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The term organocatalysis describes the acceleration of chemical reactions through the addition of a substoichiometric quantity of an organic compound. The interest in this field has increased spectacularly in the last few years as result of both the novelty of the concept and, more importantly, the fact that the efficiency and selectivity of many organocatalytic reactions meet the standards of established organic reactions. Organocatalytic reactions are becoming powerful tools in the construction of complex molecular skeletons.[1,2]
The following is a selection of recent articles in this field from Angewandte Chemie, Chemistry—A European Journal, European Journal of Organic Chemistry and Advanced Synthesis & Catalysis. It is updated on a daily basis, so stay tuned!
[1] P. I. Dalko, L. Moisan,
Angew. Chem. 2001, 113, 3840; Angew. Chem. Int. Ed. 2001, 40, 3726
Angew. Chem. 2004, 116, 5248; Angew. Chem. Int. Ed. 2004, 43, 5138.
[2] Special issue of Adv. Synth. Catal. 2004, 346, Nr. 9-10.
Gerard Palau-Lluch, Elena Fernández
Building Functionality through Sequential C-B and C-F Bond Formation [Communication]
Feng Shi, Wei Tan, Ren-Yi Zhu, Gui-Juan Xing, Shu-Jiang Tu
Catalytic Asymmetric Five-Component Tandem Reaction: Diastereo- and Enantioselective Synthesis of Densely Functionalized Tetrahydropyridines with Biological Importance [Full Paper]
Xian-Feng Cai, Mu-Wang Chen, Zhi-Shi Ye, Ran-Ning Guo, Lei Shi, Yan-Qin Li, Yong-Gui Zhou
Asymmetric Transfer Hydrogenation of 3-Nitroquinolines: Facile Access to Cyclic Nitro Compounds with Two Contiguous Stereocenters [Communication]
Hi, neighbor! The first organocatalyzed asymmetric transfer hydrogenation of aromatic nitro compounds was successfully developed with up to 99 % ee. The new methodology provides a direct and facile access to enantiopure cyclic nitro compounds with two contiguous stereocenters.
Zhaobin Wang, Zhilong Chen, Jianwei Sun
Catalytic Enantioselective Intermolecular Desymmetrization of 3-Substituted Oxetanes [Communication]
Wring it out: The title reaction proceeds in the presence of chiral Brønsted acid catalysts. This efficient ring-opening process features low catalyst loading, mild reaction conditions, broad functional group compatibility, high enantioselectivity, and the capability to generate chiral quaternary centers. The highly functionalized desymmetrization products are versatile chiral building blocks in organic synthesis.
Angew. Chem. Int. Ed., May 16, 2013, DOI: 10.1002/anie.201300188
Zhilong Chen, Zhaobin Wang, Jianwei Sun
Catalytic Enantioselective Synthesis of Tetrahydroisoquinolines and Their Analogues Bearing a C4 Stereocenter: Formal Synthesis of (+)-(8S,13R)-Cyclocelabenzine [Communication]
A one-pot wonder: 1,2,3,4-Tetrahydroisoquinolines with a C4 stereocenter can be formed by using a one-pot multicomponent chiral-phosphoric-acid-catalyzed transformation of a mixture of oxetane-tethered benzaldehydes, amines, and the dimethyl ester derivative of the Hantzsch ester (see scheme). This transformation can be used to prepare the spermidine alkaloid, (+)-(8S,13R)-cyclocelabenzine.
Atefeh Garzan, Arvind Jaganathan, Nastaran Salehi Marzijarani, Roozbeh Yousefi, Daniel C. Whitehead, James E. Jackson, Babak Borhan
Solvent-Dependent Enantiodivergence in the Chlorocyclization of Unsaturated Carbamates [Full Paper]
Two solvents, two enantiomers: Enantiodivergent hydroquinidine 1,4-phthalazinediyl diether ((DHQD)2PHAL)-catalyzed chlorocyclization of unsaturated carbamates, controlled solely by the choice of solvent, yields oxazolidinones in high enantioselectivity (see scheme; DCDMH=1,3-dichloro-5,5-dimethyl hydantoin). The origin of the observed enantiodivergence is traced back to a solvent-selected entropy–enthalpy balance between pro-R and pro-S pathways that dictates the course of the reaction.
Man-Yi Han, Huai-Zhen Wang, Wan-Kai An, Ju-Ying Jia, Bao-Chun Ma, Yuan Zhang, Wei Wang
A Concise Synthesis of L-Pyrrolysine [Communication]
Organocatalysis: A concise synthesis of L-pyrrolysine has been accomplished in six steps from simple starting materials. The facile synthetic strategy relies on an organocatalytic Michael addition, an efficient amide coupling, and a challenging method for the imine-bond construction (see scheme).
Reiko Nishino, Takumi Furuta, Keizo Kan, Makoto Sato, Masahiro Yamanaka, Takahiro Sasamori, Norihiro Tokitoh, Takeo Kawabata
Investigation of the Carboxylate Position during the Acylation Reaction Catalyzed by Biaryl DMAP Derivatives with an Internal Carboxylate [Communication]
Location of the carboxylate ion: A series of biaryl DMAP catalysts with an internal carboxylate was prepared, and the catalytic activities of the derivatives were evaluated to determine the carboxylate position that most accelerated the DMAP-catalyzed acylation. The carboxylate ion proximal to the pyridine ring in a face-to-face geometry was found to act as an effective general base for the acylation reaction.
Angew. Chem. Int. Ed., May 06, 2013, DOI: 10.1002/anie.201300665
Diego Petruzziello, Marco Stenta, Andrea Mazzanti, Pier Giorgio Cozzi
A Rational Approach Towards a New Ferrocenyl Pyrrolidine for Stereoselective Enamine Catalysis [Communication]
Ironing out the details: Proline and pyrrolidine derivatives (Hayashi–Jørgensen catalysts) are considered “work horses” in organocatalysis. This report describes a new effective ferrocenyl pyrrolidine catalyst able to perform well in benchmark organocatalytic reactions (see figure). The ferrocene moiety controls the conformational space and a simple alkyl group effectively covers a face of the derived enamine. This new framework can find applications in organocatalysis, and in general, in new ligand design.
