- Palladium and Nickel Catalyzed Suzuki Cross-Coupling with Alkyl Fluorides
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Suzuki cross-coupling of benzylic and unactivated aliphatic fluorides with aryl- and alkenylboronic acids has been achieved via mechanistically distinct Pd and Ni catalyzed pathways that outperform competing protodeboronation, β-hydride elimination, and h
- Balaraman, Kaluvu,Wolf, Christian
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supporting information
p. 8994 - 8999
(2021/11/20)
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- Radical Chain Reduction via Carbon Dioxide Radical Anion (CO2?-)
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We developed an effective method for reductive radical formation that utilizes the radical anion of carbon dioxide (CO2?-) as a powerful single electron reductant. Through a polarity matched hydrogen atom transfer (HAT) between an electrophilic radical and a formate salt, CO2?- formation occurs as a key element in a new radical chain reaction. Here, radical chain initiation can be performed through photochemical or thermal means, and we illustrate the ability of this approach to accomplish reductive activation of a range of substrate classes. Specifically, we employed this strategy in the intermolecular hydroarylation of unactivated alkenes with (hetero)aryl chlorides/bromides, radical deamination of arylammonium salts, aliphatic ketyl radical formation, and sulfonamide cleavage. We show that the reactivity of CO2?- with electron-poor olefins results in either single electron reduction or alkene hydrocarboxylation, where substrate reduction potentials can be utilized to predict reaction outcome.
- Hendy, Cecilia M.,Smith, Gavin C.,Xu, Zihao,Lian, Tianquan,Jui, Nathan T.
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supporting information
p. 8987 - 8992
(2021/07/01)
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- Anti-Markovnikov hydroarylation of alkenes via polysulfide anion photocatalysis
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A protocol for anti-Markovnikov hydroarylation of alkenes with aryl halides has been developed using polysulfide anions as photocatalysts in the presence of the Hantzsch ester and water under irradiation with visible light.
- Chiba, Shunsuke,Li, Haoyu,Liu, Yuliang
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supporting information
p. 6264 - 6267
(2021/07/02)
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- Synthesis of Fingolimod Employing Regioselective Aziridine Ring-Opening Reaction as a Key Step
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An efficient and scalable synthesis of the immunomodulating drug fingolimod hydrochloride has been developed with the aziridine regioselective ring-opening reaction as a key step. This manuscript describes design, detailed synthetic route scouting, and optimization study of the aziridine ring-opening reaction. As a starting material for the polar part of the fingolimod molecule, cheap, common, and widely commercially available tris(hydroxymethyl)aminomethane was used. n-Octyl group was introduced into the molecule either via Kumada or Negishi cross-couplings, or alternatively by Sonogashira cross-coupling followed by hydrogenation. The final step consists of a one-pot acidic deprotection both of the acetonide and Boc group, providing thus highly pure fingolimod hydrochloride from the crude reaction mixture directly. The described process is highly effective, is industrially applicable, and has been successfully applied to 500 g scales of the target product.
- Cinibulk, Josef,Doubsky, Jan,Klvaňa, Robert,Rádl, Stanislav
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- Nickel-Catalyzed Cross-Electrophile Coupling of Aryl Chlorides with Primary Alkyl Chlorides
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Alkyl chlorides and aryl chlorides are among the most abundant and stable carbon electrophiles. Although their coupling with carbon nucleophiles is well developed, the cross-electrophile coupling of aryl chlorides with alkyl chlorides has remained a chall
- Gilbert, Michael M.,Goldfogel, Matthew J.,Kim, Seoyoung,Weix, Daniel J.
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supporting information
p. 9902 - 9907
(2020/06/27)
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- Esterification of aryl/alkyl acids catalysed by n-bromosuccinimide under mild reaction conditions
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N-halosuccinimides (NXSs) are well-known to be convenient, easily manipulable and low-priced halogenation reagents in organic synthesis. In the present work, N-bromosuccinimide (NBS) has been promoted as the most efficient and selective catalyst among the NXSs in the reaction of direct esterification of aryl and alkyl carboxylic acids. Comprehensive esterification of substituted benzoic acids, mono-, di- and tri-carboxy alkyl derivatives has been performed under neat reaction conditions. The method is metal-free, air- and moisture-tolerant, allowing for a simple synthetic and isolation procedure as well as the large-scale synthesis of aromatic and alkyl esters with yields up to 100%. Protocol for the recycling of the catalyst has been proposed.
