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14 Dec 09:30

Transition-Metal-Catalyzed Selective Functionalization of C(sp3)−H Bonds in Natural Products

by Rashad R Karimov, John F. Hartwig

Abstract

Direct functionalization of natural products is important for studying the structure–activity and structure–property relationships of these molecules. Recent advances in the transition-metal-catalyzed functionalization of C(sp3)−H bonds, the most abundant yet inert bonds in natural products, have allowed natural product derivatives to be created selectively. Strategies to achieve such transformation are reviewed.

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Direct derivatization: Direct functionalization of natural products is important for studying their structure–activity and structure–property relationships. Recent advances in the transition-metal-catalyzed functionalization of C(sp3)−H bonds have shown that natural product derivatives can be selectively produced. Strategies for achieving such transformations are discussed.

30 Nov 11:10

Chemoselective One-Pot Synthesis of Functionalized Amino-azaheterocycles Enabled by COware

by Thomas A. Clohessy, Alastair Roberts, Eric S. Manas, Vipulkumar K. Patel, Niall A. Anderson and Allan J. B. Watson

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Organic Letters
DOI: 10.1021/acs.orglett.7b03214
15 Nov 12:28

Lewis acid enhancement by hydrogen-bond donors for asymmetric catalysis

by Banik, S. M., Levina, A., Hyde, A. M., Jacobsen, E. N.

Small-molecule dual hydrogen-bond (H-bond) donors such as ureas, thioureas, squaramides, and guanidinium ions enjoy widespread use as effective catalysts for promoting a variety of enantioselective reactions. However, these catalysts are only weakly acidic and therefore require highly reactive electrophilic substrates to be effective. We introduce here a mode of catalytic activity with chiral H-bond donors that enables enantioselective reactions of relatively unreactive electrophiles. Squaramides are shown to interact with silyl triflates by binding the triflate counterion to form a stable, yet highly Lewis acidic, complex. The silyl triflate-chiral squaramide combination promotes the generation of oxocarbenium intermediates from acetal substrates at low temperatures. Enantioselectivity in nucleophile additions to the cationic intermediates is then controlled through a network of noncovalent interactions between the squaramide catalyst and the oxocarbenium triflate.

24 Oct 05:42

MOF-derived cobalt nanoparticles catalyze a general synthesis of amines

by Jagadeesh, R. V., Murugesan, K., Alshammari, A. S., Neumann, H., Pohl, M.-M., Radnik, J., Beller, M.

The development of base metal catalysts for the synthesis of pharmaceutically relevant compounds remains an important goal of chemical research. Here, we report that cobalt nanoparticles encapsulated by a graphitic shell are broadly effective reductive amination catalysts. Their convenient and practical preparation entailed template assembly of cobalt-diamine-dicarboxylic acid metal organic frameworks on carbon and subsequent pyrolysis under inert atmosphere. The resulting stable and reusable catalysts were active for synthesis of primary, secondary, tertiary, and N-methylamines (more than 140 examples). The reaction couples easily accessible carbonyl compounds (aldehydes and ketones) with ammonia, amines, or nitro compounds, and molecular hydrogen under industrially viable and scalable conditions, offering cost-effective access to numerous amines, amino acid derivatives, and more complex drug targets.

18 Oct 05:39

Drug Delivery: Too Much Complexity, Not Enough Reproducibility?

by Jean-Christophe Leroux
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“… Drug-delivery research is experiencing a major expansion, however the upsurge in published reports does not correlate with therapeutic advances. Reporting complex systems seems to have prevailed over the desire to treat a disease effectively with a robust and safe formulation. Another important issue is the lack of reproducibility of published findings …” Read more in the Editorial by Jean-Christoph Leroux.