Utpal Das, Yi-Ru Chen, Yi-Ling Tsai, Wenwei Lin
Organocatalytic Enantioselective Direct Vinylogous Michael Addition of γ-Substituted Butenolides to 3-Aroyl Acrylates and 1,2-Diaroylethylenes [Communication]
Adding value: The direct vinylogous Michael addition of γ-substituted butenolides with a series of 3-aroyl acrylates and 1,2-diaroylethylenes has been demonstrated. This organocatalytic method delivers highly enantio- and diastereomerically pure γ,γ-disubstituted butenolides with adjacent quaternary and tertiary stereocenters (see scheme).
Florian Kniep, Stefan H. Jungbauer, Qi Zhang, Sebastian M. Walter, Severin Schindler, Ingo Schnapperelle, Eberhardt Herdtweck, Stefan M. Huber
Organocatalysis by Neutral Multidentate Halogen-Bond Donors [Communication]
I(n)organocatalysis: Neutral multidentate halogen-bond donors (halogen-based Lewis acids) catalyze the reaction of 1-chloroisochroman with ketene silyl acetals. The organocatalytic activity is linked to the presence (and number as well as orientation) of iodine substituents. As hidden acid catalysis can be ruled out with high probability, this case constitutes strong evidence for halogen-bond based organocatalysis. TBS=tert-butyldimethylsilyl.
Angew. Chem. Int. Ed., May 06, 2013, DOI: 10.1002/anie.201301351
Yujiro Hayashi, Daisuke Sakamoto, Hiroki Shomura, Daisuke Hashizume
Asymmetric Mannich Reaction of α-Keto Imines Catalyzed by Diarylprolinol Silyl Ether [Communication]
Synthetic methods: An asymmetric catalytic, desulfonylative Mannich reaction of α-keto imines with aldehydes, which is catalyzed by diarylprolinol silyl ether 1, was developed. It gave the Mannich product in good yield with excellent anti and enantioselectivity (see scheme).
Alberto Martínez, Matthew J. Webber, Steffen Müller, Benjamin List
Versatile Access to Chiral Indolines by Catalytic Asymmetric Fischer Indolization [Communication]
“Fisching” for complexity: The chiral Brønsted acid (R)-STRIP catalyzes the asymmetric Fischer indolization of a range of monosubstituted cyclopentanones and cyclohexanones to give chiral fused indolines bearing a quaternary stereogenic center at the 3-position. The method has been extended to include substrates bearing a tethered nucleophile, thus allowing for enantioselective indolization/ring-closing cascades to complex propellanes featuring two vicinal quaternary stereocenters.
Angew. Chem. Int. Ed., Apr 29, 2013, DOI: 10.1002/anie.201301618
Haibin Mao, Aijun Lin, Yan Shi, Zhijie Mao, Xuebin Zhu, Weipeng Li, Hongwen Hu, Yixiang Cheng, Chengjian Zhu
Construction of Enantiomerically Enriched Diazo Compounds Using Diazo Esters as Nucleophiles: Chiral Lewis Base Catalysis [Communication]
Amazing diazo: The title reaction leads to highly functionalized diazo compounds in good yields with excellent enantioselectivities (see scheme; Boc=tert-butoxycarbonyl). The utility of the products was demonstrated by the rapid synthesis of a number of optically pure nitrogen heterocycles. The key to this process was the use of 2,2,2-trifluoroethyl diazoacetate as a superior nucleophilic reagent.
Angew. Chem. Int. Ed., Apr 29, 2013, DOI: 10.1002/anie.201301509
Renrong Liu, Junliang Zhang
Organocatalytic Michael Addition of Malonates to Isatylidene-3-acetaldehydes: Application to the Total Synthesis of (−)-Debromoflustramine E [Communication]
Flustering oxindoles: An enantioselective synthesis of 3,3'-disubstituted oxindoles by conjugate addition of malonates to isatylidene-3-acetaldehydes in high yield and enantioselectivity is developed (see scheme). The synthetic utility of this reaction is demonstrated by the synthesis of three oxindole core structures and the asymmetric total synthesis of debromoflustramine E.
You-Qing Wang, Yongna Zhang, Haina Dong, Jie Zhang, Jin Zhao
Phosphane-Catalyzed [3+2] Cycloaddition Reaction of Allenoate and Cyclic Imines: A Simple and Efficient Method for Synthesis of Benzo-Fused Cyclic Sulfamidate Heterocycles [Full Paper]
Olga Bortolini, Alberto Cavazzini, Pier Paolo Giovannini, Roberto Greco, Nicola Marchetti, Alessandro Massi, Luisa Pasti
A Combined Kinetic and Thermodynamic Approach for the Interpretation of Continuous-Flow Heterogeneous Catalytic Processes [Full Paper]
A good synergy: Reaction-progress kinetic analysis and nonlinear chromatography are useful tools for investigating a model aldol reaction performed in continuous-flow microreactors packed with proline-functionalized silica gel (see figure). The study was facilitated by a suitable instrumental arrangement for online monitoring; it also assessed optimal operating and feed variables.
Lei Wang, Jiayao Huang, Xiaojie Gong, Jian Wang
Highly Regioselective Organocatalyzed Synthesis of Pyrazoles from Diazoacetates and Carbonyl Compounds [Full Paper]
Dipoles apart: In situ formed enamines react with diazoacetates under mild conditions to afford the corresponding polysubstituted pyrazoles in good-to-excellent yields through an inverse-electron-demand 1,3-dipolar cycloaddition process (see scheme).
