[organic] direct cyanidation of C-H bonds of olefins without metal participation reported by the research group of armido student, University of Minster, Germany

Cyano groups are widely found in natural products, drugs, agricultural chemicals and polymer molecules, and can be used as precursors for the synthesis of primary amines, tetrazoles, aldehydes and ketones Aryl cyanogens are usually prepared by cyanidation of aryl halides, pseudo halides and diazonium salts In recent years, guided group assisted transition metal catalyzed C-H bond activation also provides a more simple and atom economical method for the synthesis of aryl cyanogens However, the study of direct cyanidation of C-H bonds of olefins is still rare Recently, the armido student group at the University of Minster in Germany reported for the first time a direct cyanidation (scheme 1) of C-H bond of olefins without metal participation The in-situ aryl (dicyanodiiod) (III) was used as the C-H bond activator and cyanogen source of olefins The reaction has a wide range of substrate application and good non enantioselectivity The research results were published in the international authoritative journal angel Chem Int ed (DOI: 10.1002 / anie 201807303) (source: angelw Chem Int ed.) firstly, the author selected the reaction conditions with α - phenylstyrene 1A as the substrate (Figure 1 and table 1) Most of the cyanogens or oxidants can only make the reaction obtain the target product in trace yield At 40 ℃, 5.5 equivalent 2K as cyanogen source, 1.5 equivalent 3D as oxidant, 1.5 equivalent TMSOTf as additive can promote the reaction to proceed smoothly, and the target compound 4A can be obtained in 90% yield (source: angelw Chem Int ed.) (source: angelw Chem Int ed.) after obtaining the optimal reaction conditions, the author studied the substrate applicability of olefins (Table 2) α - methylstyrene substituted by electron donor or electron acceptor can obtain the corresponding target product in medium to good yield Generally speaking, the electron absorption group is unfavorable for obtaining high e-alkenes Naphthalene ethylene or cyclohexyl and isopropyl substituted styrene with large steric hindrance can also react β - methylstyrene, 1,2-stilbene and trisubstituted styrene are all suitable substrates Moreover, in the gram scale, the product 4A can still be obtained in 91% yield in 1a, which proves that the reaction has the scalability (source: angel Chem Int ed.) in addition, we found that the product 4q (Z / E = 1.2:1) can enrich the z-isomer in the presence of ultraviolet light and (-) - vitamin B2 (Z / E = 17:1), while the product e-4q can reverse the configuration to obtain z-4q (z / E = 20:1) This fully shows that the method has the potential to prepare a single configuration of ethylene cyanogens (scheme 2) (source: angelw Chem Int ed.) in order to clarify the reaction mechanism, the author made a very detailed control experiment (scheme 3) First of all, the free radical probe 1y was added into the reaction system, and no ring opening product 5 was detected, which indicated that the reaction did not go through the free radical mechanism (scheme 3a) In the absence of Lewis acid, the reaction can not take place, which shows the necessity of TMSOTf In the absence of TMSOTf, 4 a can also be obtained in 87% yield by ARI (CN) OTF 2H and tmscn, indicating that ARI (CN) OTF may be a scheme 3b, which was obtained in situ by TMSOTf and 3D In addition, the target product could not be obtained by using ARI (CN) OTF for 2h alone, indicating the importance of tmscn Other nucleophilic CN reagents, such as NaCN, KCN, (n-Bu) 4 NCN, can not replace tmscn to provide cyanogen source, which further explains the necessity of TMS group (scheme 3C) PH 2 IOTF is not competent for oxidant (scheme 3e) These results fully show that it is possible to form dicyanoaryl iodide by in situ reaction between tmscn and 2H Finally, the reversibility of trivalent iodine reagent activation and the slow fracture of C-H bond (scheme 3f-g) are further explained by kinetic isotope effect experiment (KIE) (source: angelw Chem Int ed.) conclusion: the research group of armido student, University of Minster, Germany, reported for the first time a direct cyanidation of olefin C-H bond without metal participation 1,1-disubstituted, 1,2-disubstituted and trisubstituted olefins can all undergo cyanidation successfully, which has a wide range of substrate applicability and good non enantioselectivity.