- Dual Nickel- And Photoredox-Catalyzed Reductive Cross-Coupling of Aryl Halides with Dichloromethane via a Radical Process
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The first catalytic strategy to harness a new chloromethane radical from dichloromethane under dual Ni/photoredox catalytic conditions has been developed. Compared with traditional two-electron reductive process associated with metallic reductants, this method via a single-electron approach can proceed under exceptionally mild conditions (visible light, ambient temperature, no strong base) and exhibits complementary reactivity patterns. It affords a broad scope of many functional groups, including alkenyl, which suffers cyclopropanation in previous routes. The diarylmethane-d2 compounds can be readily available with this transformation.
- Xu, Tao,Xu, Wenhao,Zheng, Purui
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supporting information
(2020/11/13)
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- Feedstocks to Pharmacophores: Cu-Catalyzed Oxidative Arylation of Inexpensive Alkylarenes Enabling Direct Access to Diarylalkanes
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A Cu-catalyzed method has been identified for selective oxidative arylation of benzylic C-H bonds with arylboronic esters. The resulting 1,1-diarylalkanes are accessed directly from inexpensive alkylarenes containing primary and secondary benzylic C-H bonds, such as toluene or ethylbenzene. All catalyst components are commercially available at low cost, and the arylboronic esters are either commercially available or easily accessible from the commercially available boronic acids. The potential utility of these methods in medicinal chemistry applications is highlighted.
- Vasilopoulos, Aristidis,Zultanski, Susan L.,Stahl, Shannon S.
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p. 7705 - 7708
(2017/06/20)
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- The conversion of alcohols to halides using a filterable phosphine source
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The conversion of primary and secondary alcohols to chlorides and bromides using 1,2-bis(diphenylphosphino)ethane (diphos) is described. Use of this reagent in lieu of the typical triphenylphosphine-carbontetrahalide complex provides a facile means of purifying the desired halide from the phosphine-oxide byproduct.
- Pollastri, Michael P.,Sagal, John F.,Chang, George
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p. 2459 - 2460
(2007/10/03)
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- Histaprodifens: Synthesis, pharmacological in vitro evaluation, and molecular modeling of a new class of highly active and selective histamine H1-receptor agonists
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A new class of histamine analogues characterized by a 3,3-diphenylpropyl substituent at the 2-position of the imidazole nucleus has been prepared outgoing from 4,4-diphenylbutyronitrile (4b) via cyclization of the corresponding methyl imidate 5b with 2-oxo-4-phthalimido-1-butyl acetate or 2-oxo-1,4-butandiol in liquid ammonia, followed by standard reactions. The title compounds displayed partial agonism on contractile H1 receptors of the guinea-pig ileum and endothelium-denuded aorta, respectively, except 10 (histaprodifen; 2-[2-(3,3-diphenylpropyl)1H-imidazol-4-yl]ethanamine) which was a full agonist in the ileum assay. While 10 was equipotent with histamine (1), methylhistaprodifen (13) and dimethylhistaprodifen (14) exceeded the functional potency of 1 by a factor of 3-5 (13) and 2-3 (14). Compounds 10 and 13-17 relaxed precontracted rat aortic rings (intact endothelium) with relative potencies of 3.3- up to 28-fold (compared with 1), displaying partial agonism as well. Agonist effects were sensitive to blockade by the selective H1-receptor antagonist mepyramine (pA2 ? 9 (guinea-pig) and pA2 ? 8 (rat aorta)). The affinity of 10 and 13-17 for guinea-pig H1 receptors increased 20- to 100-fold compared with 1. Two lower homologues of 10 were weak partial H1-receptor agonists while two higher homologues of 10 were silent antagonists endowed with micromolar affinity for rat and guinea-pig H1 receptors. In functional selectivity experiments, 10, 13, and 14 did not stimulate H2, H3, and several other neurotransmitter receptors. They displayed only low to moderate affinity for these sites (pA2 1 receptor were studied using molecular dynamics simulations. Remarkable differences were found between the binding modes of 10, 13, and 14 and that of 1. The imidazole ring of 10, 13, and 14 was placed 'upside down' compared with 1, making the interaction of the N(π)-atom with Tyr431 possible. This new orientation was mainly caused by the space filling substitution at the 2-position of the imidazole ring and influenced the location of the protonated N(α)-atom which was positioned more between TM III and TM VI. This orientation can explain both the increased relative potency and the maximum effect of 10, 13, and 14 compared with 1. Compound 13 (methylhistaprodifen; N(α)-methyl-2-[2-(3,3-diphenylpropyl)-1H-imidazol-4- yl]ethanamine) is the most potent histamine H1-receptor agonist reported so far in the literature and may become a valuable tool for the study of physiological and pathophysiological H1-receptor-mediated effects.
- Elz, Sigurd,Kramer, Kai,Pertz, Heinz H.,Detert, Heiner,Ter Laak, Anton M.,Kühne, Ronald,Schunack, Walter
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p. 1071 - 1084
(2007/10/03)
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- Novel reductive Friedel-Crafts alkylation of aromatics catalyzed by indium compounds: Chemoselective utilization of carbonyl moieties as alkylating reagents
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Reductive Friedel-Crafts alkylation of aromatics with ketones or aldehydes was characteristically catalyzed by indium compounds in preference to general catalysts like AlCl3 and BF3, where hydrosilanes would play an important role both as a hydride donor and as a co-catalyst. Chemoselective utilization of ketone moieties as alkylating reagents took place even in the presence of halogen, ester or ether moieties which are very susceptible under traditional Friedel-Crafts conditions. Discussion on a plausible intermediate was carried out by some controlled experiments.
- Miyai, Takashi,Onishi, Yoshiyuki,Baba, Akio
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p. 1017 - 1026
(2007/10/03)
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