Metal-Free Direct C(sp~3)-H Cyanide Reaction

Cyano is an important basic element in natural products,drugs,functional materials,agrochemicals,and has an important position in synthetic chemistry.It plays an important role in synthetic chemistry.The corresponding aldehydes,acids,alcohols,amides,and ketones can be obtained by cyano groups.The direct C(sp~3)-H cyanation reaction provides a simple,high-efficiency,atomic and economical method for obtaining nitriles,and represents an important research direction in this field,while the C(sp~3)-H bonds of inert substrates are directly activation and functionalization is very important for chemical synthesis and industrial applications.In the past few decades,most of the methods for achieving the carbon-hydrogen bond activation required expensive transition metal catalysts.With the continuous improvement of research methods,the transition from noble metals to non-precious metals has been realized.Due to the high bond energies and weak coordination properties of C(sp~3)-H bonds,there have been few reports on the direct activation and functionalization of metal-free C(sp~3)-H bonds.Therefore,it is also challenging to realize the metal-free C(sp~3)-H bond functionalization.The hypervalent iodine(?)compounds have attracted great interest from organic researchers due to their high reactivity,strong oxidation properties,excellent selectivity,low toxicity,good environmental characteristics,and commercial availability.In recent years,the hypervalent iodine(III)reagents has also been widely used in cyanation reactions.However,there has been no report of direct C(sp~3)-H cyanation reactions using hypervalent iodine(III)cyano reagents for inert alkane substrates.The main contents of this study are as follows:(1)Under the condition of metal-free catalysis,the direct C(sp~3)-H cyanation reaction of alkanes,ethers and tertiary amine substrates was achieved through the selection and optimization of a series of conditions such as catalysts,cyano reagents and oxidants and other conditions.This paper uses hypervalent iodine(III)reagents,low toxicity and high-activity,can be used as a cyanide reagent and as an oxidant.Under the initiation of tert-butyl peroxide(TBPB)and no metal catalyst exists,the direct C(sp~3)-H cyanidation reaction of the inert substrate alkanes,ether and tertiary amine substrates was realized.(2)The reaction mechanism has been studied in depth.The experimental results show that the reaction process belongs to two different reaction systems:The reaction mechanism of alkanes and ether substrates indicates that the reaction process involves a free radical mechanism;the tertiary amine substrates mechanism studies indicate that the reaction process involves the oxidation of cyanide.The reaction conditions of the two different reaction systems of the direct C(sp~3)-H cyanation reaction developed by us are relatively mild,do not require metal catalysis,the reaction process is relatively green,the applicability of the substrate is also relatively wide,and functional groups are well tolerated with yields up to 98%.The reaction system provides alternative methods for synthesizing alkanenitriles,?-aminonitriles and the like.