- Copper-Catalyzed Transfer Hydrodeuteration of Aryl Alkenes with Quantitative Isotopomer Purity Analysis by Molecular Rotational Resonance Spectroscopy
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A copper-catalyzed alkene transfer hydrodeuteration reaction that selectively incorporates one hydrogen and one deuterium atom across an aryl alkene is described. The transfer hydrodeuteration protocol is selective across a variety of internal and terminal alkenes and is also demonstrated on an alkene-containing complex natural product analog. Beyond using 1H, 2H, and 13C NMR analysis to measure reaction selectivity, six transfer hydrodeuteration products were analyzed by molecular rotational resonance (MRR) spectroscopy. The application of MRR spectroscopy to the analysis of isotopic impurities in deuteration chemistry is further explored through a measurement methodology that is compatible with high-throughput sample analysis. In the first step, the MRR spectroscopy signatures of all isotopic variants accessible in the reaction chemistry are analyzed using a broadband chirped-pulse Fourier transform microwave spectrometer. With the signatures in hand, measurement scripts are created to quantitatively analyze the sample composition using a commercial cavity enhanced MRR spectrometer. The sample consumption is below 10 mg with analysis times on the order of 10 min using this instrument - both representing order-of-magnitude reduction compared to broadband MRR spectroscopy. To date, these measurements represent the most precise spectroscopic determination of selectivity in a transfer hydrodeuteration reaction and confirm that product regioselectivity ratios of >140:1 are achievable under this mild protocol.
- Alansari, Isabella Y.,Clark, Joseph R.,Holdren, Martin S.,Neill, Justin L.,Pate, Brooks H.,Reyes, Albert,Sloane, Samantha E.,Sonstrom, Reilly E.,Vang, Zoua Pa
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supporting information
p. 7707 - 7718
(2021/06/21)
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- Site-Selective Acceptorless Dehydrogenation of Aliphatics Enabled by Organophotoredox/Cobalt Dual Catalysis
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The value of catalytic dehydrogenation of aliphatics (CDA) in organic synthesis has remained largely underexplored. Known homogeneous CDA systems often require the use of sacrificial hydrogen acceptors (or oxidants), precious metal catalysts, and harsh reaction conditions, thus limiting most existing methods to dehydrogenation of non- or low-functionalized alkanes. Here we describe a visible-light-driven, dual-catalyst system consisting of inexpensive organophotoredox and base-metal catalysts for room-temperature, acceptorless-CDA (Al-CDA). Initiated by photoexited 2-chloroanthraquinone, the process involves H atom transfer (HAT) of aliphatics to form alkyl radicals, which then react with cobaloxime to produce olefins and H2. This operationally simple method enables direct dehydrogenation of readily available chemical feedstocks to diversely functionalized olefins. For example, we demonstrate, for the first time, the oxidant-free desaturation of thioethers and amides to alkenyl sulfides and enamides, respectively. Moreover, the system's exceptional site selectivity and functional group tolerance are illustrated by late-stage dehydrogenation and synthesis of 14 biologically relevant molecules and pharmaceutical ingredients. Mechanistic studies have revealed a dual HAT process and provided insights into the origin of reactivity and site selectivity.
- Zhou, Min-Jie,Zhang, Lei,Liu, Guixia,Xu, Chen,Huang, Zheng
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supporting information
p. 16470 - 16485
(2021/10/20)
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- GLYCOLATE OXIDASE INHIBITORS AND USE THEREOF
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The present invention provides pyrazoles, isoxazoles, isothiazoles, thiadiazoles, and pyridazines according to Formula I as described herein, and pharmaceutically acceptable salts thereof. Pharmaceutical compositions and methods for treating primary hyperoxaluria, type I (PH) and kidney stones are also described.
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Paragraph 0142
(2019/07/17)
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- Combining photoredox and silver catalysis for azidotrifluoromethoxylation of styrenes
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The first example of an azidotrifluoromethoxylation of styrenes has been achieved by synergistic visible-light-mediated photoredox and silver catalysis. Trifluoromethyl arylsulfonate (TFMS) and the Zhdankin reagent were used as the trifluoromethoxylation reagent and the azide source, respectively. A good functional group tolerance and mild reaction conditions of this method are applicable to late-stage azidotrifluoromethoxylation of complex small molecules. Furthermore, the mechanistic investigations indicate the single-electron transfer involved in the reaction.
- Cong, Fei,Wei, Yongliang,Tang, Pingping
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supporting information
p. 4473 - 4476
(2018/05/03)
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- Regioselective Copper-Catalyzed Boracarboxylation of Vinyl Arenes
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Regioselective copper-catalyzed boracarboxylation of vinyl arenes with bis(pinacolato)diboron and carbon dioxide has been achieved. New boron-functionalized α-aryl carboxylic acids, including nonsteroidal anti-inflammatory drugs (NSAIDs), are obtained in moderate to excellent yields. The synthetic utility of the transformation was shown through subsequent derivatization of the carbon-boron bond yielding formal hydroxy- and fluorocarboxylation products as well as anionic difluoroboralactones.
- Butcher, Trevor W.,McClain, Edward J.,Hamilton, Tyler G.,Perrone, Trina M.,Kroner, Kayla M.,Donohoe, Gregory C.,Akhmedov, Novruz G.,Petersen, Jeffrey L.,Popp, Brian V.
