- Catalytic β C-H amination: Via an imidate radical relay
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The first catalytic strategy to harness imidate radicals for C-H functionalization has been developed. This iodine-catalyzed approach enables β C-H amination of alcohols by an imidate-mediated radical relay. In contrast to our first-generation, (super)stoichiometric protocol, this catalytic method enables faster and more efficient reactivity. Furthermore, lower oxidant concentration affords broader functional group tolerance, including alkenes, alkynes, alcohols, carbonyls, and heteroarenes. Mechanistic experiments interrogating the electronic nature of the key 1,5 H-atom transfer event are included, as well as probes for chemo-, regio-, and stereo-selectivity.
- Stateman, Leah M.,Wappes, Ethan A.,Nakafuku, Kohki M.,Edwards, Kara M.,Nagib, David A.
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p. 2693 - 2699
(2019/03/06)
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- Enantioselective Copper Catalyzed Alkyne-Azide Cycloaddition by Dynamic Kinetic Resolution
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The copper(I) catalyzed alkyne-azide cycloaddition (CuAAC), a click reaction, is one of the most powerful catalytic reactions developed during the last two decades. Conducting CuAAC enantioselectively would add a third dimension to this reaction and would
- Liu, En-Chih,Topczewski, Joseph J.
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supporting information
p. 5135 - 5138
(2019/03/29)
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- Asymmetric Allylic C-H Alkylation via Palladium(II)/ cis-ArSOX Catalysis
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We report the development of Pd(II)/cis-aryl sulfoxide-oxazoline (cis-ArSOX) catalysts for asymmetric C-H alkylation of terminal olefins with a variety of synthetically versatile nucleophiles. The modular, tunable, and oxidatively stable ArSOX scaffold is key to the unprecedented broad scope and high enantioselectivity (37 examples, avg. > 90% ee). Pd(II)/cis-ArSOX is unique in its ability to effect high reactivity and catalyst-controlled diastereoselectivity on the alkylation of aliphatic olefins. We anticipate that this new chiral ligand class will find use in other transition metal catalyzed processes that operate under oxidative conditions.
- Liu, Wei,Ali, Siraj Z.,Ammann, Stephen E.,White, M. Christina
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p. 10658 - 10662
(2018/09/06)
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- Directed β C-H Amination of Alcohols via Radical Relay Chaperones
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A radical-mediated strategy for β C-H amination of alcohols has been developed. This approach employs a radical relay chaperone, which serves as a traceless director that facilitates selective C-H functionalization via 1,5-hydrogen atom transfer (HAT) and enables net incorporation of ammonia at the β carbon of alcohols. The chaperones presented herein enable direct access to imidate radicals, allowing their first use for H atom abstraction. A streamlined protocol enables rapid conversion of alcohols to their β-amino analogs (via in situ conversion of alcohols to imidates, directed C-H amination, and hydrolysis to NH2). Mechanistic experiments indicate HAT is rate-limiting, whereas intramolecular amination is product- and stereo-determining.
- Wappes, Ethan A.,Nakafuku, Kohki M.,Nagib, David A.
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p. 10204 - 10207
(2017/08/10)
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- Diastereoselective and Enantiospecific Synthesis of 1,3-Diamines via 2-Azaallyl Anion Benzylic Ring-Opening of Aziridines
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The 1,3-diamine motif appears in numerous complex molecules, yet there are few methods for the stereoselective construction of this moiety. Herein, we demonstrate a stereocontrolled synthesis of 1,3-diamines, which bear up to three contiguous stereogenic centers, through benzylic ring-opening of aziridines with 2-azaallyl anion nucleophiles. Reactions proceed efficiently (yield up to 95%), diastereoselectively (dr up to >20:1), site selectively, and enantiospecifically to deliver products with differentiated amino groups.
- Li, Kangnan,Weber, Alexandria E.,Tseng, Luke,Malcolmson, Steven J.
