Bifunctional reaction of non activated olefins catalyzed by JACS: Ni

For a long time, using the first line of transition metals to achieve some challenging C-C bonding is one of the goals that chemists have been pursuing In particular, Ni catalyzed C-C bonding has attracted a large number of chemists' efforts, which is mainly due to the low cost of Ni and its particularity compared with PD These characteristics prompted chemists to develop many useful strategies and synthesize many useful compounds Among these methods, the 1,2-difunctional reaction of non activated olefins is a powerful synthesis strategy to construct two C-C bonds at the same time Despite the rapid development of Ni catalyzed C-C bonding, the olefin functionalization with heterocyclic structure is still a great challenge, which is mainly due to the strong coordination of heterocyclic compounds with Ni, leading to deactivation of the catalyst However, the development of the bifunctional reaction of olefins with heterocyclic structure has certain value for the synthesis of active molecules of drugs Among them, the olefin bifunctional reactions initiated by electrophilic reagents have developed completely Recently, the reduction strategy has been used to realize the olefin bifunctional reactions of two electrophilic reagents In contrast, the first line of transition metal catalyzed olefin bifunctional reactions initiated by nucleophiles have been less developed In this respect, Fu group reported the stereoselective cyclization and alkylation reaction initiated by aryl-9-bbn; brown group reported the cyclization and arylation reaction initiated by arylboric acid; giri group realized the free radical cyclization and arylation reaction catalyzed by Cu by aryl or alkylzinc reagent (Figure 1a) However, the use of enols to initiate olefin bifunctional reactions is limited to the use of Pd catalysts Despite these advances, the use of unstable enols to initiate olefin bifunctionalization has not been reported In the conia ene reaction, the use of unstable enols can achieve the monofunctionalization of non activated olefins, but it needs high temperature conditions, and the tolerance of functional groups is very poor The further development of the catalyst has realized the α - alkylation of the unstable enols, but the bifunctionalization of alkenes has not been realized Recently, the Timothy R Newhouse group of Yale University has realized the bifunctional reaction of non activated olefins catalyzed by Ni using the non stable enols, in which the electrophilic agents can be aryl, alkenyl and amino structures Relevant research results were published in J am Chem SOC (DOI: 10.1021 / JACS 9b09245) (source: J am Chem SOC.) the author first used 1a and 2-chloropyridine as template substrate for condition optimization (Table 1) Through the optimization of the reaction conditions such as ligands and additives, the following conclusions are obtained: the monodentate ligands are more favorable for the reaction; the lithium salt as additives will inhibit the reaction; when the aromatic heterocyclic halogens are used as electrophilic reagents, tbaotf is very important for the smooth progress of the reaction At last, the optimal reaction conditions are as follows: NiCl2 (DME) is the catalyst precursor, P (p-cf3-c6h4) 3 is the ligand, Zn (TMP) 2 is the base, TBAI is the additive, the substrate reacts in 1,4-dioxane / THF mixed solvent at 80 ℃ for 12 hours, and finally the target product is obtained with 80% separation yield (source: J am Chem SOC.) after determining the optimal reaction conditions, the author expanded the substrate range of the reaction (Table 2) Firstly, the leaving group of aromatic halogenated compounds was investigated It was found that the target product could be obtained by similar reaction efficiency of aromatic iodide, bromine, chlorine and aromatic OTF Among them, the electrical properties of chlorinated compounds have no effect on the reaction Subsequently, the compatibility of functional groups was investigated and it was found that ketone structure, CN and F were compatible with reaction conditions For structures such as 4-chloroiodobenzene, the reaction tends to take place on iodine; for 4-chlorophenylethylene, there is no functional product of activated olefin Finally, the author investigated the substrates of aromatic heterocyclic halogenated compounds, and found that some of them were compatible with the reaction conditions Importantly, alkenyl bromide, alkenyl OTF, alkenyl iodine and "n-obz" can also participate in the reaction (source: J am Chem SOC.) finally, the author made a preliminary study on the reaction mechanism, and speculated that the reaction formed alkyl zinc species, and obtained the target product through the subsequent single electron transfer process, but did not exclude the Ni catalyzed transfer insertion reaction mechanism Summary: Timothy R Newhouse group reported for the first time the Ni catalyzed bifunctional reaction of inactive olefins The reaction was initiated by an unstable enol, which can be used for the efficient synthesis of many bicycles, providing an enlightening method for the complex synthesis of compounds.