Angelw: Ru (II) catalyzes the series reaction of C-H Allylation and [3 + 2] dipolar cycloaddition of allylic acetals

Azomethionine imines have been widely used in cycloaddition reactions with various coupling agents such as alkenes, alkynes and allylites In addition, in the C-H functionalization reaction, researchers have carried out in-depth research on the formation of heterocyclic compounds from olefins, including nucleophilic addition of guide groups and olefins or electrophilic addition of guide groups and M-C intermediates Recently, in Su Kim group of chengjunguan University in South Korea has developed Rh (III) catalytic C-H functionalization and in-situ cyclization of Morita Baylis Hillman adduct to obtain 2-benzoazazol, bridgebiphenylbenzoxazol and 2-naphthol derivatives It was found that the ester group on the MBH adduct can reduce the energy barrier of the migration insertion step and enhance the catalytic cycle Recently, the research team of professor in Su Kim has made new progress They found that allylic acetals can be inserted into ruthenium ring species through olefins to obtain vinyl ether adducts They further experienced [3 + 2] dipolar cycloaddition to generate valuable indenpyrazolpyrazolone (scheme 1b) This is also the first case in which allylic acetals are used as the highly electrophilic acrolein onium precursor in C-H allylation The related research results were published in angelw Chem Int ed (DOI: 10.1002 / anie 201903983) (source: angelw Chem Int ed.) at the beginning of the study, the author used azomethionine imine 1a and 3,3-dimethoxy-1-propene 2A as model substrates to screen the reaction conditions (Table 1) It is gratifying that at 40 ℃, the catalytic combination of [Ru (p-cymene) Cl 2] 2 and agsbf 6 can promote the coupling reaction, and the indenpyrazolpyrazolone derivative 3A can be obtained in 20% yield The control experiments show that the cation ruthenium catalyst plays an important role in the reaction (entry 2) Then through the investigation of the conditions of additives and solvents, the author found that the cyclized product 3A (entry 12) can be obtained with 93% yield in 12 hours reaction at 40 ℃ with cationic Ru (II) as catalyst, agsbf 6 and lithium acetate as additives, HFIP as solvent (source: angelw Chem Int ed.) after determining the optimal reaction conditions, the author first investigated the application range of hetero (aryl) azomethionine imine (Table 2) A series of O -, M - and p-substituted imines were successfully coupled with 2a, and the indenpyrazolpyrazolone derivative 3A - 3R was obtained with a yield of 50-98% Bisubstituted or trisubstituted electron rich azomethionine imines 1s and 1t can also be functionalized by C-H In addition, 1-naphthyl or heterocyclic azomethionine imine was also suitable for the reaction, and 3U, 3V and 3x were obtained in medium yield The substrate 1y and 1z derived from 5-cyclohexyl and unsubstituted pyrazoline-3-one can also react smoothly, and 3Y and 3Z (41%, Dr = 3:1) are obtained It should be noted that the non enantioselectivity of the transformation may be the effect of substituents on the pyrazoline-3-one ring (source: angelw Chem Int ed.) next, the author continued to investigate the substrate range of various allylic acetals 2b-2g (Table 3) The products 4B and 4C were obtained in 62% and 93% yields respectively The cyclized products 4D and 4E can be obtained by coupling the cyclic acetals 2D and 2E WITH 1a The symmetrical allyl acetal 2F can also react smoothly, and the corresponding indenpyrazolpyrazolone 4f can be obtained in 38% yield (source: angelw Chem Int ed.) in order to further illustrate the practicability of this method, the author uses this method to carry out late functionalization (scheme 2) of bioactive molecules with azomethionine imine guiding group The estrone derivative 5A can be transformed into 6A in medium yield In addition, substrate 5B derived from celecoxib (COX-2 selective non steroidal anti-inflammatory drugs) can react with 2a to selectively form target product 6B (source: angelw Chem Int ed.) finally, based on the mechanism experiment and DFT research, the author proposed a reasonable catalytic cycle (scheme 5) Initially, the cation Ru (II) catalyst coordinated with the nitrogen atom of azomethionine imine 1a to form ruthenium ring I Subsequently, the intermediate II of ruthenium ring was obtained by coordination and migration insertion of the product with allylmethoxycarbonyl 2A 'in situ Intermediate III is eliminated by β - o-to produce alkenyl intermediate IV Finally, the intermediate IV was cyclically added by internal type [3 + 2] dipoles to form ninhydazole pyrazolone product 3a, and the active Ru (II) catalyst was regenerated (source: angelw Chem Int ed.) Summary: the author has developed a method of Ru (II) catalyzed C-H functionalization of (hetero) arylazomethionine imine and allylic Acetal in series [3 + 2] dipolar cycloaddition This method has a wide range of substrates, high site selectivity and wide functional group tolerance, which provides a simple way for the construction of indenpyrazolpyrazolone with good yield.