12 Sep 11:18

Proof of concept for continuous enantioselective liquid-liquid extraction in capillary microreactors using 1-octanol as a sustainable solvent

Green Chem., 2017, 19,4334-4343
DOI: 10.1039/C7GC01700F, Paper
Susanti, Tim G. Meinds, Erik B. Pinxterhuis, Boelo Schuur, Johannes G. de Vries, Ben L. Feringa, Jozef G. M. Winkelman, Jun Yue, Hero J. Heeres
Separation of racemates in microreactors using liquid-liquid extraction with 1-octanol as the solvent is successfully demonstrated.
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02 Jan 08:39

Short and Efficient Chemoenzymatic Syntheses of non-Natural (−)-Muscarine and (+)-allo-Muscarine from Cyano-Sugar Precursors Catalyzed by Immobilized Burkholderia cepacia Lipase

by Alejandro Carnero, Yogesh S. Sanghvi, Vicente Gotor, Susana Fernández, Miguel Ferrero

Abstract

Enantiopure (2R)-configured non-natural (−)-muscarine and (+)-allo-muscarine were efficiently synthesized by a chemoenzymatic approach from an easily accessible cyano-sugar available on a large-scale. The key enzymatic hydrolysis step was accomplished by immobilized Burkholderia cepacia lipase (also known as Pseudomonas cepacia lipase, PSL-IM). The PSL-IM-mediated regioselective hydrolysis of the 5-O-toluoyl ester group in α- and β-cyano-sugars, furnished 3-O-toluoyl-α-cyano-sugar and 3-O-toluoyl-β-cyano-sugar, respectively, with total selectivity and in excellent yields. To demonstrate the industrial utility of this method, 3-O-toluoyl-β-cyano-sugar was synthesized on a 10 g scale using PSL-IM and the catalyst was reused. A key feature of the synthesis route described herein is the simultaneous hydrogenolysis of a tosyl group, reduction of a nitrile and deprotection of a toluoyl group using LiAlH4 in a one-pot procedure. This study offers a green protocol for synthesis of two muscarine derivatives in high yields employing a concise four-step strategy.

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14 Nov 08:09

José Barluenga (1940–2016)

by José M. González, Kilian Muñiz
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José Barluenga, emeritus professor at the University of Oviedo, passed away on September 7, 2016. Barluenga was one of the leading Spanish chemists of his generation, with research interests including metal-mediated activation of alkenes and alkynes, β-functionalized organolithium compounds, iodination reactions, asymmetric Diels–Alder reactions, carbene complexes, and cross-coupling reactions.

02 Sep 12:05

The synthesis of substituted phosphathiahelicenes via regioselective bromination of a preformed helical scaffold: a new approach to modular ligands for enantioselective gold-catalysis

Chem. Commun., 2016, 52,10984-10987
DOI: 10.1039/C6CC04765C, Communication
Paul Aillard, Davide Dova, Valentin Magne, Pascal Retailleau, Silvia Cauteruccio, Emanuela Licandro, Arnaud Voituriez, Angela Marinetti
New substituted phosphathiahelicenes have been synthesized and used as ligands in gold(I)-catalyzed [4+2] cyclizations of 1,6-enynes (up to 91% ee).
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02 Sep 11:46

Gold-Catalyzed Domino Synthesis of Functionalized Benzofurans and Tetracyclic Isochromans via Formal Carboalkoxylation

by Tomoyuki Obata, Sho Suzuki, Asuka Nakagawa, Ryota Kajihara, Keiichi Noguchi and Akio Saito

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Organic Letters
DOI: 10.1021/acs.orglett.6b02159
14 Jun 09:11

Enantioselective Intramolecular C−H Insertion of Donor- and Donor/Donor-Carbenes by a Nondiazo Approach

by Dong Zhu, Jun Ma, Kui Luo, Hongguang Fu, Li Zhang, Shifa Zhu

Abstract

The first enantioselective intramolecular C−H insertion and cyclopropanation reactions of donor- and donor/donor-carbenes by a nondiazo approach are reported. The reactions were conducted in a one-pot manner without slow addition and provided the desired dihydroindole, dihydrobenzofuran, tetrahydrofuran, and tetrahydropyrrole derivatives with up to 99 % ee and 100 % atom efficiency.

