- One-Pot Deoxygenation and Substitution of Alcohols Mediated by Sulfuryl Fluoride
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Sulfuryl fluoride is a valuable reagent for the one-pot activation and derivatization of aliphatic alcohols, but the highly reactive alkyl fluorosulfate intermediates limit both the types of reactions that can be accessed as well as the scope. Herein, we report the SO2F2-mediated alcohol substitution and deoxygenation method that relies on the conversion of fluorosulfates to alkyl halide intermediates. This strategy allows the expansion of SO2F2-mediated one-pot processes to include radical reactions, where the alkyl halides can also be exploited in the one-pot deoxygenation of primary alcohols under mild conditions (52-95% yield). This strategy can also enhance the scope of substitutions to nucleophiles that are previously incompatible with one-pot SO2F2-mediated alcohol activation and enables substitution of primary and secondary alcohols in 54-95% yield. Chiral secondary alcohols undergo a highly stereospecific (90-98% ee) double nucleophilic displacement with an overall retention of configuration.
- Epifanov, Maxim,Mo, Jia Yi,Dubois, Rudy,Yu, Hao,Sammis, Glenn M.
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p. 3768 - 3777
(2021/03/01)
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- Advances and mechanistic insight on the catalytic Mitsunobu reaction using recyclable azo reagents
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Ethyl 2-arylhydrazinecarboxylates can work as organocatalysts for Mitsunobu reactions because they provide ethyl 2-arylazocarboxylates through aerobic oxidation with a catalytic amount of iron phthalocyanine. First, ethyl 2-(3,4-dichlorophenyl)hydrazinecarboxylate has been identified as a potent catalyst, and the reactivity of the catalytic Mitsunobu reaction was improved through strict optimization of the reaction conditions. Investigation of the catalytic properties of ethyl 2-arylhydrazinecarboxylates and the corresponding azo forms led us to the discovery of a new catalyst, ethyl 2-(4-cyanophenyl)hydrazinecarboxylates, which expanded the scope of substrates. The mechanistic study of the Mitsunobu reaction with these new reagents strongly suggested the formation of betaine intermediates as in typical Mitsunobu reactions. The use of atmospheric oxygen as a sacrificial oxidative agent along with the iron catalyst is convenient and safe from the viewpoint of green chemistry. In addition, thermal analysis of the developed Mitsunobu reagents supports sufficient thermal stability compared with typical azo reagents such as diethyl azodicarboxylate (DEAD). The catalytic system realizes a substantial improvement of the Mitsunobu reaction and will be applicable to practical synthesis.
- Hirose, Daisuke,Gazvoda, Martin,Ko?mrlj, Janez,Taniguchi, Tsuyoshi
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p. 5148 - 5159
(2016/07/29)
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- O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1
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Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a potent sub-micromolar inhibitor of IDO1. Structure-activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications.
- Malachowski, William P.,Winters, Maria,DuHadaway, James B.,Lewis-Ballester, Ariel,Badir, Shorouk,Wai, Jenny,Rahman, Maisha,Sheikh, Eesha,LaLonde, Judith M.,Yeh, Syun-Ru,Prendergast, George C.,Muller, Alexander J.
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p. 564 - 576
(2016/01/09)
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- Recyclable mitsunobu reagents: Catalytic mitsunobu reactions with an iron catalyst and atmospheric oxygen
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Aerobic recycling: A catalytic amount of a hydrazine reagent is sufficient to promote Mitsunobu reactions in the presence of triphenylphosphine, an iron catalyst, and air. The active form of the catalyst, an azo species, can be readily generated by iron-c
- Hirose, Daisuke,Taniguchi, Tsuyoshi,Ishibashi, Hiroyuki
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supporting information
p. 4613 - 4617
(2013/06/04)
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- Remote C-H functionalization: Using the N-O moiety as an atom-economical tether to obtain 1,5- and the rare 1,7-C-H insertions
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(Chemical Equotion Present) Dr. N-O: Rhodium-catalyzed intramolecular C-H insertion with diazocompounds, which are tethered by alkoxyamines, afforded 1,5- and the rare 1,7-insertion products (see scheme; Bn = benzyl). The resulting N-O tether is unaffected under the C-H insertion reaction conditions and it can be readily cleaved or transformed into various functionalities. The reduction of the N-O moiety controls acyclic stereochemistry.
- Wang, Jingxin,Stefane, Bogdan,Jaber, Deana,Smith, Jacqueline A.I.,Vickery, Christopher,Diop, Mouhamed,Sintim, Herman O.
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supporting information; experimental part
p. 3964 - 3968
(2010/09/03)
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- 1-Benzyloxy-4,5-dihydro-1H-imidazol-2-yl-amines, a novel class of NR1/2B subtype selective NMDA receptor antagonists
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Screening of the Roche compound depository led to the identification of (1-benzyloxy-4,5-dihydro-1H-imidazol-2-yl)-butyl amine 4, a structurally novel NR1/2B subtype selective NMDA receptor antagonist. The structure-activity relationships developed in this series resulted in the discovery of a novel class of potent and selective NMDA receptor blockers displaying activity in vivo.
- Alanine, Alexander,Bourson, Anne,Buettelmann, Bernd,Gill, Ramanjit,Heitz, Marie-Paule,Mutel, Vincent,Pinard, Emmanuel,Trube, Gerhard,Wyler, Rene
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p. 3155 - 3159
(2007/10/03)
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- Facile generation of alkoxy radicals from N-alkoxyphthalimides
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N-Alkoxyphthalimides, stable and readily accessible from alcohols and alkyl halides, are found to be very efficient alkoxy radical precursors.
- Kim, Sunggak,Lee, Tai Au,Song, Yukwan
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p. 471 - 472
(2007/10/03)
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