- Aromatization as an Impetus to Harness Ketones for Metallaphotoredox-Catalyzed Benzoylation/Benzylation of (Hetero)arenes
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Herein we report ketones as feedstock materials in radical cross-coupling reactions under Ni/photoredox dual catalysis. In this approach, simple condensation first converts ketones into prearomatic intermediates that then act as activated radical sources for cross-coupling with aryl halides. Our strategy enables the direct benzylation/benzoylation of (hetero)arenes under mild reaction conditions with high functional group tolerance.
- Lee, Shao-Chi,Li, Li-Yun,Tsai, Zong-Nan,Lee, Yi-Hsin,Tsao, Yong-Ting,Huang, Pin-Gong,Cheng, Cheng-Ku,Lin, Heng-Bo,Chen, Ting-Wei,Yang, Chung-Hsin,Chiu, Cheng-Chau,Liao, Hsuan-Hung
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- Transition-Metal-Free Oxidation of Benzylic C-H Bonds of Six-Membered N-Heteroaromatic Compounds
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A novel oxidation of benzylic C-H bonds for the synthesis of diverse six-membered N-heteroaromatic aldehydes and ketones has been developed. The obvious advantages of this approach are the simple operation, mild reaction conditions, and without use of toxic reagent and transition metal. The present method should provide a useful access for the synthesis and modification of N-heterocycles.
- Gao, Xianying,Han, Shuaijun,Zheng, Maolin,Liang, Apeng,Zou, Dapeng,Wu, Yusheng,Wu, Yangjie,Li, Jingya
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p. 4040 - 4049
(2019/04/30)
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- Arylation of Aldehydes to Directly Form Ketones via Tandem Nickel Catalysis
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A nickel-catalyzed arylation of both aliphatic and aromatic aldehydes proceeds with air-stable (hetero)arylboronic acids, with an exceptionally wide substrate scope. The neutral condition tolerates acidic hydrogen and sensitive polar groups and also preserves α-stereocenters of some chiral aldehydes. Interestingly, this nickel(0) catalysis does not follow common 1,2-insertion of arylmetal species to aldehydes and β-hydrogen elimination.
- Lei, Chuanhu,Zhu, Daoyong,Tangcueco, Vicente Iii Tiu,Zhou, Jianrong Steve
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supporting information
p. 5817 - 5822
(2019/08/26)
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- Copper-Catalyzed Aerobic Oxygenation of Benzylpyridine N-Oxides and Subsequent Post-Functionalization
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A copper-catalyzed aerobic oxidation of benzylpyridine N-oxides is reported. The N-oxide moiety acts as a built-in activator for the benzylic methylene oxidation, without requirement of additives. Reaction conditions were identified which suppress undesired benzoylpyridine formation via N-deoxygenation involving intermolecular oxygen transfer. The versatility of the N-oxide group of the benzoylpyridine N-oxide reaction products for post-functionalization of the pyridine ring is demonstrated through efficient C–C, C–N, C–O and C–Cl bond forming procedures, with both nucleophiles and electrophiles. Finally, the applicability of the new synthetic methodology is demonstrated in an alternative route towards the antihistaminic drug Acrivastine via three consecutive N-oxide activated C–H functionalization processes, starting from picoline N-oxide. (Figure presented.).
- Sterckx, Hans,Sambiagio, Carlo,Médran-Navarrete, Vincent,Maes, Bert U. W.
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supporting information
p. 3226 - 3236
(2017/09/13)
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- Oxidant-Controlled C-sp2/sp3-H Cross-Dehydrogenative Coupling of N-Heterocycles with Benzylamines
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Oxidant controlled ionic liquid mediated cross-dehydrogenative coupling (CDC) of benzylamines with N-heterocycles having sp2 or sp3 carbon resulted in the formation of C-benzoylated or alkenylated products. Benzoylation of N-heterocycles occurs via (NH4)2S2O8 catalyzed benzoyl radical formation. An oxidative alkenylation of N-heterocycles having C-sp3 carbon (2-methylaza-arenes) occurs via deamination of benzylamine followed by C-sp3-H bond activation in high stereoselectivity. Both benzoylation and alkenylation protocols are metal-free, green, simple, efficient, and tolerate a wide variety of functional groups.
- Sharma, Rohit,Abdullaha, Mohd,Bharate, Sandip B.
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p. 9786 - 9793
(2017/09/23)
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- Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen
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The methylene group of various substituted 2- and 4-benzylpyridines, benzyldiazines and benzyl(iso)quinolines was successfully oxidized to the corresponding benzylic ketones using a copper or iron catalyst and molecular oxygen as the stoichiometric oxidant. Application of the protocol in API synthesis is exemplified by the alternative synthesis of a precursor to the antimalarial drug Mefloquine. The oxidation method can also be used to prepare metabolites of APIs which is illustrated for the natural product papaverine. ICP-MS analysis of the purified reaction products revealed that the base metal impurity was well below the regulatory limit.