- ?ebular, Klara,Bo?i?, Bojan ?.,Stavber, Stojan
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- Nickel-Catalyzed Reductive Cross-Coupling of Aryl Halides with Monofluoroalkyl Halides for Late-Stage Monofluoroalkylation
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A combinatorial nickel-catalyzed monofluoroalkylation of aryl halides with unactivated fluoroalkyl halides by reductive cross-coupling has been developed. This method demonstrated high efficiency, mild conditions, and excellent functional-group tolerance, thus enabling the late-stage monofluoroalkylation of diverse drugs. The key to success was the combination of diverse readily available bidentate and monodentate pyridine-type nitrogen ligands with nickel, which in situ generated a variety of readily tunable catalysts to promote fluoroalkylation with broad scope with respect to both coupling partners. This combinatorial catalysis strategy offers a solution for nickel-catalyzed reductive cross-coupling reactions and provides an efficient way to synthesize fluoroalkylated druglike molecules for drug discovery.
- Sheng, Jie,Ni, Hui-Qi,Zhang, Hao-Ran,Zhang, Kai-Fan,Wang, Yi-Ning,Wang, Xi-Sheng
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supporting information
p. 7634 - 7639
(2018/06/26)
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- Potentiation of the fosmidomycin analogue FR 900098 with substituted 2-oxazolines against Francisella novicida
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A library of 33 compounds was screened for potentiation of the antibiotic FR 900098 against the Francisella tularensis surrogate Francisella novicida. From the screen a highly potent 2-oxazoline adjuvant was discovered capable of potentiating FR 900098 with a 1000-fold reduction in MIC against the Francisella sub-species F. novicida and F. philomiragia.
- Stephens, Matthew D.,Yodsanit, Nisakorn,Melander, Christian
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p. 1952 - 1956
(2016/10/22)
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- METHOD OF REGIOSELECTIVE SYNTHESIS OF SUBSTITUTED BENZOATES
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A method of synthesis of para-substituted benzoate esters and acids is provided, wherein the para-substituted regioisomer is obtained substantially free of the meta-substituted impurity, the method comprising contacting a coumalate ester or acid and an un activated alkene at elevated temperature in the presence of a metal oxidation catalyst and an oxidant. The metal oxidation catalyst can be palladium, such as palladium on carbon, and the oxidant can be the oxygen gas in ambient air. The reaction can be carlied out without solvent or in high boiling hydrocarbon solvents such as mesitylene. When the un activated alkene is a monosubstituted alkene, yields of at least about 50 or 60% of para-substituted ester and acid products, respectively, are obtained, substantially free of the regioisomelic meta-substituted impurity.
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Page/Page column 11; 18; 19
(2013/03/26)
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- A METHOD FOR THE PREPARATION OF FINGOLIMOD
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The invention relates to a method of preparation of 2-amino-2-[2-(4-octylphenyl)- ethyl]propane-1,3-diol (I), comprising opening of the aziridine ring of the intermediates (LVI) by the treatment with organometallic compounds, preferably the Grignard reage
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Page/Page column 17; 18
(2014/01/08)
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- Preparation of alkylmagnesium reagents from alkenes through hydroboration and boron-magnesium exchange
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Tolerant: Alkylmagnesium reagents can be synthesized from alkenes through a sequence of hydroboration and subsequent boron-magnesium exchange using a method that tolerates different functional groups (see scheme). The resulting alkylmagnesium reagents can be used in carbon-carbon bond forming reactions, such as alkylation reactions or transition-metal-catalyzed cross-coupling reactions. Copyright
- Reichle, Markus A.,Breit, Bernhard
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p. 5730 - 5734
(2012/08/14)
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- A convenient synthesis of the immunosuppressive agent FTY720
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This paper describes a practical synthetic approach to preparation of an immunosuppressant, FTY720. The key steps involve an iron-catalyzed cross-coupling reaction and a Wittig reaction. The advantages of this synthesis include readily available starting
- Feng, Xiangjun,Mei, Yuhua,Luo, Yu,Lu, Wei
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experimental part
p. 161 - 164
(2012/07/03)
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- Low temperature studies of iron-catalyzed cross-coupling of alkyl Grignard reagents with aryl electrophiles
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The title reaction has been studied under low temperature conditions. Coupling with active substrates can be done even at dry ice temperature. Initial rate studies at -25 °C indicate that high concentrations of any reagent can lead to either complete or partial catalyst deactivation. Under strongly reducing conditions, iron seems to form less active complexes that only slowly re-enter the catalytic cycle, possibly through bimolecular coupling of iron(II) complexes. Computational studies support the experimental observations, and indicate that oxidation states below +I cannot be reached by reductive elimination. Copyright
- Kleimark, Jonatan,Larsson, Per-Fredrik,Emamy, Parisa,Hedstroem, Anna,Norrby, Per-Ola
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experimental part
p. 448 - 456
(2012/04/10)
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- Aromatics from pyrones: Para-substituted alkyl benzoates from alkenes, coumalic acid and methyl coumalate
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The Diels-Alder reaction of coumalic acid and methyl coumalate with unactivated alkenes provides only para-substituted adducts in good yield.
