[organic] Angel: silicon ether, no longer just a protective group

Aromatic amines are widely used as structural units in bioactive molecules Therefore, it is of great significance to develop new C-N bond construction methods for the synthesis of aniline derivatives Phenol derivatives have rich kinds of protecting groups and reaction activities They can be used as substitutes of halogenated aromatic hydrocarbons and electrophilic reagents for coupling reaction, so as to synthesize aromatic amines For example, wenkert used nickel to catalyze the activation of C-O bond to realize the coupling reaction between aryl methyl ether and amines (j.am.chem.soc 1979, 101, 2246) (scheme1b) However, arylsilyl ethers are rarely used as electrophilic reagents in coupling reactions Because of the stability of the protecting group and its subsequent transformation, it is attractive to develop a new type of coupling reaction (source: angelw Chem Int ed.) recently, the research group of Professor John Montgomery of the University of Michigan developed a new type of amination reaction of arylsilyl Ether Catalyzed by nickel The reaction substrate has a wide range and can realize the coupling of a variety of amines, including aliphatic primary amines, with aryl silicone ethers, providing a new method (scheme1b and C) for the synthesis of aromatic amines At the same time, the selective activation of aryl methyl ether and silyl ether catalyzed by nickel and regulated by ligands has been developed The related research results were published in angelw Chem Int ed (DOI: 10.1002 / anie 201806790) Firstly, the reaction conditions were screened by using morpholine and dimethyl tert butyl siloxy substituted biphenyls as substrates (table S1) Through the screening of a series of electron rich phosphine ligands and nitrogen heterocyclic carbene ligands, the author found that the yield of amination products was 93% with iprme as the ligand In addition, the yield of aryl electrophilic reagents derived from phenol such as anisole and aryl halides (BR, f) can only be low under this condition (source: angelw Chem Int ed.) after optimization of reaction conditions, the author investigated the application range of amine substrates (Table 1) Morpholine, piperazine or piperidine can all react with aryl silicone ether The increase of steric hindrance of amines will decrease the yield of the reaction First or second-order aniline derivatives and aliphatic primary amines can also obtain corresponding target products in medium to excellent yields However, in the amination of aryl methyl ether previously reported, it is difficult for aliphatic primary amines to couple with the corresponding methyl ether (source: angelw Chem Int ed.) next, the author investigated the applicable reaction of arylsilyl ether substrate (Table 2) 1-naphthyl, 2-naphthyl and a variety of heterocyclic (such as quinoline, pyridine, carbazole) substituted silica ethers are compatible under the reaction conditions The reaction can tolerate some common amino and hydroxyl protecting groups, such as BOC and methoxy; unprotected amides can also react smoothly In addition, the estradiol derivative containing alkylsilyl ether can also be coupled with piperidine to obtain the target product 16 It should be noted that in the previously reported nickel catalyzed coupling reaction of aryl methyl ether, the substrate must contain naphthalene type large conjugated aromatic ring structure (source: angelw Chem Int ed.) in view of the good tolerance of the reaction to aryl methyl ether, the author considers the selective activation of aryl methyl ether or silicon ether by controlling the reaction conditions In the orthogonal coupling experiment with 17 as the substrate, the selective and sequential amination and alkylation of silica ether and methyl ether in the molecule were realized by ligand regulation, and the compound 20 (scheme 2) was synthesized by the same route (source: angelw Chem Int ed.) finally, the author studied the sequential coupling reaction of aryl compounds containing various functional groups (scheme3) Taking compound 21 as the substrate, the target product 28 was obtained by methylation, palladium catalyzed Suzuki coupling, nickel catalyzed alkylation of aryl methyl ether and nickel catalyzed ammoniation of aryl silicon ether This result fully confirmed the controllability of the new method and its potential in the late modification of compounds (source: angelw Chem Int ed.) conclusion: Professor John Montgomery, University of Michigan, US, has realized the rapid synthesis of aromatic amines through the amination of aryl silicone Ether Catalyzed by nickel This reaction can selectively activate silicone ether and methyl ether through the regulation of ligands, providing a new method for the construction and post modification of complex compounds