Jérémy Dardenne, Sandy Desrat, Françoise Guéritte, Fanny Roussi
Asymmetric Synthesis of Two Analogues of Meiogynin A [Full Paper]
Wei Yang, Ke-Zhi Jiang, Xing Lu, Hua-Meng Yang, Li Li, Yixin Lu, Li-Wen Xu
Molecular Assembly of an Achiral Phosphine and a Chiral Primary Amine: A Highly Efficient Supramolecular Catalyst for the Enantioselective Michael Reaction of Aldehydes with Maleimides [Full Paper]
Good, phosphine! An achiral phosphine is an ideal partner in the chiral-primary-amine-catalyzed enantioselective Michael reaction of aliphatic aldehydes with maleimides, thus enabling enantioselective induction in a dual organocatalytic system.
Chang An Wang, Yuan Zhang, Jiao Yi Shi, Wei Wang
A Self-Supported Polymeric MacMillan Catalyst for Homogeneous Organocatalysis and Heterogeneous Recycling [Communication]
Lean on me: A soluble, “self-supported” chiral organosilica polymer (ChiOSP) with embedded imidazolidinone catalytic moieties was synthesized by a bottom-up strategy and applied as a highly efficient and recyclable organocatalyst for the asymmetric Diels–Alder reaction.
Yuepeng Yan, Peng Feng, Qing-Zhong Zheng, Yu-Feng Liang, Jing-Fen Lu, Yuxin Cui, Ning Jiao
PdCl2 and N-Hydroxyphthalimide Co-catalyzed Csp2-H Hydroxylation by Dioxygen Activation [Communication]
Rad transition: The combination of transition-metal-catalyzed C-H activation and a NHPI-initiated radical process is essential for the title transformation. The neutral conditions and the ideal oxidant, molecular oxygen, make this hydroxylation environmentally friendly and practical. NHPI=N-hydroxyphthalimide.
Matthias Neumann, Kirsten Zeitler
A Cooperative Hydrogen-Bond-Promoted Organophotoredox Catalysis Strategy for Highly Diastereoselective, Reductive Enone Cyclization [Communication]
Metal-free cooperation: The cooperative combination of Eosin Y as a photoredox catalyst with organocatalytic thiourea allows for the highly diastereoselective construction of trans-1,2-cycloalkanes and heterocycles. This new efficient, cooperative organophotoredox/organocatalysis protocol presents a valuable alternative to metal-based photoredox approaches and is the first example of combining photoredox with hydrogen-bond catalysis (see scheme).
Li-Hui Sun, Zhi-Qin Liang, Wen-Qiang Jia, Song Ye
Enantioselective N-Heterocyclic Carbene Catalyzed Aza-Benzoin Reaction of Enals with Activated Ketimines [Communication]
α-Amino ketones, which are versatile building blocks for organic synthesis, were obtained with the title reaction. A free hydroxy group on the NHC catalyst was found to be crucial for the reaction, and the possible competing reaction through a homoenolate or enolate was not observed with this catalyst (see scheme).
Ibrayim Saidalimu, Xiang Fang, Xiao-Peng He, Jing Liang, Xueyan Yang, Fanhong Wu
Highly Enantioselective Construction of 3-Hydroxy Oxindoles through a Decarboxylative Aldol Addition of Trifluoromethyl α-Fluorinated gem-Diols to N-Benzyl Isatins [Communication]
An organocatalytic asymmetric direct aldol addition reaction that involves cleavage of a carbon–carbon bond through the release of trifluoroacetate was developed. The protocol is wide in scope, generating the desired oxindoles of biological interest in nearly quantitative yields (up to 99 %) with excellent enantioselectivities (up to 98 % ee) and diastereoselectivities (up to 99:1 d.r.).
Hiroyuki Kawai, Zhe Yuan, Takashi Kitayama, Etsuko Tokunaga, Norio Shibata
Efficient Access to Trifluoromethyl Diarylpyrrolines and their N-Oxides through Enantioselective Conjugate Addition of Nitromethane to β,β-Disubstituted Enones [Communication]
The cupreidinium salt 1 catalyzes the highly enantioselective conjugate addition of nitromethane to β-aryl-β-trifluoromethyl aryl enones (2). The biologically important chiral pyrrolines 4 and N-oxide 5, having a trifluoromethylated all-carbon quaternary chiral center, were easily synthesized from the key intermediate (R)-3 in high to excellent yields. M.S.=molecular sieves.
Taichi Kano, Taiga Yurino, Daisuke Asakawa, Keiji Maruoka
Acid-Catalyzed In Situ Generation of Less Accessible or Unprecedented N-Boc Imines from N-Boc Aminals [Communication]
Crafty aminals: The in situ generation of hitherto unattainable alkynyl-substituted N-Boc-protected imines was realized by the acid-catalyzed elimination of tert-butyl carbamate from N-Boc aminals. A wide variety of N-Boc imines can be generated, which can then be utilized for subsequent carbon–carbon bond-forming reactions, such as Mannich-type reactions.
Celia A. Incerti–Pradillos, Mikhail A. Kabeshov, Andrei V. Malkov
Highly Stereoselective Synthesis of Z-Homoallylic Alcohols by Kinetic Resolution of Racemic Secondary Allyl Boronates [Communication]
α to Z: Racemic α-chiral allyl boronates, which are readily synthesized from the respective primary allyl halides, undergo a highly efficient kinetic resolution in a face- and Z-selective allylation of aldehydes catalyzed by the chiral Brønsted acid (R)-TRIP (see scheme; Epin=tetraethylethylene glycol).
Xu Tian, Paolo Melchiorre
Control of Remote Stereochemistry in the Synthesis of Spirocyclic Oxindoles: Vinylogous Organocascade Catalysis [Communication]
Remote control: The title reaction facilitates the synthesis of complex chiral molecules while selectively forging multiple stereocenters at distant positions, namely five and six bond lengths away from the catalyst chiral fragment (see scheme; Boc=tert-butoxycarbonyl). The potential of the strategy is demonstrated through the one-step preparation of spirocyclopentane oxindoles having four contiguous stereocenters.
