Study group of Zhu Chen, Professor of Suzhou University, reported the long-range C (SP3) - h-linked heteroarylation of alcohol without metal participation

The author of the paper: Professor Zhu Chen's research group has a wide range of compounds with inactive C (SP 3) - H bond in nature It is one of the goals that chemists pursue to directly convert them into valuable chemicals In the past few decades, controlled free radical reactions have gradually become a powerful tool to activate specific C (SP 3) - H bonds, and the reactions can complement the traditional transition metal catalysis Heteroaryl group is one of the most important functional groups in drugs and bioactive molecules Minisci type functional group reaction provides an efficient way to introduce heteroaryl group into complex molecules In this context, Zhu Chen, a professor of Suzhou University who is devoted to the study of alkoxy radicals, has specifically realized the heteroaromatization of C (SP 3) - H bond by alcohol The related achievements were published in nature C communications (DOI: 10.1038 / s41467-018-05522-9) under the title of "metal freealcohol-directed regioselective catalysis of remote deactivated C (SP 3) - hbonds" 。 The O-H bond dissociation energy of alcohol is high (BDE is about 105kcal / mol), so it is very challenging to directly convert alcohol to alkoxy radicals However, the traditional transformation method is to agglomerate alcohol by indirect way Fig 1 The indirect pathway of alcohol to alkoxy radicals (source: angelw Chem Int ed.) not long ago, the research group directly produced highly active alkoxy radicals by using tertiary alcohols under mild reaction conditions, and then a continuous 1, 5-hydrogen transfer and long-range heteroaryl transfer have successfully realized the regioselective heteroarylation of inactive C (SP 3) - H bond in the molecule (angelw Chem Int ed 2018, 57, 1640-1644) Fig 2 Regioselective heteroarylation of nonactivated C (SP 3) - H bonds in molecules (source: angelw Chem Int ed.) Based on the above research, the research team shifted to more challenging intermolecular reactions In the primary stage of the project, besides the target product of heteroarylation of C (SP 3) - H bond, there are also many side reactions, such as elimination of C-C bond β, oxidation of alcohol and intramolecular cyclization Inhibition of side reactions is the key to improve the efficiency of the reaction After a large number of reaction conditions selection, the research team found that under the blue LED light, PIFA ([difluoroacetoxy) iodine] benzene) can effectively promote the direct conversion of alcohol to alkoxy radicals, thus obtaining Minisci products The substrate of the reaction has wide applicability, and the first, second and third alcohols can be well compatible in the reaction system The heteroaromatic ring can be quinoline, pyridine, isoquinoline, phenanthridine, acridine, pyrazine, pyrimidine, quinoxaline, 4-quinoxaline and other nitrogen-containing heterocycles In addition The reaction conditions are mild, metal free and easy to operate Heteroaromatization of alcohol specific sites can be realized at room temperature This work has been applied for patent and is expected to be used in pharmaceutical chemistry research The results were published in nature C communications (DOI: 10.1038/s41467-018-05522-9) Figure 3 Investigation of substrate applicability of reaction (source: nature Communications) review of previous reports by Professor Zhu Chen's research group: CBG information interview with Professor Zhu Chen of Suzhou University Study group of Zhu Chen, Professor of Suzhou University, reported the ring opening functional group reaction of small tension naphthenic alcohol promoted by visible light