- Sterckx, Hans,De Houwer, Johan,Mensch, Carl,Herrebout, Wouter,Tehrani, Kourosch Abbaspour,Maes, Bert U.W.
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supporting information
p. 144 - 153
(2016/04/05)
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- DECARBOXYLATIVE CROSS-COUPLING AND APPLICATIONS THEREOF
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Methods described herein enable the production of numerous molecular species through decarboxylative cross-coupling via use of photoredox and transition metal catalysts. For example, methods described herein enable the production of numerous molecular species through decarboxylative cross-coupling via use of photoredox and transition metal catalysts. A method described herein, in some embodiments, comprises providing a reaction mixture including a photoredox catalyst, a transition metal catalyst, a coupling partner and a substrate having a carboxyl group. The reaction mixture is irradiated with a radiation source resulting in cross-coupling of the substrate and coupling partner via a mechanism including decarboxylation, wherein the coupling partner is selected from the group consisting of a substituted aromatic compound and a substituted aliphatic compound.
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Page/Page column 32; 40
(2015/12/09)
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- Merging Photoredox and Nickel Catalysis: The Direct Synthesis of Ketones by the Decarboxylative Arylation of α-Oxo Acids
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The direct decarboxylative arylation of α-oxo acids has been achieved by synergistic visible-light-mediated photoredox and nickel catalysis. This method offers rapid entry to aryl and alkyl ketone architectures from simple α-oxo acid precursors via an acyl radical intermediate. Significant substrate scope is observed with respect to both the oxo acid and arene coupling partners. This mild decarboxylative arylation can also be utilized to efficiently access medicinal agents, as demonstrated by the rapid synthesis of fenofibrate. The direct decarboxylative arylation of α-oxo acids has been achieved by synergistic visible-light-mediated photoredox and nickel catalysis. This method offers rapid entry to aryl and alkyl ketone architectures from simple α-oxo acid precursors via an acyl radical intermediate. Significant substrate scope is observed with respect to both the oxo acid and arene coupling partners.
- Chu, Lingling,Lipshultz, Jeffrey M.,Macmillan, David W. C.
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supporting information
p. 7929 - 7933
(2015/06/30)
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- One-pot synthesis of heteroaryl and diheteroaryl ketones through palladium-catalyzed 1,2-addition and oxidation
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A synthetic method was developed for the preparation of heteroaryl and diheteroaryl ketones from aldehydes and organoboronic acids through a palladium-catalyzed 1,2-addition and oxidation that uses an aryl iodide as the oxidant. This one-pot process shows high tolerance for a broad range of heterocyclic substrates by using 1.0-3.0 mol-% of the catalyst that is formed from allylpalladium chloride dimer and a thioether-imidazolinium chloride. In addition to fine-tuning the catalytic system, the use of a sterically hindered aryl iodide that has a substituent at the ortho position, such as 2-iodotoluene, is important to obtain the desired ketones with heterocyclic moieties in good to excellent yields. The one-pot synthesis of heteroaryl and diheteroaryl ketones was achieved by a palladium-catalyzed 1,2-addition and oxidation. This catalytic process with 1.0-3.0 mol-% catalyst loading tolerates a broad range of heterocyclic substrates to give ketones with heterocyclic moieties in good to excellent yields. Copyright
- Kuriyama, Masami,Hamaguchi, Norihisa,Sakata, Keisuke,Onomura, Osamu
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p. 3378 - 3385
(2013/06/27)
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- DMC mediated one pot synthesis of biaryl ketones from aryl carboxylic and boronic acids
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Synthesis of biaryl ketones has been realized from aryl carboxylic acids in the presence of DMC, facilitated by palladium catalyst under thermal condition. This methodology gives the introduction of carbonyl functionality in one pot from corresponding ary
- Pathak, Arunendra,Rajput, Chatrasal S.,Bora, Pushkar S.,Sharma, Somesh
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p. 2149 - 2150
(2013/05/08)
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- Polar effects in free-radical reactions. A novel homolytic acylation of heteroaromatic bases by aerobic oxidation of aldehydes, catalysed by N-hydroxyphthalimide and Co salts
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A new process for the homolytic acylation of protonated heteroaromatic bases is described; an N-oxyl radical (PINO) generated from N-hydroxyphthalimide by air oxygen and Co(II) abstracts a hydrogen atom from an aldehyde. The resulting nucleophilic acyl radical adds to a heteroaromatic base, which is then rearomatised in a chain process. Quinazoline has an anomalous behaviour, giving 3H-quinazolin-4-one as the only reaction product.