Hai-Lei Cui, Fujie Tanaka
Catalytic Enantioselective Formal Hetero-Diels–Alder Reactions of Enones with Isatins to Give Spirooxindole Tetrahydropyranones [Communication]
Organocatalytic formal hetero-Diels–Alder reactions of enones with isatins, which gave highly enantiomerically enriched functionalized spirooxindole tetrahydropyranones via an enamine-based mechanism, were developed. The catalyst systems were identified by a screen of combinations of amines, acids, and additives. With the identified catalyst systems, various spirooxindole tetrahydropyranones were synthesized in high yields with high diastereo- and enantioselectivities (see scheme).
Raman Tandon, Teresa Unzner, Tobias A. Nigst, Nicolas De Rycke, Peter Mayer, Bernd Wendt, Olivier R. P. David, Hendrik Zipse
Annelated Pyridines as Highly Nucleophilic and Lewis Basic Catalysts for Acylation Reactions [Full Paper]
A special relationship: Highly nucleophilic and Lewis basic derivatives of 9-azajulolidine have been synthesized and a good correlation between Lewis basicity and nucleophilicity has been obtained. The catalytic performance of these compounds in acylation reactions of sterically hindered alcohols is found to be more complex and quantitative prediction of reaction rates requires a three-component quantitative structure–activity relationship (QSAR) model including Lewis basicity, structural, and charge distribution parameters (see figure).
Juan Marco-Martínez, Vanesa Marcos, Silvia Reboredo, Salvatore Filippone, Nazario Martín
Asymmetric Organocatalysis in Fullerenes Chemistry: Enantioselective Phosphine-catalyzed Cycloaddition of Allenoates onto C60 [Communication]
Organocatalysis and fullerenes merge: The first asymmetric organocatalytic synthesis by phosphine-catalyzed [3+2] cycloaddition of allenoates onto [60]fullerene that occurs under mild conditions giving rise to enantiomerically pure carbocyclic fullerene derivatives is reported. X-ray analysis of a cyclopenteno[60]fullerene has allowed the assignment of the absolute configuration of the new stereocenter. Furthermore, the sector rule previously used to assign the chirality in [60]fullerenes has been corrected in the light of these new experimental findings.
Mei-Xin Zhao, Hao Zhou, Wen-Hao Tang, Wei-Song Qu, Min Shi
Cinchona Alkaloid-Derived Thiourea-Catalyzed Diastereo- and Enantioselective [3+2] Cycloaddition Reaction of Isocyanoacetates to Isatins: A Facile Access to Optically Active Spirooxindole Oxazolines [Communication]
Shu-rong Ban, Xi-xia Zhu, Zhi-ping Zhang, Hong-yu Xie, Qing-shan Li
Benzoylthiourea–Pyrrolidine as Another Bifunctional Organocatalyst: Highly Enantioselective Michael Addition of Cyclohexanone to Nitroolefins [Short Communication]
A benzoylthiourea–pyrrolidine catalyst was synthesized and used in the asymmetric Michael addition of ketones to nitroalkenes. The corresponding synthetically valuable γ-nitroketones were obtained in moderate to good yields with high levels of diastereo- and enantioselectivities (up to >99:1 dr and up to >99 % ee).
Yan ming Chen, Pei-Hsun Lee, Jun Lin, Kwunmin Chen
Desymmetrization and Switching of Stereoselectivity in Direct Organocatalytic Michael Addition of Ketones to 1,1-Bis(phenylsulfonyl)ethylene [Full Paper]
The direct organocatalytic desymmetrization was demonstrated for 4-substituted cyclohexanones by treatment with a vinyl sulfone in CHCl3. The desired Michael adducts were obtained in high chemical yields and stereoselectivities (up to 97 % yield, 93 % ee). Enantiomeric products were obtained by using either a camphor-derived pyrrolidine or a cinchonidine-derived primary amine as a catalyst.
Xin Li, Chen Yang, Jia-Lu Jin, Xiao-Song Xue, Jin-Pei Cheng
Synthesis of Optically Enriched Spirocyclic Benzofuran-2-ones by Bifunctional Thiourea-Base Catalyzed Double-Michael Addition of Benzofuran-2-ones to Dienones [Full Paper]
A double take: A highly enantioselective catalytic double-Michael addition reaction of substituted benzofuran-2-ones with divinyl ketones promoted by readily accessible tertiary amine–thiourea Cinchona alkaloids has been developed. A number of optically enriched spirocyclic benzofuran-2-ones were prepared in very good yields (up to 99 %), diastereoselectivities (up to 19:1 d.r.), and very good enantioselectivities (up to 92 % ee).
Wen-Yong Han, Shi-Wu Li, Zhi-Jun Wu, Xiao-Mei Zhang, Wei-Cheng Yuan
3-Isothiocyanato Oxindoles Serving as Powerful and Versatile Precursors to Structurally Diverse Dispirocyclic Thiopyrrolidineoxindoles through a Cascade Michael/Cyclization Process with Amino-Thiocarbamate Catalysts [Communication]
Cascading catalysis: 3-Isothiocyanato oxindoles act as powerful and versatile precursors for a range of structurally diverse dispirocyclic thiopyrrolidineoxindoles containing two spiro-quaternary and three contiguous stereogenic centers in quantitative yields with excellent disatereo- and enantioselectivities by only using 1 mol % amino-thiocarbamate catalyst.
Ai-Lan Lee
Organocatalyzed Carbonyl–Olefin Metathesis [Highlight]
The heat is on: A new [3+2] cycloaddition/cycloreversion strategy allows for catalytic and thermally allowed carbonyl–olefin metathesis (see scheme). This strategy opens opportunities for new developments in the field of carbonyl–olefin metathesis, which traditionally relied on stoichiometric amounts of transition-metal reagents or photochemical promotion.
