Chem. SCI, Naoto Chatani research group: rhodium (II) catalyzed branched chain selective C-H alkylation of arylsulfonamide

In organic chemistry, transition metal catalyzed C-H bond activation is a direct and site selective method At present, researchers have developed a series of responses through directed base strategy In particular, C-H bond alkylation using olefins as substrates provides an atom economy strategy to obtain target products In 1993, Murai reported the alkylation of aromatic ketones and alkenes by ortho-c-h bond catalyzed by carbonyl oriented ruthenium Subsequently, a large number of regioselective C-H alkylation reactions using guiding groups have been reported However, most of the reports are mainly linear selective alkylation, and only a few are branched chain selective alkylation (Figure 1a) In this respect, the researchers used the strategy of non oriented group for alkylation of 1,3,4-oxadiazole, indole, benzimidazole, benzoxazole, benzothiazole, pyridine and acridine (A-J) In addition, some directed group strategies have been used in the selective alkylation of branched chains (I-X) However, the above branched alkylation usually uses activated olefins as the substrate, and seldom uses non activated end olefins as the substrate (Figure 1b) Recently, the research group of Naoto chanati, Professor of Osaka University, Japan reported that RH (II) catalyzes the branched chain selective C-H bond alkylation of arylsulfonamide and vinyl silane, using 8-aminoquinoline as the guiding group The results were recently published in Chem SCI (DOI: 10.1039 / c9sc04308j) (photo source: chem SCI.) firstly, the author investigated the influence of the guiding group on the selectivity of the branched chain, and finally determined 8-aminoquinoline as the guiding group, and the branched chain / linear ratio reached 92:8 (table 1) Then, using 1A as the model substrate, the effects of catalyst and additives were investigated Finally, the optimal reaction conditions were determined as follows: [Rh (OAC) 2] 2 as the catalyst, 3-chloro-2-methylbenzoic acid as the additive, toluene as the solvent, the substrate reacted at 160 ℃ for 24 hours, and the branched products were obtained with 72% yield and 86:14 selectivity (Table 2) (picture source: chem SCI.) (picture source: chem SCI.), the author then inspected the range of substrate (scheme 2) Firstly, the effect of functional groups was investigated The reaction is compatible with ether, alkyl, fluorine, chlorine, amide, trifluoromethyl, benzyl bromide and other substituents, and has good branch chain selectivity It should be noted that the formation of Dialkylation products was not observed in this reaction At the same time, the author also investigated different types of vinyl silanes, which can give the corresponding branched alkylation products (2ab-2ae and 2PA PC, table 3) (photo source: chem SCI.) next, the author conducted a series of mechanism verification experiments Using sulfonamide 1C as the substrate, the H / D exchange of the reaction took place obviously under the condition of CD 3cood, which proved that the activation process of C-H bond was reversible (Figure 2a) In the reaction of deuterium sulfonamide 1c-d 5 with triethylvinyl silane, the author observed that there was 0.34 deuterium in β position, but no deuterium in α position, which indicated that the reaction might involve the mechanism of hydrogen metallization (Figure 2b) When cd3cood was used as the only deuterium reagent, only 0.51 deuterium occurred at the β position in the product 8 given by 1c and triethylsilane, indicating that the reaction also included the process of carbon metallization (Figure 2C) (picture source: chem SCI.) in KIE experiment, the ratio of KH / KD is 1.06, which shows that C-H bond activation is not a decisive step (Figure 3a) In addition, the stoichiometric reaction of 1C with [Rh (OAC) 2] 2 was carried out to obtain Rh complex 10 and the absolute configuration of single crystal (Figure 3B) After that, the target product of branched chain (Figure 3C) can be successfully obtained by catalytic reaction of compound 10, which shows that the compound participates in catalytic cycle (picture source: chem SCI.) based on the above deuterium experimental results, the author gives two main catalytic models First of all, Rh and sulfonamide form intermediate a, which releases two molecules of carboxylic acid to form B, which is oxidized and added to the ortho-c-h bond to form rh-h complex C Then, vinyl silane was inserted into rh-h bond to form intermediate D, which was reduced to Rh complex E Finally, e releases the product under acid condition and regenerates Rh (II) catalyst Another catalytic cycle is that after the formation of intermediate C, two carboxylic acids dissociate and coordinate to RH to form metal ring intermediate F The olefin of vinyl silane is transferred into the rh-c bond of F to form intermediate g, which reacts with bimolecular acid to form product (Figure 4) (photo source: chem SCI.) Summary: naotochatani research group reported for the first time rhodium catalyzed alkylation of arylsulfonamides by branch chain selective C-H bond This method uses non activated vinyl silane as substrate and 8-aminoquinoline as guide group The research team carried out detailed mechanism verification experiments in the research, and proposed two possible catalytic processes of hydrogen metallization and carbon metallization.