Transition Metal Catalyzed "Borrowing-cyanide" Strategy In Organic Synthesis Reactions

Cyano groups are more common in organic compounds.Many natural products and drug molecules have cyano groups.At the same time,cyano groups can also be derived from many important organic chemical materials and biologically active compounds such as carboxylic acids and amides.,aldehydes,ketones and amino acids,etc.In recent years,green and efficient cyanochemistry has attracted widespread attention from many chemists.Hydrocyanation and transfer hydrocyanation as the traditional cyano reaction play a major role in cyanochemistry.Recently,cyanochemistry has continuously proposed new reaction types,in which hydrocyanation of α,β-unsaturated compounds,cyano participation The research on the reaction of difunctionalization and various forms of Strecker reaction is relatively thorough.However,whether it is hydrocyanation or transfer hydrocyanation,the atomic economy is not high and the toxicity is still high.Considering the requirements of green and efficient chemical reactions,we want to study a high-atom,low-toxicity cyanation reaction.Therefore,we envisage that the cyano group is slowly released in the reaction system by using cyanohydrin as a cyanogen source.The resulting ketone or aldehyde is used as a substrate for the next reaction,avoiding the waste of atoms and improving the economics of the atom;in the reaction,the cyano group is temporarily stored on the metal,and the metal is cyanide after the ketone or aldehyde is formed in the next reaction.The base also returns to the formation of intermediate compounds,avoiding the presence of cyano groups in the form of highly toxic anions or hydrocyanic acid,which solves the problem of high toxicity in the reaction system;in addition,the by-product in the entire reaction system is water and is environmentally friendly.High degree,in line with the development requirements of green chemistry.This kind of reaction to the cyano group has the principle of "borrowing and returning",which is called "borrowing-cyanide" reaction.This paper mainly studies the reaction of "borrowing-cyanide" from two aspects:Part I:The nickel-catalyzed cyanohydrin reacts with the aldehyde(ketone)to synthesize the corresponding cyano cyano ketone.Under the action of nickel and phosphine ligands,the cyano group in the cyanohydrin is first pinned on the nickel,releasing the corresponding ketone or aldehyde,and then reacting with another aldehyde(ketone)under the action of a base to form an Aldol reaction.The ketene,the final cyano Michael addition,efficiently synthesized the corresponding β-cyano ketone compound and proposed the "borrowing-cyanide" reaction strategy for the first time.The reaction is efficiently earried out in a yield of 82%.The substrate of the reaction is widely applicable,and the cyanohydrin can be reacted well with various aromatic aldehydes,heteroaromatic aldehydes and fatty aldehydes.It is worth noting that the cyanohydrin of aldehyde can also participate in this kind of "borrowing-cyanide"reaction,and the feasibility of our "borrowing-cyanide" reaction strategy is proved by experiments.Part II:Direct amination of cyanohydrins by titanium catalyzed by a"borrowing-cyanide" strategy.Under the catalysis of titanium,the cyanohydrin elimination reaction produces a corresponding carbonyl compound and the amine is condensed into an imine,and a Strecker reaction occurs to efficiently synthesize a a-amino nitrile compound.At the same time,we also tried the catalytic asymmetric mode of this reaction.Under the action of Ti(Oi-Pr)4,quinine and chiral BINOL,the corresponding chiral products can be obtained with high efficiency and high stereoselectivity,up to 87%ee.In this reaction,the substrate has a wide range of applications,and various ketone cyanohydrins,aldehyde cyanohydrins and amine compounds can participate in this "borrowing-cyanide" amination reaction.