Seiji Shirakawa, Keiji Maruoka
Recent Developments in Asymmetric Phase-Transfer Reactions [Review]
Work in process: The variations in the synthetic applications of phase-transfer reactions between 2006 and the middle of 2012 have been summarized to show the recent progress made in this field. The reactions have been applied to the synthesis of biologically active natural products and the large-scale preparation of drugs. The conceptually new catalyst design, reaction system, and reaction mode are also described.
Dieter Enders, Robert Hahn, Iuliana Atodiresei
Asymmetric Synthesis of Functionalized Tetrahydronaphthalenes via an Organocatalytic Nitroalkane-Michael/Henry Domino Reaction [Full Paper]
Hai-Xiao He, Wen Yang, Da-Ming Du
Enantioselective Aza-Henry Reaction of Imines Bearing a Benzothiazole Moiety Catalyzed by a Cinchona-Based Squaramide [Full Paper]
Junfeng Zhao, Christian Mück-Lichtenfeld, Armido Studer
Cooperative N-Heterocyclic Carbene (NHC) and Ruthenium Redox Catalysis: Oxidative Esterification of Aldehydes with Air as the Terminal Oxidant [Full Paper]
Steffen Fleischer, Shaolin Zhou, Svenja Werkmeister, Kathrin Junge, Matthias Beller
Cooperative Iron–Brønsted Acid Catalysis: Enantioselective Hydrogenation of Quinoxalines and 2 H-1,4-Benzoxazines [Communication]
Come together! A selective Fe-catalysed enantioselective reduction of quinoxalines and benzoxazines with hydrogen is demonstrated. Key to success is the combination of a chiral Brønsted acid and a well-defined non-chiral Fe hydrogenation catalyst. This methodology constitutes an attractive and environmentally favourable alternative to well-established asymmetric hydrogenations by using precious-metal-based catalysts.
Santhivardhana Reddy Yetra, Anup Bhunia, Atanu Patra, Manoj V. Mane, Kumar Vanka, Akkattu T. Biju
Enantioselective N-Heterocyclic Carbene-Catalyzed Annulations of 2-Bromoenals with 1,3-Dicarbonyl Compounds and Enamines via Chiral α,β-Unsaturated Acylazoliums [Full Paper]
Ji Hye Kim, Ilija Čorić, Sreekumar Vellalath, Benjamin List
The Catalytic Asymmetric Acetalization [Communication]
In straitened circumstances: In an asymmetric version of the acid-catalyzed acetalization of aldehydes, a novel member of the chiral confined Brønsted acid family significantly outperformed previously established catalysts, providing cyclic acetals with excellent enantioselectivity (see scheme; Ar=2-iPr-5-MeC6H3).
Liang Hong, Rui Wang
Recent Advances in Asymmetric Organocatalytic Construction of 3,3'-Spirocyclic Oxindoles [Review]
Suman De Sarkar, Anup Biswas, Ramesh C. Samanta, Armido Studer
Catalysis with N-Heterocyclic Carbenes under Oxidative Conditions [Concept]
Cascading down: Reaction of an aldehyde with an NHC provides the corresponding Breslow intermediate A, which can be readily oxidized with various organic and inorganic oxidants to give the acylazolium ion B (see scheme). Intermediate B can react with various nucleophiles either at the 2 or 4-position. With enals as starting aldehydes, elegant cascade processes have been developed using oxidative carbene catalysis.
Fabio Morana, Andrea Basso, Renata Riva, Valeria Rocca, Luca Banfi
The homo-PADAM Protocol: Stereoselective and Operationally Simple Synthesis of α-Oxo- or α-Hydroxy-γ-acylaminoamides and Chromanes [Full Paper]
A straightforward and fully stereoselective access to α-hydroxy-γ-acylaminoamides, α-oxo-γ-acylaminoamides, and chromanes is achieved by exploiting a sequence of: 1) an asymmetric organocatalytic Mannich reaction; 2) a Passerini multicomponent reaction; 3) an amine deprotection–acyl migration protocol; and 4) a final oxidation or cyclization. The whole sequence can be performed without purification of the intermediates.
Hai-Na Yuan, Shuai Wang, Jing Nie, Wei Meng, Qingwei Yao, Jun-An Ma
Hydrogen-Bond-Directed Enantioselective Decarboxylative Mannich Reaction of β-Ketoacids with Ketimines: Application to the Synthesis of Anti-HIV Drug DPC 083 [Communication]
Key to success: The title reaction provides facile access to enantioenriched 3,4-dihydroquinazolin-2(1H)-ones containing a quaternary stereogenic center in high yields with excellent enantioselectivities. Subsequent transformations lead to the convenient preparation of the anti-HIV drug DPC 083 and N-fused polycyclic compounds without loss of enantiomeric excess.
Jean-Marc M. Grandjean, David A. Nicewicz
Synthesis of Highly Substituted Tetrahydrofurans by Catalytic Polar-Radical-Crossover Cycloadditions of Alkenes and Alkenols [Communication]
Light up my ring: The title reaction is catalyzed by an acridinium/phenylmalononitrile photoredox system. A variety of readily available olefins and unsaturated alcohols can be employed to furnish tetrahydrofuran adducts with complete regiocontrol and up to four contiguous stereogenic centers.
