Zhu Rong Group, Peking University: free radical polarity cross process in hydrogen functionalization of olefins catalyzed by cobalt

It is an important basic conversion process to construct carbon heteroatom bond from alkene via alkyl radical In this context, the first transition metal (such as Mn, Fe, Co, etc.) catalyzed hydrogen functionalization, with its unique mechanism and accompanying selectivity, shows great research value and application potential The common key step in the mechanism of this kind of reaction is the hydrogen atom transfer (HAT) process between metal hydride (LNM − h) and olefin Through one-step or step-by-step process, the alkyl radical intermediate is obtained by following the martensitic regioselectivity Starting from the free radicals, it reacts with various free radical reagents (somophile), including atom transfer reagent, group transfer reagent and electron deficient unsaturated system, so as to realize hydrogen functionalization At the same time, the development bottleneck of the above reactions is very obvious: 1) the scope of application is mainly limited in the reaction with free radical reagents; 2) the selective control means in the free radical capture process is mainly limited in the substrate control In view of the limitation of classical hat reaction, recently, Zhu Rong Group, School of chemistry and molecular engineering, Peking University, proposed the radical polar crossover via alkylco (III) intermediate, which realized the intermolecular hydrogen functionalization reaction with high efficiency and high functional group compatibility Relevant research results were published in J am Chem SOC (J am Chem SOC., 2019, 141, 7250) Introduction to Zhu Rong's special research team Zhu Rong, School of chemistry and molecular engineering, Peking University, was founded in March 2018 His main research interest is to develop new transition metal catalysis process, accurately build organic functional small molecules and polymers, and explore their electrochemical properties and photoelectric response function We sincerely invite young talents to join us (website: http://www.chem.pku.edu.cn/rongzhu/index.htm) Introduction to Zhu Rong, a special researcher, was selected into the youth thousand talents program of the central organization department In 2010, he graduated from Peking University with the guidance of Professor Yang Zhen and Professor Chen Jiahua He then studied the transition metal catalyzed asymmetric free radical bifunctional reaction under the guidance of Professor Stephen Buchwald of MIT, and obtained his Ph.D in 2015 In 2015-2018, research on functional polymers and sensors was conducted under the guidance of Professor Timothy swager of MIT Since March 2018, he has worked in the school of chemistry of Peking University to carry out independent research Zhu Rong's work on asymmetric free radical reaction and chemical sensors has attracted the attention of famous scientific and technological media such as C & en (American Chemical and Chemical News) He was selected as "top research of 2016" by ACS, and won the award of excellent international student of China Scholarship Council Leading scientific achievements: in order to break through the limitation of the classical hat hydrogen functionalization reaction, inspired by the chemistry of alkylco (III) complex, the author proposed that: using the radical polar crossover as hat Intermediate free radicals provide a new reaction pathway with certain universal significance (Fig 1) Figure 1 Free radical polar intermolecular hydrogen functionalization (source: J am Chem SOC.) in the model reaction, the author uses the high valent iodine (III) reagent 7 As the precursor of dielectronic group transfer oxidant and nucleophilic reagent, hydrogen functionalization between molecules was successfully induced, and the addition of o-iodobenzoic acid to non activated olefins was realized at room temperature (Fig 1) Several kinetic data indicating the mechanism were also collected (Fig 2) Among them, the most important ones are: 1) the main reaction and the competitive reaction after the induction period show zero order kinetics to the substrate and the equivalent reagent; 2) the reaction order of the catalyst is 2; 3) the olefin isomerization comes from the reverse hat process of the alkyl radical, and the reaction order of the process to the catalyst is 1; 4 ）The optical purity of the chiral catalyst has a certain influence on the reaction rate, and a weak stereoselectivity can be observed Fig 2 Model reaction study (source: J am Chem SOC.) after completing the work of condition screening, the author inspected the application scope of this catalytic system for olefins and nucleophiles respectively, and focused on the functional compatibility test (see Fig 3 for some examples) For the substrates containing functional groups incompatible with the catalytic conditions of p-protonic acid and Lewis acid, the yield of hydroesterification is better When styrene, 1,3-enyne and vinyl ether were used as substrates, the yield was also ideal The above transformation can also be achieved by mixing PhIO with some acidic nucleophiles in situ It is found that for some potential hydrogen acceptors such as nitro, Michael acceptor, carbonyl and other functional groups, the reaction still has a good yield, and no reduction products have been observed When there are acid sensitive functional groups (such as amines protected by BOC Group and phenols protected by TBS group) in the molecule, the reaction can proceed smoothly, and there is no unprotected product HNTs 2 can be used as nucleophile to synthesize sulfonamide derivatives Figure 3 Some examples of substrate range (source: J am Chem SOC.) based on literature research and kinetic research, the research team proposed a catalytic cycle as shown in the figure below (Figure 4): first, Co − Nu and CO − h species (12, 13) were formed; Co − h species and alkene had reaction, resulting in free radical 15 and alkyl CO (III) complex 14 In equilibrium, Co − Nu species 12 and alkylco (III) complex 14 are likely to undergo a rate dependent bimetallic process to obtain products and regenerate CO (III) Fig 4 Possible catalytic cycle (source: J am Chem SOC.) Fig 5 Inhibition of the formation of alkylco (III) complex (source: J am Chem SOC.) in view of the important role of the proposed alkylco (III) complex 14 in the main reaction, the author blocked the formation of 14 by increasing the temperature and increasing the steric hindrance of free radicals, respectively (Fig 5) The experimental results show that when the formation of 14 is inhibited, the formation of carbon oxygen bond is obviously inhibited, and the isomerization process begins to dominate, which further confirms the mechanism hypothesis This achievement was recently published in J am Chem SOC (J am Chem SOC., 2019, 141, 7250) The author of this paper is Xiao Le Zhou, Fan Yang, Han Li sun, Yun Nian Yin, Wei Ting ye, and Rong Zhu Dr Zhou Xiaole and Dr Yang fan are the same first authors The above research work was supported by Peking University and Beijing National Research Center for molecular science Nowadays, people and scientific research have been paid more and more attention in the economic life China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeangoapp, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research group, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.