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Generous donor: Enantioselective intramolecular C−H insertion and cyclopropanation reactions of donor- and donor/donor-carbenes by a nondiazo approach are reported. The reactions were conducted in a one-pot manner without slow addition and provided the desired dihydroindole, dihydrobenzofuran, tetrahydrofuran, and tetrahydropyrrole derivatives with up to 99 % ee.

01 Jun 07:59

Generalization of the Copper to Late-Transition-Metal Transmetallation to Carbenes beyond N-Heterocyclic Carbenes

by Yannick D. Bidal, Orlando Santoro, Mohand Melaimi, David B. Cordes, Alexandra M. Z. Slawin, Guy Bertrand, Catherine S. J. Cazin

Abstract

Carbene transition-metal complexes have become a prevalent family of catalysts enabling numerous organic transformations. Their facile synthetic access is a matter of great importance. To this end, the CuI-NHC transfer methodology has emerged as a powerful alternative presenting attractive advantages over other methods. Herein, we report the remarkable ability of copper to transfer not only NHCs but also other types of carbenes such as abnormal NHCs (aNHCs), cyclic (alkyl)(amino)carbenes (CAACs), and mesoionic carbenes (MICs) to various transition metal precursors.

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Copper to carbene made easy! The NHC-CuI transmetallation reaction is expanded to Group 9 metals, and generalized to other carbenes such as MICs, aNHCs, and CAACs to generate a library of transition-metal complexes. Since all copper-complex precursors are made by direct metallation of easy-to-handle carbene conjugate acids with copper oxide, the methodology reported here allows for the preparation of a variety of carbene complexes without the use of highly sensitive reagents.

03 Mar 08:28

Expansion of the Concept of Nonlinear Effects in Catalytic Reactions Beyond Asymmetric Catalysis

by Robert Pollice, Michael Schnürch

Abstract

The observation and investigation of nonlinear effects in catalytic reactions provides valuable mechanistic insight. However, the applicability of this method was, until now, limited to molecules possessing chirality and therefore to asymmetric synthesis. The concept of nonlinear effects is expanded to catalytic reactions beyond asymmetric catalysis by using derivatives instead of enantiomers and by considering rates instead of enantiomeric excess. Additionally, its systematic application to investigate the mechanism of catalytic reactions is presented. By exceeding the limitation to asymmetric reactions, the study of nonlinear effects can become a general tool to elucidate reaction mechanisms.

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Escaping asymmetry: The concept of nonlinear effects is expanded from asymmetric catalysis to catalytic reactions in general by investigating reaction rates instead of enantiomeric purity and using derivatives instead of enantiomers.

24 Feb 08:29

Lewis Acid Triggered Regioselective Magnesiation and Zincation of Uracils, Uridines, and Cytidines

by Lydia Klier, Eider Aranzamendi, Dorothée Ziegler, Johannes Nickel, Konstantin Karaghiosoff, Thomas Carell and Paul Knochel

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Organic Letters
DOI: 10.1021/acs.orglett.6b00190
23 Feb 15:57

Copper-catalyzed borylative coupling of vinylazaarenes and N-Boc imines

Chem. Commun., 2016, 52,3770-3772
DOI: 10.1039/C6CC00603E, Communication
Joshua J. Smith, Daniel Best, Hon Wai Lam
Diastereoselective Cu-catalyzed three-component couplings of vinylazaarenes, B2(pin)2, and N-Boc imines are described.
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23 Feb 15:49

1,4-Bis-Dipp/Mes-1,2,4-Triazolylidenes: Carbene Catalysts That Efficiently Overcome Steric Hindrance in the Redox Esterification of α- and β-Substituted α,β-Enals

by Veera Reddy Yatham, Wacharee Harnying, Darius Kootz, Jörg-M. Neudörfl, Nils E. Schlörer and Albrecht Berkessel

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Journal of the American Chemical Society
DOI: 10.1021/jacs.5b11796
18 Feb 12:32

σ-Hole Bond vs π-Hole Bond: A Comparison Based on Halogen Bond

by Hui Wang, Weizhou Wang and Wei Jun Jin

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Chemical Reviews
DOI: 10.1021/acs.chemrev.5b00527
10 Feb 06:52