Bor-Cherng Hong, Ding-Jyun Lan, Nitin S. Dange, Gene-Hsiang Lee, Ju-Hsiou Liao
Organocatalytic Enantioselective Michael–Henry Acetalization of Glutaraldehyde and 3-Aryl-2-nitroprop-2-enols: A Facile Entry to 3-Oxabicyclo[3.3.1]nonan-2-ones with Four Consecutive Stereogenic Centers [Full Paper]
![Organocatalytic Enantioselective Michael–Henry Acetalization of Glutaraldehyde and 3-Aryl-2-nitroprop-2-enols: A Facile Entry to 3-Oxabicyclo[3.3.1]nonan-2-ones with Four Consecutive Stereogenic Centers](http://www.wiley-vch.de/util/hottopics/img/ejoc201201496.jpg "Organocatalytic Enantioselective Michael–Henry Acetalization of Glutaraldehyde and 3-Aryl-2-nitroprop-2-enols: A Facile Entry to 3-Oxabicyclo[3.3.1]nonan-2-ones with Four Consecutive Stereogenic Centers")
A highly enantioselective Michael–Henry acetalization reaction of glutaraldehyde and 3-aryl-2-nitroprop-2-enols was achieved by the reaction with organocatalysts. Subsequent oxidation of the adducts provided the efficient synthesis of 3-oxabicyclo[3.3.1]nonan-2-ones with four consecutive stereogenic centers. X-ray analysis of the appropriate products confirmed the structures and absolute configurations of these adducts.
Eloah P. Avila, Amanda C. de Mello, Renata Diniz, Giovanni W. Amarante
Brønsted Acid Catalyzed Highly Diastereoselective Michael-Type Addition of Azlactones to Enones [Short Communication]
Arthur Michael and Johannes Nicolaus Brønsted as best friends: By combining different α,β-unsaturated enones and azlactones with a catalytic amount of (±)-camphorsulfonic acid (CSA), the corresponding Michael adducts were obtained with high diastereoselectivities.
Manuel Orlandi, Maurizio Benaglia, Laura Raimondi, Giuseppe Celentano
2-Aminoimidazolyl and 2-Aminopyridyl (S)-Prolinamides as Versatile Multifunctional Organic Catalysts for Aldol, Michael, and Diels–Alder Reactions [Full Paper]
The synthesis of multifunctional organocatalysts, easily obtained by the condensation of (S)-proline with 2-aminopyridine, 2,6-diaminopyridine, or 2-aminoimidazole is reported. These chiral prolinamides promoted the aldol condensation between cyclohexanone and different aromatic aldehydes (up to 98 % ee), and also catalysed Diels–Alder and Michael reactions.
Xufang Chang, Qiaohui Wang, Youming Wang, Haibin Song, Zhenghong Zhou, Chuchi Tang
Enantioselective Michael Addition of 4-Hydroxycoumarins to β,γ-Unsaturated α-Oxophosphonates Catalysed by a Bifunctional Squaramide Bearing a Structurally Rigid 9,10-Ethylene-9,10-dihydroanthracene Skeleton [Full Paper]
A one-pot synthesis of β-(4-hydroxy-2-oxo-2H-chromen-3-yl)-substituted carboxylates or amides has been developed by using a bifunctional-squaramide-catalysed asymmetric Michael addition of 4-hydroxycoumarins to β,γ-unsaturated α-oxophosphonates and the subsequent nucleophilic attack with alcohol or amine in the presence of DBU.
Dieu Nguyen, Ravish K. Akhani, Cody I. Sheppard, Sheryl L. Wiskur
Structure–Activity Relationship of Formamides as Organocatalysts: The Significance of Formamide Structure and Conformation [Short Communication]
A structure–activity relationship with regard to formamides as organocatalysts is explored. This study highlights that the cis conformation of secondary formamides is the reactive conformation in the allylation of aldehydes with allyltrichlorosilane. Therefore, conditions that promote an increase in the cis conformation result in greater amounts of product formed.
Ankita Rai, Lal Dhar S. Yadav
Cyclopropenone-Catalyzed Direct Conversion of Aldoximes and Primary Amides into Nitriles [Short Communication]
Cyclopropenone-catalyzed conversion of aldoximes and primary amides into nitriles in a one-pot procedure is described. The reaction proceeds smoothly under mild conditions with low catalyst loading. The convenient and catalytic procedure widens the scope of the utilization of cyclopropenones in organic synthesis.
Nico Erdmann, Arne R. Philipps, Iuliana Atodiresei, Dieter Enders
An Asymmetric Organocatalytic Quadruple Cascade Initiated by a Friedel–Crafts-Type Reaction with Electron-Rich Arenes [Communication]
Artur Noole, Maksim Ošeka, Tõnis Pehk, Mario Öeren, Ivar Järving, Mark R. J. Elsegood, Andrei V. Malkov, Margus Lopp, Tõnis Kanger
3-Chlorooxindoles: Versatile Starting Materials for Asymmetric Organocatalytic Synthesis of Spirooxindoles [Communication]
Jing Qi, Xingang Xie, Runfeng Han, Donghui Ma, Juan Yang, Xuegong She
N-Heterocyclic Carbene (NHC)-Catalyzed/Lewis Acid Mediated Conjugate Umpolung of Alkynyl Aldehydes for the Synthesis of Butenolides: A Formal [3+2] Annulation [Communication]
![N-Heterocyclic Carbene (NHC)-Catalyzed/Lewis Acid Mediated Conjugate Umpolung of Alkynyl Aldehydes for the Synthesis of Butenolides: A Formal [3+2] Annulation](http://www.wiley-vch.de/util/hottopics/img/chem201204386.gif "N-Heterocyclic Carbene (NHC)-Catalyzed/Lewis Acid Mediated Conjugate Umpolung of Alkynyl Aldehydes for the Synthesis of Butenolides: A Formal [3+2] Annulation")
Reverse to success! A new formal [3+2] annulation reaction combining alkynyl aldehydes and β,γ-unsaturated α-ketoesters has been disclosed by using a NHC-catalyzed/Lewis acid mediated strategy. This cooperative catalysis strategy first allows the “allenolate” intermediate as a nucleophilic synthon at the β-position to react with activated electrophilic reagents by an addition reaction as the key C-C bond-forming step.
