DBFOX/Ph-M²⁺ Catalytic Cyanogen Amine With Electron-deficient Olefins In The 1,3-dipolar Cycloaddition Of Stereoselectivity

The 1, 3-dipolar cycloaddition is a very important kind of reaction in organic synthesis, is five yuan pyrazole Lin heterocyclic synthesis methods.Pyrazole Lin heterocyclic structure exists in many drugs, is a mother with a variety of bioactive compounds, pyrazole, the synthesis of heterocyclic derivatives play an important role in the field of organic.Two coumarone double oxazoline ligands(DBFOX) since the discovery, has good catalytic stereoselectivity, improve the catalytic rate and a series of advantages.Is widely used in three-dimensional selective ring opening reaction, Michael addition, alpha a substitution reaction,Diels-Alder, and the 1,3-dipolar cycloaddition of study.Based on the synthesis of these compounds is complex, harsh reaction conditions such as problem, this paper, by using the improved method for synthesis of DBFOX/Ph, and studied the cyanogen amine with electron-deficient olefins 1, 3-dipolar cycloaddition.Taking two coumarone as starting materials, the synthesis of diphenyl and furan type catalyst, c2-symmetric chiral bis(oxazoline)and catalytic cyanogen amine with electron-deficient olefins of N-alpha, beta unsaturated acyl-3,5-dimethyl pyrazole specific content is as follows:1.The synthesis of DBFOX/Ph: through halogenated, nucleophilic substitution, condensation cyclization three-step reaction preparation of diphenyl and furan base pairs of oxazoline ligands(DBFOX/Ph).In coumarone as raw material, reaction with n-butyl lithium generate lithium, lithium and iodine elemental electrophilic substitution reaction, generation of 4,6-2 iodine generation 2 coumarone, yield was 55.7%.4, 6-2 iodine generation 2 coumarone with cuprous cyanide nucleophilic substitution reaction, generation of 4, 6-2cyano 2 coumarone, yield was 66.6%.Finally ammonia alcohol with L- aniline ring also DBFOX/Ph, yield of 45.0%;2. Series 1 benzoyl phenyl hydrazone derivatives synthesis: with benzoyl chloride as raw material, under the catalysis of pyridine, and phenylhydrazine hydrochloride reaction yield was 80.0%.In acetonitrile solvent, under the catalysis of triphenylphosphine and reaction with carbon tetrachloride chlorinated,benzoyl chlorobenzene was hydrazone, yield was 50.0%;3. With anhydrous Li Cl as catalysts, triethylamine HCL agent, was synthesized at room temperature close dipole body N- propylene acyl-3,5-dimethyl pyrazole and N-butene acyl-3,5- dimethyl pyrazole, the introduction of the method with catalyst anhydrous Li Cl, 6 times shortening reaction time is a literature method, the yield increased by 50%, to 90%.4. 1. The 1,3-dipolar cycloaddition of catalytic reaction research: finished with benzoyl chlorobenzene hydrazone and electron-deficient olefins 1, 3-dipolar cycloaddition research, mainly studies the reaction temperature, catalyst dosage,different alkali and lewis acid the yield of the reaction, the influence of the reaction of stereoselectivity.The experimental results show that under 0 ?,activation of 4 ams, 10% mol DBFOX/Ph-Ni catalyst, i-Pr2 NEt as alkali, the reaction to produce five product is given priority to, the reaction yield is more than 90%, selective ee value of 95%.Based on this, explores the four kinds of cyanide imide derivatives and two electron-deficient olefins(N-propylene acyl-3,5-dimethyl pyrazole and N-butene acyl-3,5-dimethyl pyrazole) reaction catalytic effect.The results showed that the catalytic product ee value reaches 60-90%.