JACS: photocatalytic dehydrogenation and coupling of C-H bond of benzyl group and aldehyde group

If two different C-H bonds can be selectively cleaved and dihydrogen can be removed to form a new C-C bond, it will provide a convenient method for the preparation of organic ketones However, due to the inertness of C-H bond, the complex decomposition process of σ bond is difficult to be realized in dynamics In addition, this is usually not good for thermodynamic equilibrium based on bond dissociation energy So far, the reported examples of dehydrogenation C-H / C-H cross coupling are limited to: (1) the reaction of phenol with low oxidation potential and tetrahydroisoquinoline substrate; (2) the reaction of benzene derivatives substituted by heteroatom functional groups, which can induce metal to close to specific aromatic C-H bond Recently, Masahiro Murakami and Naoki Ishida of Kyoto University in Japan reported the C-H / C-H cross coupling reaction of dehydrogenation of alkylbenzene with aldehydes catalyzed by light, iridium and nickel to synthesize α - arylketone derivatives In addition, α - aminoketone can be formed by the cross coupling reaction of n-methylamide and aldehyde This strategy provides a convenient and direct way for the synthesis of α - substituted ketones Relevant research results were published in J am Chem SOC (DOI: 10.1021 / JACS 9b13920) (source: J am Chem SOC.) at present, researchers have realized the direct arylation, acylation, alkoxycarbonylation, alkenylation and carboxylation of C (SP 3) - H bond catalyzed by nickel catalyst and photocatalyst under light irradiation In order to expand the scope of application of C (SP 3) - H bond coupling reagent (scheme 1), the author selected toluene derivatives and aldehydes as model substrates, and finally determined the best conditions as follows: IR [DF (CF 3) PPy] 2 (dtbbpy) pf 6 and NIBR 2 (dtbbpy) as catalysts, 4-methoxytoluene (1) and octanal (2) in ethyl acetate solution with blue LED (40 W, λ α - arylacetone (3) can be obtained in 73% yield after 20 hours of irradiation with max = 463nm) Under the optimal reaction conditions, various substituted alkylaromatics and octanal can be dehydrogenated and coupled successfully, and the corresponding ketone (5 - 23) can be obtained in medium to good yield Methoxy (9), ester (14), cyano (15), halogen (16 - 18) and other functional groups have good tolerance (Table 1) (source: J am Chem SOC.) then the author investigated the universality of various aliphatic aldehydes (Table 2) The corresponding ketone (24 - 34) can be obtained by the reaction of aliphatic aldehyde with 1 The yield is 56% - 80% Linear aldehydes (24 - 26) and α - branched aldehydes (27 - 29) are suitable substrates (source: J am Chem SOC.) based on a series of mechanism experiments, the author speculated a possible reaction mechanism (scheme 4), which includes five steps (step 1-5) Step 1: iridium hexafluorophosphate (III) a and nickel bromide (II) B are ion exchanged to form iridium bromide (III) complex C Step 2: when C is excited by absorption light, an electron transfers from bromine ion to iridium (III), producing iridium (II) species E and bromine radicals Iridium (II) species e (E 1 / 2 [IR (III) / IR (II)] = − 1.37 V vs SCE) provides an electron to nickel (II) species B (E 1 / 2 [Ni (II) / Ni (0)] = − 1.2 V vs SCE) to generate nickel (I) species F and iridium bromide (III) Step 3: the bromine radicals generated in step 2 pull out the hydrogen atom in the C-H bond of the benzyl and aldehyde groups to obtain the species of benzyl and acyl radicals and HBr Step 4: acyl and benzyl radicals are successively added with nickel (I) species f to form nickel (III) complex h, which is then reduced to ketone 3 and nickel (I) species F Step 5: nickel (I) species f reacts with HBr to generate H2 and nickel (II) bromide species B, and re enters the catalytic cycle of step 1 (source: J am Chem SOC.) aromatics can stabilize benzyl radicals Similarly, nitrogen atoms can also stabilize the carbon clusters they bind to Whether the C-H bond of the adjacent nitrogen atom can participate in the dehydrogenation coupling reaction with the aldehyde C-H bond is investigated The results show that α - aminoketone 41 and 43 can be obtained by the reaction of N, N-Dimethylacetamide (40) and N, N-dimethylformamide (42) with octaldehyde (2) in 70% and 32% yield respectively under the standard conditions (source: J am Chem SOC.) conclusion: the photoinduced C-H / C-H cross coupling reaction of alkylbenzene and aldehyde has been developed This provides a simple and direct method for the synthesis of α - arylketones In addition, α - aminoketone can also be synthesized by the reaction of n-methylamide and aldehyde via similar C-C bond.