of the reaction substrate,acetone cyanohydrin,and Li OH·H₂O was 1:2.5:1.6,DMF and H₂O in a volume ratio of 4:1 were used as the solvent,and the reaction temperature was 60°C.Under the optimal conditions,the highest yield ofβ-cyano ketone could reach 98%.Further investigation of the scope of substrate application showed that 16 chalcone derivatives could obtain the corre-spondingβ-cyano ketone products in 85%～98%yields.2.Synthesis of chiral ligands.Two chiral ligands,L1 and L2,which were based on the structure of binaphthol,were synthesized by（R）-binaphthol and（S）-binaphthol as raw materials,respectively.Staring from malononitrile,diethyl ami-nomalonate was prepared,and then condensed with chiral amionoindanol and and L-phenylglycinol to generate intermediates L3 and L11.Seven kinds of chiral bisoxa-zolines L4～L10 were obtained from L3 and two kinds of chiral bisoxazolines L12～L13were obtained from L11.3.Asymmetric conjugation cynation of 3,5-dimethylacylpyrazole.Taking the conjugate cyanation reaction of 3,5-dimethyl-N-α,β-unsaturated acylpyrazole and acetone cyanohydrin as a model,the optimum reaction conditions were established by investigating the effects of chiral ligand,coordination metal,catalyst dosage,ratio of ligand to metal,solvent and temperature on asymmetric conjugate cyanation:.When the complex formed by 20 mol%of bisoxazoline ligand L7 and dibutylmagne-sium（1:1）was used as catalyst,1,2-dichloroethane was used as solvent,and the reac-tion temperature was-18°C,the reaction effect was the best,the product’s yield was87%,and the er value was 86:14.The scope of substrates was further investigated,and the results showed that 12 kinds of cinnamyl pyrazole derivatives and acetone cyanohydrin could obtain the target products with the yield of 77%～88%and the er value of 60:40-79:21.When trimethylsilyl cyanide was used as cyanide source,this catalytic condition was also suitable,and 13 cinnamo pyrazole derivatives could be converted to target products in 75%～91%yield and 58:42～91:9 er value.