Wang Chuan, Professor, University of science and technology of China, project team: alkylation of nonactivated olefins by series reaction of migration insertion / decarboxylation coupling under the catalysis of nickel

The author: Professor Wang Chuan's group is one of the most important reactions in the field of organic synthesis In recent years, PD, Ni, Cu and other transition metals have been used as catalysts to realize the double carbonization of non activated olefins through the strategies of "oxidation-reduction neutral" and "reducibility", respectively In 2014, Gregory C Fu team first reported the asymmetric alkylation of nonactivated olefins catalyzed by nickel However, borane needs to be used in this reaction, which makes the synthesis of substrates more difficult and the tolerance of functional groups is not high If halide is used as the starting material directly, the above problems can be effectively avoided by reduction strategy Professor Wang Chuan's research group of University of science and technology of China has been devoted to the methodology research of reductive nickel catalyzed electrophilic functionalization of olefins In 2019, Wang Chuan group used alkyl bromide as alkylation reagent to realize the aryl alkylation of non activated olefins catalyzed by reductive nickel (chem SCI., 2019, 10, 1780; angel Chem Int ed., 2019, 58, 6722) Compared with halogenated compounds, carboxylic acids have the advantages of stability, low toxicity and direct access to nature On the basis of the previous work, the group developed the aryl alkylation of non activated olefins with active esters as alkylating agents, with the participation of nickel metal Relevant research results were recently published in the Journal of org Lett (DOI: 10.1021/acs.orglett 9b02870) First of all, the author tried to use the aryl iodide 1A with 1,1-disubstituted alkenes and the active ester 2A derived from nonanoic acid (Table 1), and established the optimal reaction conditions (entry 1) In addition, the author found that the target product could not be obtained when aryl bromide was used Next, we found that L1 was the best ligand when we used different ligands Then the author screened the common solvents and found that the effect was not ideal when DMA and NMP were used If manganese powder is used instead of zinc powder as reducing agent, the yield will be reduced When zinc iodide is not used or when the temperature is raised or cooled, the yield will be reduced (source: org Lett.) then, the author expanded the substrate (scheme 2) The medium and higher yield (3a - 3e) can be obtained by using the active esters derived from different alkyl carboxylic acids It is worth noting that when the alkyl chain is linked with aromatic ring or indole ring, the reaction can still be carried out and a medium yield (3f - 3I) can be obtained The higher yield (3j - 3L) can also be obtained by using substrates with different functional groups (such as ester, carbonyl, amide) It is worth noting that the target product (3m - 3O) can also be obtained when the active ester with alkyl chloride, alkyl bromide and hydroxyl is used Compared with the previous work, the active ester can be used as alkylation reagent (3P - 3S) of secondary carbon In the end, the author expanded the substrates of different non activated olefins, and obtained medium or higher yield (3T - 3Al) (source: org Lett.) and then the author studied the mechanism of the reaction It was found that when zero valent nickel was used, olefins could react to produce four products (Table 2) In this paper, the equivalency experiment of bivalent nickel / zinc powder and zero valent nickel was carried out The ratio of the four products was detected by GC-FID It was found that the reaction was initiated by the oxidation addition of zero valent nickel to aryl iodine At the same time, the author found that zinc iodide can promote the reaction obviously (source: org Lett.) finally, the asymmetric reaction was studied by using chiral oxazoline ligands It was found that a good yield of asymmetric induced product (scheme 5) could be obtained by using ligand L6 (source: org Lett.) Summary: Professor Wang Chuan's research group has developed a nickel catalyzed aryl alkylation of active esters with inactive olefins The reaction not only has a wide range of substrate applications, but also provides a new idea and method for the bifunctional reaction of olefins catalyzed by nickel under reduction strategy The article was recently published on org Lett The first author of the article is Jin Youxiang, a doctoral student at the University of science and technology of China, and the corresponding author is Professor Wang Chuan.