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supporting information
p. 4239 - 4242
(2017/08/23)
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- Potent and Selective Inhibitors of Histone Deacetylase-3 Containing Chiral Oxazoline Capping Groups and a N-(2-Aminophenyl)-benzamide Binding Unit
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A novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contains an oxazoline capping group and a N-(2-aminophenyl)-benzamide unit. Among several new inhibitors of this type exhibiting Class I selectivity and potent inhibition of HDAC3-NCoR2, in vitro assays for the inhibition of HDAC1, HDAC2, and HDAC3-NCoR2 by N-(2-aminophenyl)-benzamide 15k gave respective IC50 values of 80, 110, and 6 nM. Weak inhibition of all other HDAC isoforms (HDAC4, 5, 6, 7, and 9: IC50 > 100000 nM; HDAC8: IC50 = 25000 nM; HDAC10: IC50 > 4000 nM; HDAC11: IC50 > 2000 nM) confirmed the Class I selectivity of 15k. 2-Aminoimidazolinyl, 2-thioimidazolinyl, and 2-aminooxazolinyl units were shown to be effective replacements for the pyrimidine ring present in many other 2-(aminophenyl)-benzamides previously reported, but the 2-aminooxazolinyl unit was the most potent in inhibiting HDAC3-NCoR2. Many of the new HDAC inhibitors showed higher solubilities and lower binding to human serum albumin than that of Mocetinostat. Increases in histone H3K9 acetylation in the human cell lines U937 and PC-3 was observed for all three oxazolinyl inhibitors evaluated; those HDAC inhibitors also lowered cyclin E expression in U937 cells but not in PC-3 cells, indicating underlying differences in the mechanisms of action of the inhibitors on those two cell lines.
- Marson, Charles M.,Matthews, Christopher J.,Atkinson, Stephen J.,Lamadema, Nermina,Thomas, N. Shaun B.
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p. 6803 - 6818
(2015/09/22)
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- A general asymmetric synthesis of phenylglycinols
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Hydride reduction and deprotection of siloxymethyl sulfinimines 2 reliably furnished chiral phenylglycinols 1 or 10 in high overall yield and enantiomeric purity.
- Pan, Xingang,Jia, Liangbin,Liu, Xuejian,Ma, Haikuo,Yang, Wenqian,Schwarz, Jacob B.
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p. 329 - 337
(2011/05/17)
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- Formal aromatic C-H insertion for stereoselective isoquinolinone synthesis and studies on mechanistic insights into the C-C bond formation
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(Chemical Equation Presented) Formal aromatic C-H insertion of rhodium(II) carbenoid was intensively investigated to develop a new methodology and probe its mechanism. Contrasting with the previously proposed direct C-H insertion, the mechanism was revealed to be electrophilic aromatic substitution, which was supported by substituent effects on the aromatic ring and a secondary deuterium kinetic isotope effect. Various isoquinolinones were synthesized intramolecularly via six-membered ring formation with high regioand diastereoselectivity, while averting the common Buchner-type reaction. Intermolecularly, dirhodium catalyzed formal aromatic C-H insertion on electron-rich aromatics was also achieved.
- Park, Chan Pil,Nagle, Advait,Cheol, Hwan Yoon,Chen, Chiliu,Kyung, Woon Jung
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supporting information; scheme or table
p. 6231 - 6236
(2009/12/08)
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- 2-Cyanophenyl fused heterocyclic compounds, and compositions and uses thereof
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Fused heterocyclic compounds are provided according to formula 1: where R1, R2, R3, and m are as defined herein. Provided compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, cognitive disorders, anxiety, depression, and others.
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Page/Page column 32
(2008/12/08)
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- PYRID-2-YL FUSED HETEROCYCLIC COMPOUNDS, AND COMPOSITIONS AND USES THEREOF
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Fused heterocyclic compounds are provided according to formula 1a or 1b: where R1, R2, and R3 are as defined herein. Provided compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, cognitive disorders, anxiety, depression, and others.
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Page/Page column 50-51
(2008/12/04)
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- Enantioselective complexation of phenolic crown ethers with chiral aminoethanol derivatives: Effects of substituents of aromatic rings of hosts and guests on complexation
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Optically active azophenolic crown ethers having phenyl groups substituted at the respective para-position were prepared and their association constants with chiral aminoethanol derivatives, including 2-amino-2-phenyl-ethanols having an electron-donating or an electron-withdrawing group, were determined in chloroform by means of UV-vis titration methods. The enantioselectivities of these crown ethers are estimated from the ratio of the association constants KR/KS and the effect of aromatic substituents of both hosts and guests on the binding abilities and enantioselectivities is discussed. The structures of the complexes were investigated on the basis of the 1H NMR and UV-vis spectra.
- Hirose, Keiji,Ogasahara, Kazuko,Nishioka, Kazuyuki,Tobe, Yoshito,Naemura, Koichiro
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p. 1984 - 1993
(2007/10/03)
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