C−H Activation – Far from Over

Abstract

“Some people are thinking that the research field of C−H activation is already saturated and there is some truth to their conclusion. Many research groups are now involved in studies focusing on C−H activation. […] However, there are many problems that still need to be solved.” Editorial Board member and guest editor Naoto Chatani shares his views on the history and current status of C−H activation. Chemical reactions are the consequence of bond cleavage and bond formation. In terms of bond cleavage, a wide range of reactive chemical bonds, which are referred to as functional groups, can be used as starting materials. In this sense, the use of reactive chemical bonds in organic synthesis has long focused on aspects of molecular transformations. In fact, this is obvious when one reads a textbook of organic chemistry. Most organic chemistry textbooks are segregated by functional groups. In this context, C−H bonds have not been recognized as a functional group. In 1955, Murahashi reported a Co2(CO)8-catalyzed cyclocarbonylation of aromatic imines, in which the ortho C−H bond was carbonylated (J. Am. Chem. Soc. 1955, 77, 6403). This represents a pioneering example of not only chelation-assisted C−H bond activation, but also of the use of a cobalt complex as a catalyst in C−H functionalization reactions. However, unfortunately, this work had not received the attention it deserved because the chemistry community failed to notice the importance of this work at the time it appeared. Appropriate terminology, such as C−H bond activation did not exist back then. In fact, more than half of studies that cited this paper were studies that were done after 2014. In 1967, Fujiwara and Moritani reported a PdII-mediated dehydrogenative coupling reaction between benzene and styrene, leading to the production of 1,2-diphenylethlene (Tetrahedron Lett. 1967, 8, 1119). They subsequently succeeded in developing this into a catalytic reaction. However, this reaction could not overcome the issue of regioselectivity, which is an important and fundamental issue to be addressed in the sense of organic synthesis. The development of C−H bonds in organic synthesis had to wait until Murai's seminal paper. In 1993, Murai reported a Ru-catalyzed C−H alkylation of aromatic ketones with alkenes, in which the alkylation took place exclusively at the ortho-position (Nature 1993, 366, 529). The coordination of a ketone oxygen to the ruthenium center, leading to the generation of five-membered metalacycle, is the key step for the success of this reaction. By taking advantage of chelation assistance, this methodology has now been extended to not only a wide variety of directing groups, but also various C−H functionalization reactions. All of these seminal works mentioned above were developed in Japan. This would be the right time to publish a special issue in Asian J. Org. Chem., because the 4th International Symposium on C−H Activation (ISCHA4) will be held in Yokohama, Japan, this August. The editors, and guest editors Naoto Chatani and Jin-Quan Yu, wish to thank all of the authors for their contributions to this special issue and for making this project a truly successful one. Some people are thinking that the research field of C−H activation is already saturated and there is some truth to their conclusion. Many research groups are now involved in studies focusing on C−H activation. We now see many papers related to C−H activation in every issue of even higher-impact journals. However, there are many problems that still need to be solved. We are still unable to control the regioselectivity of such reactions to the extent that we wish. The reaction is still substrate-controlled. The direct functionalization of simple alkanes, especially that of methane, is important, since it is related to the effective utilization of natural resources. Catalytic reactions involving a C−H bond and other unreactive bonds, such as C−O, C−N, and related bonds, promise to be the next target reactions that need to be developed. Our hopes are that this special issue will serve as a source of stimulation for further developing a research field that was originally developed in Asia. Prof. Naoto Chatani Guest Editor and Editorial Board Member