Oxy-Allyl Cation Catalysis: An Enantioselective Electrophilic Activation Mode

by Chun Liu, E. Zachary Oblak, Mark N. Vander Wal, Andrew K. Dilger, Danielle K. Almstead and David W. C. MacMillan

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Journal of the American Chemical Society
DOI: 10.1021/jacs.5b13041
28 Jan 14:59

Chromatographic NMR Spectroscopy with Hollow Silica Spheres

by Tania González-García, Tommaso Margola, Adriano Silvagni, Fabrizio Mancin, Federico Rastrelli

Abstract

The use of micrometric hollow silica spheres is described as a strategy to reduce magnetic field inhomogeneities in the context of NMR chromatography. When employed as a stationary phase, hollow silica microspheres allow the use of common solution-state NMR instruments to measure the diffusion coefficient perturbation induced by the interaction of the analytes with the silica surface.

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A (w)hole lot better: Hollow silica microspheres made possible the use of solution-state NMR instruments to analyze mixtures of small molecules by chromatographic NMR spectroscopy (see picture). The silica microspheres clearly provide major advantages over conventional stationary phases.

22 Jan 12:44

Improved Second Generation Iron Pincer Complexes for Effective Ester Hydrogenation

by Saravanakumar Elangovan, Bianca Wendt, Christoph Topf, Stephan Bachmann, Michelangelo Scalone, Anke Spannenberg, Haijun Jiao, Wolfgang Baumann, Kathrin Junge, Matthias Beller

Abstract

Hydrogenation of esters to alcohols with a well-defined iron iPr2PNP pincer complex has been recently reported by us and other groups. We now introduce a novel and sterically less hindered Et2PNP congener that provides superior catalytic activity in the hydrogenation of various carboxylic acid esters and lactones compared to the known complex. Successful hydrogenation proceeds under relatively mild conditions (60 °C) with lower catalyst loadings.

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22 Jan 12:35

A Sequential Homologation of Alkynes and Aldehydes for Chain Elongation with Optional 13C-Labeling

by Andreas Brunner, Lukas Hintermann

Abstract

Terminal alkynes (RCCH) are homologated by a sequence of ruthenium-catalyzed anti-Markovnikov hydration of alkyne to aldehyde (RCH2CHO), followed by Bestmann–Ohira alkynylation of aldehyde to chain-elongated alkyne (RCH2CCH). Inverting the sequence by starting from aldehyde brings about the reciprocal homologation of aldehydes instead. The use of 13C-labeled Bestmann–Ohira reagent (dimethyl ((1-13C)-1-diazo-2-oxopropyl)phosphonate) for alkynylation provides straightforward access to singly or, through additional homologation, multiply 13C-labeled alkynes. The labeled alkynes serve as synthetic platform for accessing a multitude of specifically 13C-labeled products. Terminal alkynes with one or two 13C-labels in the alkyne unit have been submitted to alkyne–azide click reactions; the copper-catalyzed version (CuAAC) was found to display a regioselectivity of >50 000:1 for the 1,4- over the 1,5-triazine isomer, as shown analytically by 13C NMR spectroscopy.

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Really Stretching it: “True” homologations for either terminal alkynes or aldehydes are provided by a sequence of ruthenium-catalyzed anti-Markovnikov hydration of terminal alkynes to aldehydes, followed by Bestmann–Ohira alkynylation of aldehydes to alkynes (see scheme). The reaction opens a general access to 13C-labeled linear targets, which, in the case of alkynes, can serve as starting materials for alkyne–azide “13Click” reactions.