Thibaut Courant, Sirirat Kumarn, Long He, Pascal Retailleau, Géraldine Masson
Chiral Phosphoric Acid-Catalyzed Enantioselective Aza-Friedel–Crafts Alkylation of Indoles with γ-Hydroxy-γ-lactams [Communication]
Aurélie Claraz, Sylvain Oudeyer, Vincent Levacher
Chiral Quaternary Ammonium Aryloxide/N,O-Bis(trimethyl- silyl)acetamide Combination as Efficient Organocatalytic System for the Direct Vinylogous Aldol Reaction of (5H)-Furan-2-one Derivatives [Communication]
Ilija Čorić, Ji Hye Kim, Tjøstil Vlaar, Mahendra Patil, Walter Thiel, Benjamin List
Brønsted Acid Catalyzed Asymmetric SN2-Type O-Alkylations [Communication]
Bridging the gap: Brønsted acids catalyze an intramolecular SN2-type alkylation of alcohols with ethers by bridging a pentacoordinate transition state, thus simultaneously activating both the leaving group and nucleophile (see scheme). Density functional calculations provide detailed insight into the course of the reaction and the transition-state structure.
Yujiro Hayashi, Shigenobu Umemiya
Pot Economy in the Synthesis of Prostaglandin A1 and E1 Methyl Esters [Communication]
Pot luck: Prostaglandins regulate a broad range of physiological processes and some of their derivatives are used as effective drugs, but previously their preparation has required many steps. The title compounds were efficiently synthesized in a small number of synthetic steps by using a recently developed organocatalyst and practical, one-pot operations involving several successive reactions.
Garazi Talavera, Efraím Reyes, Jose L. Vicario, Luisa Carrillo, Uxue Uria
Using Conveniently Designed α-Amino Ketones in Michael Reactions under Iminium Catalysis: Enantioselective Synthesis of γ-Lactams and γ-Amino-δ-keto Esters [Communication]
Jin-Xin Zhang, Nai-Kai Li, Zhao-Min Liu, Xiao-Fei Huang, Zhi-Cong Geng, Xing-Wang Wang
Enantioselective Synthesis of Unsymmetrical Diaryl-Substituted Spirocyclohexanonepyrazolones through a Cascade [4+2] Double Michael Addition [Update]
Xiaofei Zeng, Qijian Ni, Gerhard Raabe, Dieter Enders
A Branched Domino Reaction: Asymmetric Organocatalytic Two-Component Four-Step Synthesis of Polyfunctionalized Cyclohexene Derivatives [Communication]
Take two: By employing two equivalents of an aldehyde in an asymmetric organocatalytic domino reaction, the nucleophilic enamine intermediate is also converted into the corresponding iminium species through oxidation with o-iodoxybenzoic acid. Thus, polyfunctionalized cyclohexene derivatives are formed from two simple starting materials in good yields and stereoselectivities (see scheme; Bn=benzyl, EWG=electron-withdrawing group).
Hong-Wu Zhao, Hai-Long Li, Yuan-Yuan Yue, Zhui-Hui Sheng
Diastereoselective and Enantioselective Michael Addition Reactions of Ketones and Aldehydes to Nitro Olefins Catalyzed by C2-Symmetric Axially-Unfixed Biaryl-Based Organocatalysts Derived from Enantiopure α-Proline [Full Paper]
Facilitated by axially-unfixed biaryl-based bifunctional organocatalysts, the direct Michael addition reactions of ketones and aldehydes to nitro olefins gave Michael adducts in high chemical yields (up to 99 %) and with excellent stereoselectivities (up to 99:1 dr and 96 % ee).
Enric Mayans, Albert Gargallo, Angel Alvarez-Larena, Ona Illa, Rosa M. Ortuño
Diastereodivergent Synthesis of Chiral vic-Disubstituted-Cyclobutane Scaffolds: 1,3-Amino Alcohol and 1,3-Diamine Derivatives – Preliminary Use in Organocatalysis [Full Paper]
Chiral cyclobutane containing 1,3-amino alcohols and 1,3-diamines have been synthesized from a common chiral precursor. Regioselective transformations of these precursors led to bifunctional thioureas which have been tested as organocatalysts in preliminary experiments
Zhishan Su, Hai Whang Lee, Chan Kyung Kim
Asymmetric 1,4-Michael Addition Reactions Catalyzed by a Cinchona Alkaloid Derived Primary Amine: A Theoretical Investigation of the Reaction Mechanism and Enantioselectivity [Full Paper]
Asymmetric 1,4-Michael addition catalyzed by a cinchona alkaloid proceeds by a dual activation mechanism involving a primary amine and quinuclidine moiety interacting simultaneously with electrophiles and nucleophiles through iminium catalysis. Steric interactions force the ketiminium ion intermediate to adopt a conformation more accessible to Re-face attack.
Hailong Zhang, Xiaozhou Ma, Hong Kang, Liang Hong, Rui Wang
The Enantioselective Formal Synthesis of Rhynchophylline and Isorhynchophylline [Communication]
Formal attire: An enantioselective formal total synthesis of the alkaloids isorhynchophylline and rhynchophylline is described. The key steps include an organocatalyzed asymmetric Michael addition reaction and an efficient diastereoselective intramolecular iminium ion spirocyclization/lactamization cascade sequence.
Jannie Christensen, Łukasz Albrecht, Karl Anker Jørgensen
Stereocontrolled Organocatalytic Strategy for the Synthesis of Optically Active 2,3-Disubstituted cis-2,3-Dihydrobenzofurans [Full Paper]
An intramolecular, organocatalyzed Michael addition to obtain biologically important 2,3-disubstituted cis-2,3-dihydrobenzofurans has been developed. By using mandelic acid salts of primary aminocatalysts, derived from cinchona alkaloids, the intramolecular cyclization reaction proceeded in high yield, with moderate to good diastereoselectivity, and up to 99 % ee.
