Expanding the Scope of C−H Amination through Catalyst Design

Espino, Christine G.; Fiori, Kristin Williams; Kim, Mihyong; Bois, J. Du

doi:10.1021/ja0446294

Cited by 622 publications

(408 citation statements)

References 17 publications

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“…Du Bois and colleagues have developed a bridged achiral rhodium catalyst Rh 2 (esp) 2 that has performed well at low catalyst loadings in both intra-and intermolecular C2H amination reactions (Fig. 12) [83][84][85] . Enantioselective intermolecular reactions of metal nitrenes are less developed than the parallel reactions of metal carbenes, although some significant examples have been reported 81,82,86,87 .…”

Section: C-h Functionalization By Metal Nitrenoidsmentioning

confidence: 99%

Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion

Davies

Manning

2008

Nature

2,174

812

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Novel reactions that can selectively functionalize carbon-hydrogen bonds are of intense interest to the chemical community because they offer new strategic approaches for synthesis. A very promising 'carbon-hydrogen functionalization' method involves the insertion of metal carbenes and nitrenes into C-H bonds. This area has experienced considerable growth in the past decade, particularly in the area of enantioselective intermolecular reactions. Here we discuss several facets of these kinds of C-H functionalization reactions and provide a perspective on how this methodology has affected the synthesis of complex natural products and potential pharmaceutical agents.I n 2006, 31 new chemical entities were introduced to the world pharmaceutical market and 2,075 molecules were in phase I or II of clinical development 1 . The majority of these were smallmolecule (relative molecular mass ,1,000) organic compounds 2 . As knowledge about the specific interactions of drugs in vivo increases, often so does the structural complexity of new drug targets. A major obstacle to the development of such drugs is the difficulty associated with synthesizing large quantities in an economical fashion, because complex multi-step syntheses are usually required. In the general media, it is often overlooked that the accessibility of the components required for these new treatments will often govern their eventual success or failure. Likewise, a design element of any pharmaceutical agent is the expectation that the target compounds can be made economically. Therefore, new strategies for synthesis can become enabling technologies, making available new targets and materials that would have been previously out of range. For example, new methodologies such as metal-catalysed crosscoupling 3 and olefin metathesis 4-6 have rapidly become central transformations in the synthesis of new pharmaceutical agents. Selective C-H functionalization is a class of reactions that could lead to a paradigm shift in organic synthesis, relying on selective modification of ubiquitous C-H bonds of organic compounds instead of the standard approach of conducting transformations on pre-existing functional groups. The reactive sites in each type of transformation are very different, as illustrated in Fig. 1.The many opportunities associated with C-H functionalization has made this field an active area of research. Organometallic chemists have focused much attention on developing 'C-H activation' strategies, whereby a highly reactive metal complex inserts into a C-H bond, activating the system for subsequent transformations 7-9 . One of the major challenges associated with this chemistry has been to render it catalytic in the metal complex 10 . A partial solution to this problem has been to use neighbouring functionality to direct less reactive metal complexes to the site for functionalization. Numerous reviews have been written about this method for C-H functionalization [11][12][13][14][15][16][17] . Here, however, we highlight another approach, in which a divalent c...

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Section: C-h Functionalization By Metal Nitrenoidsmentioning

confidence: 99%

Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion

Davies

Manning

2008

Nature

2,174

812

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“…The sulfamate 10, which was prepared from the commercially available δ-N-tertbutoxycarbonyl (Boc)-α-N-benzyloxycarbonyl (Cbz)-L-ornithine (7) in 66% yield over 3 steps, was treated with 10 mol% bis[rhodium(α,α,α′,α′-tetramethyl-1,3-benzenedi-propionic acid)] (Rh 2 (esp) 2 ) catalyst, 26) in the presence of PhI(OAc) 2 and MgO in refluxing CH 2 Cl 2 for 1.5 h, and the desired oxathiazinane derivatives 11a and b were obtained in 47% yield (11a : 11b=1 : 2). After 11a was converted to the S-methylisothiourea derivative 12, construction of the cyclic guanidine skeleton was performed through cyclization promoted by HgBr 2 and the following desulfonylation upon acetolysis of the oxathiazinane ring gave 13 in 82% yield over 2 steps.…”

Section: Medicinal and Bioorganic Chemistry Of Nucleosides And Nucleomentioning

confidence: 99%

Synthesis and Medicinal Chemistry of Muraymycins, Nucleoside Antibiotics

Katsuyama

Ichikawa

2018

CHEMICAL & PHARMACEUTICAL BULLETIN

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Muraymycins, isolated from a culture broth of Streptomyces sp., are members of a class of naturally occurring nucleoside antibiotics. They are strong inhibitors of the phospho-MurNAc-pentapeptide translocase (MraY), which is responsible for the peptidoglycan biosynthesis. Since MraY is an essential enzyme among bacteria, muraymycins are expected to be a novel antibacterial agent. In this review, our efforts to synthesize muraymycin D2, simplify the chemical structure, improve antibacterial spectrum, and solve the X-ray crystal structure of the muraymycin D2/MraY complex are described.

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“…首先, 在 LDA 存在下, 2-甲基氯化苄和异丁腈在-78 ℃下反应 [13] , 得到 2-甲基-1-(2-甲基苯基)-2-丁腈 (3a), 产率为 89%; 接着, 在氢氧化钾作用下加热水解 8 h, 生成 2-甲基-1-(2-甲基苯基)-2-丁酸(4a), 产率高达 92%. 接下来, 羧酸 4a 在叠氮磷酸二苯酯(DPPA)、三乙胺以及苄醇的作用下发生 Curtius 重排 [14～17] , 最终以 71%的产率得到了化合物 5a.…”

Section: 结果与讨论unclassified

An Efficient Method for the Synthesis of 2-Methyl-1-substituted-phenyl-2-propylamines

朱兰平¹,

赵帅²,

仓志鹏³

et al. 2018

Chin. J. Org. Chem.

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2-Methyl-1-substituted-phenyl-2-propylamines are key intermediates for synthesizing the β 2 adrenoceptor agonists. A series of 2-methyl-1-substituted-phenyl-2-propylamines have been synthesized starting from substituted benzyl chlorides. Isobutyronitrile was alkylated with benzyl chloride, and the resulting 2-methyl-1-aryl-2-butylcynide was hydrolyzed to give the corresponding acid. Curtius rearrangement of the acid and catalytic hydrolgenation of the resulting Cbz-protected amine afforded the title compound. The method is simple and safe to operate, the raw materials are readily available and the overall yields are satisfactory. This method is suitable for the synthesis of 2-methyl-2-(2-methylphenyl)-phenyl-2-propylamine and various kinds of derivatives.

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Expanding the Scope of C−H Amination through Catalyst Design

Cited by 622 publications

References 17 publications

Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion

Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion

Synthesis and Medicinal Chemistry of Muraymycins, Nucleoside Antibiotics

An Efficient Method for the Synthesis of 2-Methyl-1-substituted-phenyl-2-propylamines

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