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The synthesis of silicon ring has an important application in the fields of organic synthesis, pharmaceutical chemistry and material chemistry. Due to the lack of general synthesis methods, the research on Synthesis of silicon containing tetrahydronaphthalene and benzocycloheptanosilane is relatively less. Recently, Zhao Dongbing group of Nankai University published a paper in angelw. Based on the cross coupling reaction of PD catalyzed silicon, an efficient and universal ring expanding method has been realized, which can prepare a variety of silicon containing tetrahydronaphthalene and benzocycloheptanosilane derivatives. Article link doi: 10.1002/anie.202001539
During the period of skip reading → epidemic situation, the annual package of chemical plus network enterprises will buy for one year and give one year as a gift (picture source: angel. Chem. Int. ed.) "carbon / silicon conversion" is an innovative strategy in the development of new materials, drugs and pesticides, while the silicon containing tetrahydronaphthalene and benzocycloheptane structural units are common in many commercial drugs and natural species (Figure 1a). In view of this, it is of great significance to study the synthesis of tetrahydronaphthalene and benzocycloheptanosilane containing silicon. However, up to now, due to the lack of general synthesis methods, the development of tetrahydronaphthalene and benzocycloheptane containing silicon has been seriously insufficient (Figure 1a). However, there are some disadvantages in the typical synthesis methods, such as low generality, poor reaction conditions and multi-step reaction. Therefore, it is urgent to develop a general and efficient strategy to synthesize this kind of skeleton. (image source: angelw. Chem. Int. ed.) in the past few decades, palladium catalyzed hyama Denmark cross coupling reaction has become an efficient strategy for the construction of new carbon carbon bonds (Figure 1b). In general, the - Sir3 group acts as the leaving group in the cross coupling reaction and is converted into the corresponding silicon by-product. It is suggested that Hiyama Denmark cross coupling reaction can be used in intramolecular ring expansion reaction to rapidly construct various silicon ring frameworks. The experimental results show that due to the inherent ring tension of penta silicates and the properties of releasing Lewis acid, the tendency of tetra and penta silicates to be activated into penta coordinated silicates by nucleophiles is enhanced (Figure 1c). Therefore, based on the coupling reaction of organosilicon, the four and five membered silicon rings seem to be more prone to transition metallization, so that the activity of the reaction can be further enhanced by the introduction of aryl bromide in the ortho position, the intramolecular Hiyama Denmark cross coupling can be realized, and the ring expansion products can be obtained. In addition, due to the cross coupling of aryl halides and O or N-nucleophiles in the reaction process, it is necessary to select appropriate nucleophiles and catalytic systems to inhibit the process, so as to realize ring expansion. In this paper, the author mainly introduces the silicon based cross coupling reaction under PD catalysis to realize the ring expansion of four and five element silicon rings (Figure 1D). (picture source: angelw. Chem. Int. ed.) cyclobutanosilane (SCB) has been widely used as the synthon of silicon in transition metal catalytic reaction due to its high tension and Lewis acid. Therefore, the author used the cyclobutanosilane derivative 1A as the model substrate to screen the PD catalytic conditions. Through a large number of screening conditions, when 5 mol% of PD (ptbu3) 2, tmsnet2 (1.5 equivalent) and tbuoh are used as solvent and nucleophile reagent, the target product 2a with 87% yield can be obtained by reacting for 24 hours at 80 ℃. Then, the scope of the substrate cyclobutanosilane 1 and nucleophiles was studied (Figure 2). When the 3-6 position of the benzene ring has an electrically neutral, electron rich or electron absorbing group, a good yield of 2b-2i can be obtained under the above standard conditions. The substrates containing 3,6 -, 4,5 -, 5,6 -, 4,6 - and 5,6-disubstituted were also able to react successfully, and the corresponding product 2j-2q was obtained. At the same time, the corresponding heterocyclic product 2R can also be obtained when there are heterocyclic groups in the neighborhood. In addition, the nucleophiles were also studied. When tbuoh is changed to different alcohols and phenols as nucleophiles and solvents, the corresponding product 2s-2w can be obtained. At the same time, bromine and heterocyclobutanosilane groups were introduced into the 1 and 8 positions of naphthalene, respectively, and the reaction was still smooth, so that the product 2x-2y was obtained. (image source: angelw. Chem. Int. ed.)
