JACS: Dong guangbin's group has realized ruthenium catalyzed reduction and cleavage of non tension C (aryl) - C (aryl) bond

The oxidation addition of transition metal (TM) and C-C bond is an important means to activate C-C bond A relatively inert C-C bond can be converted into two more reactive c-tm bonds, so as to carry out the dual functionalization of two carbon (scheme 1a) At present, researchers have developed a variety of catalytic methods for C-C bond cleavage / functionalization However, the range of C-C bonds that can be added to TM by oxidation is still limited (scheme 1b) (image source: J am Chem SOC.) in contrast, TM insertion into nonpolar and nonpolar C-C bonds is extremely rare In 1993, Milstein group reported the phosphine oriented C (aryl) - C (allyl) bond activation method (scheme 2a) by forming two five membered ring fused RH rings Recently, kakiuchi group has developed a RH catalyzed cleavage method of C (aryl) - C (allyl) bond by β - C elimination mechanism Recently, Dong guangbin's research group at the University of Chicago has been devoted to the study of the activation of the inactive C (aryl) - C (aryl) bond Through the Rh catalyst and the phosphite guiding group (DGS), the C (aryl) - C (aryl) bond of 2,2 '- bisphenol and the hydrogen catalytic cracking (scheme 2b) are realized However, the conversion still needs the ortho substituents in the 2,2' - bisphenol substrate Recently, Dong guangbin's research group developed a ruthenium catalyzed reduction cracking method of C (aryl) - C (aryl) bond, and studied its mechanism (scheme 2C), which was published in J am Chem SOC (DOI: 10.1021 / JACS 9b11605) (photo source: J am Chem SOC.) firstly, the author selected 2,2 '- (3-methylpyridyl) substituted biphenyls (1a) as the initial substrate to investigate a variety of RH catalysts ([Rh (C2H4) Cl] 2, [Rh (COD) Cl] 2, Rh (COD) 2ntf 2), but did not get the expected products (Table 1) However, the author added Nai to the reaction catalyzed by [Rh (COD) Cl] 2 to obtain 39% of C-C cracking products, but the exact role of Nai is not clear Although Ni (0), CO (0) and IR (I) complexes did not get the expected cracking products, RuCl 2 complexes showed significant reactivity Therefore, various ruthenium complexes (RuCl 3 · XH 2O, Ru3 (CO) 12, Cp * Ru (COD) Cl and Ru (COD) Cl 2) were investigated, and it was found that Ru (COD) Cl 2 had the best effect In addition to 1,4-dioxane, other solvents (such as toluene and THF) are also suitable for this conversion (photo source: J Am Chem Soc.) in addition to hydrogen, the author also screened other alternative reducing agents (Table 2) Under Ru catalysis, a variety of mild reducers (such as potassium formate and Hantzsch ester) are reactive and can produce the desired products Various secondary alcohols can also be used as hydrogen sources, among which Cyclopentanol is the best In addition, the mixture of silane and water (1:1) is also an excellent reductant (photo source: J am Chem SOC.) next, the author examined the substrate range of the reaction (Table 3) First of all, in addition to 3-methylpyridine, simple pyridine can also be used as an effective guiding group The 3,4 or 5 positions of aromatics can be substituted, but the steric hindrance may lead to a low yield of 3,3 '- disubstituted substrate The substituent of phenyl and furan showed good reactivity In addition, the reaction can also tolerate a series of functional groups, such as fluorine, chlorine, bromine, trifluoromethyl, Trifluoromethoxy 3, ester, amide, methoxy and methylsilyl ether When the fluorine atom is adjacent to DG, part of the C-F bond activation / cleavage products are formed, but the substitution of other positions by fluorine has no effect When ketone carbonyl exists in the substrate, the carbonyl is partially reduced to the corresponding alcohol, especially under the condition of transfer hydrogenation Due to the steric hindrance around the C (aryl) - C (aryl) bond, the larger binaphthylene derived substrate has no reactivity The results showed that pyridine with various electrical substitutions showed similar reactivity Other heteroaromatics, including pyrimidine, pyrazoles and quinolines, can also be used as effective guiding groups, while unstable oxazolines, Oxazoles and nitriles do not work (photo source: J am Chem SOC.) later, the author further studied the catalyst loading and reaction temperature under hydrogenation conditions (Table 4) When Ru loading decreased from 10 mol% to 2.5 mol%, the yield decreased slightly, and when Ru loading decreased to 1 mol%, the yield was still 55% At a lower temperature (110 ℃), the yield of the reaction is higher (90%), and the reaction temperature is further reduced to 70 ℃, showing moderate reactivity When the hydrogen pressure is reduced to 70 psi, the reaction efficiency will not be affected; when the hydrogen pressure is further reduced to 30 psi, the yield is low (65%) (photo source: J am Chem SOC.) in addition, the "one pot" method for C-C activation / C-C generation (EQ 1) was established After the hydrogenolysis of C (aryl) - C (aryl) bond, ruthenium catalyst remained active, and then the C-C cracking product was alkylated by adding acrylate This shows that C (aryl) - C (aryl) bond activation can be combined with subsequent functionalization by using a single catalyst (photo source: J am Chem SOC.) through calculation and experiment, the author explored the mechanism of ruthenium catalyzed C (aryl) - C (aryl) bond activation and proposed three possible reaction pathways (Figure 1): path a involves inserting Ru (II) dichloride ("rucl2") into C (aryl) - C (aryl) bond to obtain Ru (IV) The intermediate is then hydrogenolysed to obtain the monomer product Path B is initiated by the Ru (II) - hydrogen chloride species ("ruhcl"), which is produced by the single hydrogenation of the rucl2 precursor After the oxidation and addition of "ruhcl" and C (aryl) - C (aryl) bonds, the monomer product was obtained by C-H reduction and elimination, and then another monomer product was obtained by the reaction of the generated ruhcl aryl intermediate and H2, and the "ruhcl" catalyst was regenerated Path C is based on Ru (II) dihydrides ("RUH 2") generated by two hydrogenation of "RuCl 2" precursor In the same way, after inserting the intermediate RUH 2 into the C (aryl) - C (aryl) bond, two monomer products were obtained by bic-h reduction Finally, the generated Ru (0) reacts with H 2 to regenerate "RUH 2" species (photo source: J am Chem SOC.) conclusion: Dong guangbin's research group developed a ruthenium catalyzed activation method of non tension C (aryl) - C (aryl) bond, and investigated the limitations of the reaction and the range of substrates in detail In addition to hydrogen, other reagents such as Hantzsch ester, silane / alcohol can also be used as end reducers for reductive cracking; various heterocycles such as pyridine, quinoline, pyrimidine and pyrazole can be used as guiding groups In addition, the reaction mechanism was studied by DFT calculation and experiment, which improved the understanding of strong, non-polar and non tension chemical bond activation.