ACS catalyst: Zhao Dongbing's research team of Nankai University realized C (SP3) - H bond arylation / amidation of silylmethyl

Organosilicon compounds are widely used in organic chemistry, material science and pharmaceutical chemistry They are useful reagents for the construction of some important molecular skeletons In recent years, C-H functionalization of silane methyl has provided a simple and effective way to synthesize a variety of organosilanes The C-H boration and intramolecular arylation of silyl methyl have been reported Due to the advantages of easy installation and removal of silicon chains, the functionalization of C (SP 2) - h has made great progress (Figure 2C), however, there is no report on the functionalization of C (SP 3) - H Recently, Zhao Dongbing's team of researchers at Nankai University successfully developed the first case of C-H bond arylation / amidation of silyl methyl catalyzed by IR III / Rh III (Figure 2e) Relevant research results were published on acsacatal (DOI: 10.1021 / acscalal 9b00771) (source: ACS catalyst.) at first, the activity of C-H bond arylation of alkanes was investigated with 2 - (tert butyl Dimethylsilyl) pyridine 1a and phenyl (m-trimethylphenyl) iodonium trifluoromethylsulfonate 2A as model substrates After extensive screening of various conditions, such as different aromatic sources, catalysts, additives, bases and solvents, the author determined that the optimal conditions for the reaction were as follows: 5 mol% of [(Cp * ircl2) 2] as the pre catalyst, agntf 2 as the halogen extraction reagent, csoac (1.0 equivalent) and 4 Å MS as the additives, cyclohexane as the solvent (0.5 ml), 1a and 2A at 100 ℃ The target product 3AA (Table 1, entry 1) was obtained in 83% yield in 24 hours (source: ACS catalyst.) under the optimal reaction conditions, the author first investigated the substrate range (Figure 3) of diaryl iodotrifluoromethylsulfonate through the reaction with 2 - (tert butyl Dimethylsilyl) pyridine 1a The aromatic products (3AB - 3ar) can be obtained with good to excellent yields from the substituents with neutral, electron deficient and electron rich substituents in the interposition and Antiposition of benzene rings More importantly, the reaction conditions can be compatible with a variety of functional groups The substrate containing two substituents on the aryl group can also obtain the corresponding product (3As - 3Au), and the yield is high In addition, the naphthalene ring can also be coupled and the product 3av can be obtained in medium yield It is worth noting that the disubstituted product 3aw can be successfully obtained by increasing the amount of diaryl iodine trifluoromethylsulfonate (source: ACS catalyst.) then, the author took diaryl iodotrifluoromethylsulfonate 2b as the aryl source, and investigated the application scope of alkylmethyl substrate 1a When there are substituents of different sizes on silicon atom, i.e dimethyl, diethyl, di-n-butyl, diisopropyl and dibenzyl, the reaction only takes place on silicon methyl, and the aromatization product 3bb-3hb is obtained in high yield In addition, 2-methylsilylmethylpyridine derivatives with different substituents on the silicon atom can also successfully obtain the corresponding product 3ib-3ob Similarly, with the increase of the amount of diaryl iodotrifluoromethylsulfonate, the two methyl groups on the 2-dimethylpyridinoline silane will be aromatized at the same time, and 3PB will be obtained in medium yield It is gratifying that pyrimidine is also an effective guiding group (3qb) for this reaction (source: ACS catalyst.) after the successful aromatization of silyl methyl, the author hopes to extend the method to other electrophilic reagents After optimizing the reaction conditions, the author found that both sulfonylazide 4 and dioxazolone 6 are suitable amide sources, and a series of C (SP 3) - H amidation products (5a - 5D, 7a - 7D) can be obtained in good yields (source: ACS catalyst.) finally, based on mechanism experiments and previous literature reports, the author proposed the IR III / IR V catalytic cycle mechanism (Figure 9) Firstly, [(Cp * IRCL 2) 2] and agntf 2 were exchanged to form ircp * (NTF 2) 2, which coordinated with pyridyl silane derivative 1 to form key IR complex a Subsequently, diaryldionium salt 2 and intermediate a are oxidized to form IR V substance B Then B is reduced and eliminated to obtain the required product 3 and regenerate the catalyst (source: ACS catalyst.) Summary: Zhao Dongbing's team developed the first case of intermolecular C (SP 3) - H-bond arylation / amidation of silicomethyl by using the guiding group strategy, which is the most direct and effective method to synthesize benzyl silane and amino substituted silane These products are widely used as chemical raw materials for the preparation of drugs and other bioactive compounds In addition, pyridine guiding group on silicon atom is favorable for further transformation, and can be easily removed by simple nucleophilic attack.