- N-Hydroxyphthalimidyl diazoacetate (NHPI-DA): A modular methylene linchpin for the C-H alkylation of indoles
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Despite the extensive studies on the reactions between conventional diazocompounds and indoles, these are still limited by the independent synthesis of the carbene precursors, the specific catalysts, and the required multi-step manipulation of the products. In this work, we explore redox-Active carbenes in the expedited and divergent synthesis of functionalized indoles. NHPI-DA displays unusual efficiency and selectivity to yield insertion products that can be swiftly elaborated into boron and carbon substituents that are particularly problematic in carbene-mediated reactions.
- Chowdhury, Rajdip,Mendoza, Abraham
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supporting information
p. 4532 - 4535
(2021/05/17)
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- Dearomative Indole (3 + 2) Reactions with Azaoxyallyl Cations - New Method for the Synthesis of Pyrroloindolines
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Herein, we report the first examples of the synthesis of pyrroloindolines by means of (3 + 2) dearomative annulation reactions between 3-substituted indoles and highly reactive azaoxyallyl cations. Computational studies using density functional theory (DFT) (B3LYP-D3/6-311G++) support a stepwise reaction pathway in which initial C-C bond formation takes place at C3 of indole, followed by ring closure to give the observed products. Insights gleaned from these calculations indicate that the solvent, either TFE or HFIP, can stabilize the transition state through H-bonding interactions with oxygen of the azaoxyallyl cation and other relevant intermediates, thereby increasing the rates of these reactions.
- DiPoto, Maria C.,Hughes, Russell P.,Wu, Jimmy
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supporting information
p. 14861 - 14864
(2015/12/08)
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- Amide-Functionalized Naphthyridines on a RhII-RhII Platform: Effect of Steric Crowding, Hemilability, and Hydrogen-Bonding Interactions on the Structural Diversity and Catalytic Activity of Dirhodium(II) Complexes
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Ferrocene-amide-functionalized 1,8-naphthyridine (NP) based ligands {[(5,7-dimethyl-1,8-naphthyridin-2-yl)amino]carbonyl}ferrocene (L1H) and {[(3-phenyl-1,8-naphthyridin-2-yl)amino]carbonyl}ferrocene (L2H) have been synthesized. Room-temperature treatment of both the ligands with Rh2(CH3COO)4 produced [Rh2(CH3COO)3(L1)] (1) and [Rh2(CH3COO)3(L2)] (2) as neutral complexes in which the ligands were deprotonated and bound in a tridentate fashion. The steric effect of the ortho-methyl group in L1H and the inertness of the bridging carboxylate groups prevented the incorporation of the second ligand on the {RhII-RhII} unit. The use of the more labile Rh2(CF3COO)4 salt with L1H produced a cis bis-adduct [Rh2(CF3COO)4(L1H)2] (3), whereas L2H resulted in a trans bis-adduct [Rh2(CF3COO)3(L2)(L2H)] (4). Ligand L1H exhibits chelate binding in 3 and L2H forms a bridge-chelate mode in 4. Hydrogen-bonding interactions between the amide hydrogen and carboxylate oxygen atoms play an important role in the formation of these complexes. In the absence of this hydrogen-bonding interaction, both ligands bind axially as evident from the X-ray structure of [Rh2(CH3COO)2(CH3CN)4(L2H)2](BF4)2 (6). However, the axial ligands reorganize at reflux into a bridge-chelate coordination mode and produce [Rh2(CH3COO)2(CH3CN)2(L1H)](BF4)2 (5) and [Rh2(CH3COO)2(L2H)2](BF4)2 (7). Judicious selection of the dirhodium(II) precursors, choice of ligand, and adaptation of the correct reaction conditions affords 7, which features hemilabile amide side arms that occupy sites trans to the Rh-Rh bond. Consequently, this compound exhibits higher catalytic activity for carbene insertion to the C-H bond of substituted indoles by using appropriate diazo compounds, whereas other compounds are far less reactive. Thus, this work demonstrates the utility of steric crowding, hemilability, and hydrogen-bonding functionalities to govern the structure and catalytic efficacyof dirhodium(II,II) compounds.
- Sarkar, Mithun,Daw, Prosenjit,Ghatak, Tapas,Bera, Jitendra K.
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supporting information
p. 16537 - 16549
(2016/02/12)
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- Synthesis and pharmacological evaluation of (indol-3-yl)alkylamides as potent analgesic agents
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A series of (indol-3-yl)alkylamides was synthesized and evaluated for analgesic activity. Two N-(pyridin-4-yl)acetamides, compounds 24 and 25, bearing benzyl or 4-fluorobenzyl moieties in 1-position of indole ring exhibited promising analgesic properties (ED50 = 8.1 and 11 mg/kg p.o., respectively), being as potent as the reference drugs flupirtine (CAS 56995-20-1), ibuprofen (CAS 15687-27-1) and diclofenac (CAS 15307-86-5). The two test compounds were tested for their anti-inflammatory activity by carrageenin-induced edema in rat paw test. 4-Fluorobenzyl derivative 25 whose ID50 was 0.085 ± 0.021 mmol/kg was selected as a lead compound for further pharmacomodulation.
- Fouchard,Marchand,Le Baut,Emig,Nickel
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p. 814 - 824
(2007/10/03)
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- Indole derivatives useful to treat estrogen-related neoplasms and disorders
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The present invention relates to novel indole derivatives useful in down-regulating estrogen receptor expression. Also included are methods for the treatment of neoplasms or of controlling the growth of a neoplasm in a patient afflicted with a neoplastic disease, especially estrogen-dependent neoplasms such as those associated with breast, ovarian and cervical tissue. Another embodiment of the present invention is a method of prophylactically treating a patient at risk of developing a neoplastic disease state. Also provided is a method for treating autoimmune diseases. Also included are pharmaceutical compositions of the novel indole derivatives.
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