20 Jan 10:28

Asymmetric addition of [small alpha]-branched cyclic ketones to allenamides catalyzed by a chiral phosphoric acid

Chem. Sci., 2016, 7,2653-2656
DOI: 10.1039/C5SC04202J, Edge Article
Open Access Open Access
Creative Commons Licence&nbsp This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Xiaoyu Yang, F. Dean Toste
Asymmetric addition of unactivated [small alpha]-branched cyclic ketones to allenamides catalyzed by a chiral phosphoric acid catalyst, generates an all-carbon quaternary stereocenter with broad substrate scope and high enantioselectivity.
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19 Jan 16:15

Au-Catalysed oxidative cyclisation

Chem. Soc. Rev., 2016, 45,4448-4458
DOI: 10.1039/C5CS00887E, Tutorial Review
Zhitong Zheng, Zhixun Wang, Youliang Wang, Liming Zhang
This review discusses the two main strategies of oxidative gold catalysis and their applications in developing valuable synthetic transformations.
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19 Jan 10:07

Direct Synthesis of Primary Amines via Ruthenium-Catalysed Amination of Ketones with Ammonia and Hydrogen

by Joan Gallardo-Donaire, Martin Ernst, Oliver Trapp, Thomas Schaub

Abstract

A highly selective reductive amination of ketones to primary amines with ammonia and hydrogen using a simple ruthenium catalyst has been developed. The protocol described constitutes an efficient and direct atom-economical approach en route to α-methylbenzylamine derivatives in good to high yields. The presence of catalytic amounts of aluminum triflate turned out to be crucial for achieving high conversion towards primary amines.

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18 Jan 10:55

Sulfonamide-directed gold-catalyzed [2+2+2]-cycloadditions of nitriles with two discrete ynamides to construct 2,4-diaminopyridine cores

Chem. Commun., 2016, 52,3187-3190
DOI: 10.1039/C5CC09688J, Communication
Yu-Ling Chen, Pankaj Sharma, Rai-Shung Liu
Gold-catalyzed [2+2+2]-cycloadditions of two discrete ynamides and one nitrile afford 2,4-diaminopyridine derivatives; our mechanistic analysis reveals that the reaction chemoselectivity is affected by the types of sulfonamides.
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15 Jan 07:56

Practical Direct α-Arylation of Cyclopentanones by Palladium/Enamine Cooperative Catalysis

by Yan Xu, Tianshun Su, Zhongxing Huang, Guangbin Dong

Abstract

Direct arylation of cyclopentanones has been a long-standing challenge because of competitive self-aldol condensation and multiple arylations. Reported herein is a direct mono-α-C[BOND]H arylation of cyclopentanones with aryl bromides which is enabled by palladium/amine cooperative catalysis. This method is scalable and chemoselective with broad functional-group tolerance. Application to controlled sequential arylation of cyclopentanones has been also demonstrated.

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Be direct: A direct α-C[BOND]H arylation of normal cyclopentanones with aryl bromides, enabled by palladium/amine cooperative catalysis, features an exceptionally high selectivity for monoarylation, use of readily available starting materials, good scalability, and broad functional-group tolerance.

13 Jan 10:46

Donor–Acceptor Fluorophores for Visible-Light-Promoted Organic Synthesis: Photoredox/Ni Dual Catalytic C(sp3)–C(sp2) Cross-Coupling

by Jian Luo and Jian Zhang

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ACS Catalysis
DOI: 10.1021/acscatal.5b02204
11 Jan 08:08

Advanced Synthesis & Catalysis after 15 Years: Challenges and New Opportunities for Synthetic Science

by Eric N. Jacobsen
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11 Jan 08:02

Gold(I) operational in synergistic catalysis for the intermolecular [small alpha]-addition reaction of aldehydes across allenamides

Chem. Commun., 2016, 52,2905-2908
DOI: 10.1039/C5CC09529H, Communication
Alberto Ballesteros, Pablo Moran-Poladura, Jose M. Gonzalez
A synergistic approach to the catalytic intermolecular [small alpha]-addition of aldehydes across allenamides using gold(I) and proline derivatives.
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11 Jan 08:02

Synergistic gold and enamine catalysis: intermolecular [small alpha]-alkylation of aldehydes with allenamides

Chem. Commun., 2016, 52,2909-2912
DOI: 10.1039/C5CC09533F, Communication
Jaime Fernandez-Casado, Ronald Nelson, Jose L. Mascarenas, Fernando Lopez
Aldehydes can be [small alpha]-alkylated with allenamides by the combined action of an organocatalyst and a gold complex.
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