- Minisci, Francesco,Recupero, Francesco,Cecchetto, Andrea,Punta, Carlo,Gambarotti, Cristian,Fontana, Francesca,Pedulli, Gian Franco
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p. 325 - 328
(2007/10/03)
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- Homolytic Acylation of Protonated Pyridines and Pyrazines with α-Keto Acids: The Problem of Monoacylation
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The silver-catalyzed decarboxylation of α-keto acids by persulfate leads to acyl radicals, which can effect the selective homolytic acylation of pyridine and pyrazine derivatives.Compared with the previously developed source of acyl radicals by hydrogen abstraction from aldehydes, this procedure is more effective in monoacylation when multiple positions of high nucleophilic reactivity are available in the heterocyclic ring.Although the introduction of an acyl group strongly activates the heterocyclic ring toward further substitution, monoacylation can be achieved by taking advantage of the difference in basicity and lipophilicity between the starting base and the monoacylation products in a two-phase system.
- Fontana, Francesca,Minisci, Francesco,Barbosa, Maria Claudia Nogueira,Vismara, Elena
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p. 2866 - 2869
(2007/10/02)
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- REACTION OF METHOXY-N-HETEROAROMATICS WITH PHENYLACETONITRILE UNDER BASIC CONDITIONS
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The monomethoxyl derivatives of various ?-electron deficient N-heteroaromatics reacted with phenylacetonitrile in tetrahydrofuran in the presence of sodium hydride to give α-phenyl-N-heteroareneacetonitriles in the yields ranging from 45 to 78percent.On the contrary, the reaction of these methoxyl derivatives with ethyl cyanoacetate or malononitrile under similar conditions was restricted within narrow limits.The synthesis of benzoyl-N-heteroaromatics by the air-oxidation of α-phenyl-N-hetroareneacetonitriles was described additionally.
- Yamanaka, Hiroshi,Ohba, Setsuya
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p. 895 - 909
(2007/10/02)
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- CONVERSION OF INDOLES INTO QUINOLINES THROUGH THE N-1-C-2 FISSION BY SINGLET-OXYGEN AS A MODEL EXPERIMENT OF BIOMIMETIC SYNTHESIS OF QUININE ALKALOIDS
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Photo-oxygenation of indole-3-acetaldehydes (28-30) followed by treatments with dimethyl sulphide and then dilute acetic acid gave 4-acylquinolines (13, 31 and 32), respectively.
- Ihara, Masataka,Noguchi, Kazuharu,Fukumoto, Keiichiro,Kametani, Tetsuji
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p. 2109 - 2114
(2007/10/02)
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- Studies on Organometallic Compounds. III. Reaction of Trimethylstannylazines with Acyl Chlorides. A Novel C-C Bond Formation of Pyridine Nuclei
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Introduction of an acyl group at the α-, β-, and γ-positions of pyridine nuclei was accomplished. 2-Trimethylstannyl-pyridine and -quinoline and 1-trimethylstannylisoquinoline directly reacted with various acyl chlorides to give the corresponding 2-pyridyl, 2-quinolyl, and 1-isoquinolyl ketones, respectively.Reaction of 3-trimethylstannylpyridine, -quinoline, and -isoquinoline with acyl chlorides proceeded smoothly under catalysis by PdCl2 or PdCl2(PPh3)2 to afford the corresponding ketones in good yields.Similary, 4-pyridyl, -quinolyl, and -isoquinolyl ketones were prepared from corresponding 4-trimethylstannyl derivatives and acyl chlorides.Keywords--trimethylstannylazine; palladium-catalyzed reaction; acylation; palladium dichloride; dichlorobis(triphenylphosphine)palladium(II)
- Yamamoto, Yutaka,Yanagi, Akihiko
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p. 2003 - 2010
(2007/10/02)
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- A SIMPLE METHOD FOR INTRODUCTION OF ACYL GROUPS INTO PYRIDINE NUCLEI VIA TRIMETHYLSTANNYL-PYRIDINES AND QUINOLINES.
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The 2-trimethylstannyl (TMSn) derivatives of pyridine and quinoline were directly treated with acyl chlorides to afford the corresponding 2-acyl-pyridines and -quinolines in good yields.On the other hand, replacement of the 3- and 4-TMSn groups by acyl groups was satisfactorily achieved by catalysis of palladium compound such as PdCl2 or PdCl2(PPh3)2.
- Yamamoto, Yutaka,Yanagi, Akihiko
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