- Kraus, George A.,Riley, Sean,Cordes, Travis
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experimental part
p. 2734 - 2736
(2011/11/06)
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- NEW BORANE-AMINE COMPLEXES AND THEIR APPLICATION IN SUZUKI-TYPE CROSS -COUPLING REACTIONS
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The invention relates to new amine complexes of B-organyl-9-borabicyclo[3.3.1]nonanes and to solutions of said complexes. Furthermore, the invention relates to a method of using trialkylborane-amine complexes in Suzuki-type cross-coupling reactions and to a process to form new carbon-carbon bonds in a Suzuki-type cross-coupling reaction with a triorganoborane, which is carried out in the presence of an amine.
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Page/Page column 11
(2009/12/05)
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- Synthesis and biological evaluation of sphingosine kinase substrates as sphingosine-1-phosphate receptor prodrugs
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In the search for bioactive sphingosine 1-phosphate (S1P) receptor ligands, a series of 2-amino-2-heterocyclic-propanols were synthesized. These molecules were discovered to be substrates of human-sphingosine kinases 1 and 2 (SPHK1 and SPHK2). When phosphorylated, the resultant phosphates showed varied activities at the five sphingosine-1-phosphate (S1P) receptors (S1P1-5). Agonism at S1P1 was displayed in vivo by induction of lymphopenia. A stereochemical preference of the quaternary carbon was crucial for phosphorylation by the kinases and alters binding affinities at the S1P receptors. Oxazole and oxadiazole compounds are superior kinase substrates to FTY720, the prototypical prodrug immunomodulator, fingolimod (FTY720). The oxazole-derived structure was the most active for human SPHK2. Imidazole analogues were less active substrates for SPHKs, but more potent and selective agonists of the S1P1 receptor; additionally, the imidazole class of compounds rendered mice lymphopenic.
- Foss Jr., Frank W.,Mathews, Thomas P.,Kharel, Yugesh,Kennedy, Perry C.,Snyder, Ashley H.,Davis, Michael D.,Lynch, Kevin R.,Macdonald, Timothy L.
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experimental part
p. 6123 - 6136
(2009/12/06)
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- Isoxazole derivatives, and their use in liquid-crystalline mixtures
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Isoxazole derivatives of the formula (I) where the symbols and indices have the following meanings, for example: T is X is S or O R1and R2are identical or different and are each hydrogen, F, CN or a straight-chain or branched C1
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- Enantioselective Extraction of Di-O-benzoyltartrate Anion by Ion-Pair Extractant Having Binaphthyl-Unit
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A lipophilic diphosphonium salt 1 having binaphthyl-type axial chirality was developed as a novel ion-pair extractant.By use of (R)-1, (-)-di-O-benzoyltartrate ((-)-DBT) was extracted more effectively than (+)-DBT.The enantioselectivity (α=D(-)
- Ohki, Akira,Miyashita, Ryo,Naka, Kensuke,Maeda, Shigeru
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p. 2714 - 2719
(2007/10/02)
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- Cross-Coupling Reaction of Alkyl- or Arylboronic Acid Esters with Organic Halides Induced by Thallium(I) Salts and Palladium-Catalyst
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The cross-coupling reaction of alkylboronic acid esters with 1-alkenyl- or aryl halides is succesfully catalyzed by PdCl2 (dppf) or Pd(PPh3)4 in the presence of thallium(I) hydroxide or carbonate to give the corresponding alkenes or arenes in good yields.The coupling reaction of arylboronic acid esters with aryl halides under similar conditions to provide biaryls is also described.
- Sato, Makoto,Miyaura, Norio,Suzuki, Akira
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p. 1405 - 1408
(2007/10/02)
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- PALLADIUM-CATALYZED CROSS-COUPLING REACTIONS OF B-ALKYL-9-BBN OF TRIALKYLBORANES WITH ARYL AND 1-ALKENYL HALIDES
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The reactions of trialkylboranes or B-alkyl-9-BBN with aryl and 1-alkenyl halides take place readily in the presence of PdCl2(dppf) and sodium hydroxide or methoxide to afford alkylatad arenes and alkenes in excellent yields.
- Miyaura, Norio,Ishiyama, Tatsuo,Ishikawa, Masako,Suzuki, Akira
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p. 6369 - 6372
(2007/10/02)
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