In order to obtain seven membered cyclobenzocycloheptane silane products, the author changed cyclobutanosilane 1a to cyclopentasilane 3a. Under the above standard conditions, only trace amount of target product 4A was obtained. Therefore, the reaction conditions were extensively selected. When the mixed solvent of DMF / cyoh (1:1) was used (cyoh as nucleophilic reagent), the product 4A with 91% yield could be obtained by reacting for 24 hours at 150 ℃. Subsequently, the author expanded the substrate range of cyclopentasilane 3 (Figure 3). The substituents of benzene ring are not affected by electronic effect, and the required product 4b-41 can be obtained. At the same time, the results of multi substituent substrate are also good, and the multi substituent product 4m-4q is obtained. In addition, both cyclohexyl methanol and phenol can be used as effective nucleophiles to obtain the product 4r-4s. When the bromine and cyclopentasilane groups are introduced into the 1 and 8 positions of naphthalene, 4 T of octaary silicon ring product can be obtained. (image source: angelw. Chem. Int. ed.) in order to further prove the practicability of the method, the author modified the product 4H (Figure 4). For example, reaction in 40% HF THF / H2O solution for 1 hour at room temperature resulted in the cleavage of - ocy group and the product 5A with 98% yield. At the same time, the product 5B (79%) was easily obtained by alkyl substitution of - ocy group with organic lithium reagent in 4 hours. If tbuooh / SeO2 is used, hydrolysis can be carried out in DCM to obtain silanol 5C with 85% yield. In addition, cyclic hydrosilanes can be obtained by reducing Si-O bond in the product for 4H with LiAlH4 for 5D (the yield is 71%, which can be used as the synthesis intermediate of hydrosilylation reaction). In addition to reduction, 2-hydroxy-arylbutanol 5E (intermediate of bioactive molecules) can also be obtained by oxidation of Tamao for 4H in 80% yield. When NIS / AGF was used to react with 4 hours, ring opening and diiodination were realized. 1-iodine-2 - (4-iodobutyl) benzene 5F was obtained in 56% yield. (picture source: angelw. Chem. Int. ed.) in addition, the author further functionalized the carbon ring in the product, so as to obtain a variety of tetrahydronaphthalene containing silicon or benzocycloheptanosilane derivatives (Figure 4). First, bromination was carried out at the 5-position of product 5b, and the product 6 was obtained in 70% yield. The product 6 can be further modified. For example, in DMSO, compound 6 can be oxidized smoothly to obtain brominated silane benzocycloheptanol 7 in 58% yield. In the presence of DBU, bromine in 6 can be easily eliminated to form unsaturated benzocycloheptane 8. 8 can also be used as a good reaction intermediate for a variety of transformations, such as further oxidation by PCC or DDQ to obtain the corresponding silane ketone 9 or conjugate system product 10. (photo source: angelw. Chem. Int. ed.) in order to further understand the reaction mechanism, the author conducted some control experiments. First of all, the author used cyclohexylsilane 11 as the substrate, under the above two standard conditions (eq.1-2), no ring expansion occurred, which shows that the high ring tension of silicon ring is essential in the cross coupling reaction of PD catalyzed silicon in the molecule. If pd0 catalyst (eq.3) is not used, the reaction of cyclobutanosilane 1x does not take place under the standard conditions, indicating that 1x does not form a free five coordinated silicon intermediate in tbuoh. At the same time, in the presence of PD (ptbu3) 2 (Eq. 4), if substrate 13 is reacted under standard conditions, only 100% of the raw materials are obtained, indicating that cyclobutanosilane is not active before undergoing intramolecular transition metallization. In addition, the competitive experiment between cyclobutanosilane 13 and aryl bromide 14 also shows that the oxidation addition of C-Br bond is much faster than the insertion of c-Si bond, and the reaction starts from the oxidation addition of C-Br bond, because in the presence of the stoichiometric PD (ptbu3) 2, the dimerization of 14 successfully generates compound 15 (eq.5). (picture source: angelw. Chem. Int. ed.) based on the above experiments and the literature review, the author proposed a possible reaction mechanism (Figure 5). Firstly, pd0 was oxidized to C-Br bond of 1 or 3 to form pdii intermediate a, and then through intramolecular transfer metallization, intermediate B (path a) was obtained. Then, in the presence of Roh and alkali, intermolecular etherification was carried out to obtain intermediate C of Si or bond. Finally, target product 2 or 4 was obtained by reduction elimination, and pd0 catalyst was regenerated. It is worth noting that in the presence of alkali and hor, pdii intermediate a can also obtain ar pdii or species B 'through another br / or exchange pathway, and then intermediate C (path B) can be obtained through σ - bond decomposition between pdii or bond and C (SP3) - Si bond. (image source: angelw. Chem. Int Ed.) Summary: Zhao Dongbing research group of Nankai University reported the cross coupling reaction based on PD catalyzed silicon, and realized an efficient and universal ring expanding method. It can synthesize a variety of six eight membered silicon ring derivatives through ring expanding of cyclobutylene (pentyl) silane substrate. The reaction has good functional group tolerance, and is also the synthesis of a variety of silicon containing tetrahydronaphthalene and benzocycloheptane derivatives One of the most effective and general methods. Writer: Shanshan
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