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supporting information
p. 6428 - 6431
(2016/12/23)
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- Heck, Sonogashira, and Hiyama reactions catalyzed by palladium nanoparticles stabilized by tris-imidazolium salt
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Palladium nanoparticles, prepared by the hydrogenation of Pd(dba) 2 in the presence of a tris-imidazolium iodide as stabilizer, act as an efficient catalyst for Heck and copper-free Sonogashira reactions with a range of aryl iodides and bromides at 0.2 mol-% Pd loading. Moreover, we describe a convenient protocol for the fluoride-free Hiyama coupling of vinylsilanes with aryl iodides that involves the use of sodium hydroxide as promoter in a methanol/water mixture. Under the developed conditions, one-pot, double Heck and Hiyama-Heck reactions are successfully achieved.
- Planellas, Marc,Moglie, Yanina,Alonso, Francisco,Yus, Miguel,Pleixats, Roser,Shafir, Alexandr
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supporting information
p. 3001 - 3008
(2014/05/20)
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- COMPOUNDS
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Disclosed are compounds that inhibit Lp-PLA2 activity, processes for their preparation, compositions containing them and their use in the treatment of diseases associated with the activity of Lp-PLA2, for example atherosclerosis, Alzheimer's disease, and/or diabetic macular edema.
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Page/Page column 63
(2012/06/30)
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- Gas-phase ion-molecule reaction of alpha-phenylvinyl cation towards substituted benzenes in the environment of an ITMS
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Ion-molecule reactions between the α-phenylvinyl cation (α-PVC) and mono-substituted benzenes have been investigated using a quadrople ion-trap mass spectrometer. The α-PVC, generated by chemical ionization from phenylacetilene, was found to react selectively with mono-substituted benzenes bearing electron withdrawing groups to give the product ions [M + 103] + and the trans-vinylating product ions [M + 25]+. To characterize the reaction products, a combination of collision-induced dissociation, isotope-labeling experiments and model compounds were used. The results indicate, in addition to direct heteroatom alkylation, high extent of ortho attack. We attributed the positional selectivity of the α-PVC to the nature of the substituent on the neutral molecule. In particular, hydroxy and amino groups promoted the alkenylation at ortho position. Copyright
- Begala, Michela,Tocco, Graziella
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experimental part
p. 1115 - 1124
(2012/02/03)
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- ISOXAZOLINES AS INHIBITORS OF FATTY ACID AMIDE HYDROLASE
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The present invention provides isoxazoline FAAH inhibitors of the formula (I): or pharmaceutically acceptable forms thereof, wherein each of G, Ra, Rb, Rc, and Rd are as defined herein. The present invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable excipient. The present invention also provides methods for treating an FAAH-mediated condition comprising administering a therapeutically effective amount of a compound of formula (I), or pharmaceutically acceptable form thereof, to a subject in need thereof.
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Page/Page column 174; 208
(2010/12/18)
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- A mild catalytic oxidation system: Ruthenium porphyrin and 2,6-dichloropyridine n-oxide applied for alkene dihydroxylation
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A new method was developed to transform alkenes into three types of functional molecules, including epoxides, aldehydes and 1,2-diols by using dichlororuthenium(IV) meso-tetrakis(2,6-dichlorophenyl)porphyrin [Ru(IV)(TDCPP)Cl2] as catalyst and 2,6-dichloropyridine N-oxide (Cl2pyNO) as the oxidant, in which the 1,2-diols were afforded via "one-pot" reactions in moderate yields. Copyright
- Hu, Wen-Xiang,Li, Pei-Rong,Jiang, Gaoxi,Che, Chi-Ming,Chen, Jian
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supporting information; experimental part
p. 3190 - 3194
(2011/02/23)
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- Cobalt-catalyzed electrochemical vinylation of aryl halides using vinylic acetates
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The electroreduction of aryl halides (bromides or chlorides) allows the coupling reaction with vinylic acetates, in the presence of 2,2-bipyridine and catalytic amounts of cobalt bromide, leading to styrene derivatives in good yields.
- Gomes, Paulo,Gosmini, Corinne,Périchon, Jacques
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p. 2999 - 3002
(2007/10/03)
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- Pd/P(t-Bu)3: A mild and general catalyst for stille reactions of aryl chlorides and aryl bromides
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Pd/P(t-Bu)3 serves as an unusually reactive catalyst for Stille reactions of aryl chlorides and bromides, providing solutions to a number of long-standing challenges. An unprecedented array of aryl chlorides can be cross-coupled with a range of organotin reagents, including SnBu4. Very hindered biaryls (e.g., tetra-ortho-substituted) can be synthesized, and aryl chlorides can be coupled in the presence of aryl triflates. The method is user-friendly, since a commercially available complex, Pd(P(t-Bu)3)2, is effective. Pd/P(t-Bu)3 also functions as an active catalyst for Stille reactions of aryl bromides, furnishing the first general method for room-temperature cross-couplings.
- Littke, Adam F.,Schwarz, Lothar,Fu, Gregory C.
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p. 6343 - 6348
(2007/10/03)
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- Inhibitors of squalene synthetase and protein farnesyltransferase
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The present invention provides a compound of the formula STR1 which inhibit squalene synthetase and cholesterol biosynthesis and are useful in the treatment of e.g., hyperlipidaemia, atherosclerosis, or fungal infections, processes for the preparation of the compounds of the invention, intermediates useful in these processes, and pharmaceutical compositions containing the compounds.
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- Inhibitors of protein farnesyltransferase and squalene synthase
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The present invention provides a compound of the formula STR1 or a pharmaceutically acceptable salt thereof, which are useful in inhibiting protein farnesyltransferase and the farnesylation of the oncogene protein Ras or inhibiting de novo squalene production resulting in the inhibition of cholesterol biosynthesis, processes for the preparation of the compounds of the invention in addition to intermediates useful in these processes, a pharmaceutical composition, and to methods of using such compounds.
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