Long Chen, Tao-Da Shi, Jian Zhou
Waste as Catalyst: Tandem Wittig/Conjugate Reduction Sequence to α-CF3 γ-Keto Esters That Uses Ph3PO as Catalyst for the Chemoselective Conjugate Reduction [Communication]
Reduce your waist: A highly efficient synthesis of α-CF3 γ-keto esters and trifluoromethylated 4,5-dihydro pyridazinones is reported based on tandem Wittig–conjugate reduction reactions, which directly utilize the Ph3PO waste from the Wittig reaction as the Lewis base catalyst to activate HSiCl3 for the chemoselective conjugate reduction.
Christina Moberg
Mechanism of Diphenylprolinol Silyl Ether Catalyzed Michael Addition Revisited—but Still Controversial [Highlight]
Two views: The mechanism of the conjugate addition of linear aldehydes to nitro olefins has been investigated by two research groups. In spite of extensive experimental data, important questions remain unanswered (see scheme; TMS=trimethylsilyl, En=enamine).
Pankaj Chauhan, Jasneet Kaur, Swapandeep Singh Chimni
Asymmetric Organocatalytic Addition Reactions of Maleimides: A Promising Approach Towards the Synthesis of Chiral Succinimide Derivatives [Focus Review]
Taking the Michael: Recent progress in asymmetric organocatalysis has led to the development of several asymmetric transformations that employ various substrates. Among these substrates, maleimides have emerged as excellent Michael acceptors, dienophiles, and dipolarophiles. In this Focus Review we highlight the advances in the asymmetric synthesis of succinimide derivatives.
Ommidala Pattawong, Thomas J. L. Mustard, Ryne C. Johnston, Paul Ha-Yeon Cheong
Mechanism and Stereocontrol: Enantioselective Addition of Pyrrole to Ketenes Using Planar-Chiral Organocatalysts [Communication]
In control: The computational study of the title reaction catalyzed by the planar-chiral 4-(pyrrolidino)pyridine is reported (see scheme). The resting state is a chiral Brønsted acid complex and the rate-determining step involves a chiral base. The catalyst controls the enantioselectivity through a combination of stereoelectronic effects and CH···O interactions.
Jitka Dadová, Susanne Kümmel, Christian Feldmeier, Jana Cibulková, Richard Pažout, Jaroslav Maixner, Ruth M. Gschwind, Burkhard König, Radek Cibulka
Aggregation Effects in Visible-Light Flavin Photocatalysts: Synthesis, Structure, and Catalytic Activity of 10-Arylflavins [Full Paper]
Shining light on increased activity: Aryl rings that are perpendicularly oriented relative to the flavin chromophore substantially decrease aggregation relative to nonsubstituted derivatives. These 10-arylflavin derivatives are more efficient photocatalysts for the oxidation of 4-methoxybenzyl alcohol (see scheme).
Manuel Mahlau, Benjamin List
Asymmetric Counteranion-Directed Catalysis: Concept, Definition, and Applications [Review]
Opposites attract: This simple realization is the basis for asymmetric counteranion-directed catalysis (ACDC). All reactions proceeding via cationic intermediates are accompanied by a counteranion. Inducing high enantioselectivities in these reactions merely by ion pairing with an enantiomerically pure counteranion has been achieved for the first time during recent years.
Albrecht Berkessel, Jan Krämer, Florian Mummy, Jörg-M. Neudörfl, Rainer Haag
Dendritic Fluoroalcohols as Catalysts for Alkene Epoxidation with Hydrogen Peroxide [Communication]
Cooperativity is the key for mild catalytic epoxidation: The immobilization of fluoroalcohols on dendritic polyglycerol (by “click chemistry”) provides organocatalysts that can form multiple hydrogen bonds. The epoxidation of alkenes with aqueous hydrogen peroxide proceeds efficiently in the presence of dendritic fluoroalcohol catalysts. The supported catalysts can be separated by membrane filtration and reused.
Shaozhen Wang, Long Kuai, Yucheng Huang, Xue Yu, Yadong Liu, Wenzheng Li, Lu Chen, Baoyou Geng
A Highly Efficient, Clean-Surface, Porous Platinum Electrocatalyst and the Inhibition Effect of Surfactants on Catalytic Activity [Full Paper]
Catalyst inhibition: Clean-surface, porous, platinum nanoparticles were obtained by a surfactant-free method. Compared with a Pt/C catalyst, the porous nanostructures exhibit higher mass and specific activities. The inhibition effects of various surfactants was investigated electrochemically, and a surface-group-induced selective inhibition was discovered (see figure; CTAB=cetyltrimethylammonium bromide, SDS=sodium dodecyl sulfate, PVP=poly(vinylpyrrolidone)).
Łukasz Albrecht, Gustav Dickmeiss, Christian F. Weise, Carles Rodríguez-Escrich, Karl Anker Jørgensen
Dienamine-Mediated Inverse-Electron-Demand Hetero-Diels–Alder Reaction by Using an Enantioselective H-Bond-Directing Strategy [Communication]
Giving directions: Optically active dihydropyrans bearing three contiguous stereogenic centers can be efficiently prepared by the title reaction. High stereo- and regiocontrol can be achieved by employing a bifunctional H-bond-directing aminocatalyst.
Boyu Zhang, Zongxuan Jiang, Xin Zhou, Shengmei Lu, Jun Li, Yan Liu, Can Li
The Synthesis of Chiral Isotetronic Acids with Amphiphilic Imidazole/Pyrrolidine Catalysts Assembled in Oil-in-Water Emulsion Droplets [Communication]
Drop it! A highly enantioselective catalytic cascade reaction of α-ketoacids and aldehydes is achieved using the title catalyst and water as the solvent. Fluorescence imaging shows that the catalyst is mainly distributed on the surface of emulsion droplets. Optically active isotetronic acids can be obtained with this method and the emulsion droplets are responsible for the high reactivity and enantioselectivity.
Chun-Xiang Zhuo, Wei Zhang, Shu-Li You
Catalytic Asymmetric Dearomatization Reactions [Review]
Breaking up the party: Arenes can be transformed efficiently into enantiomerically enriched, versatile ring systems by catalytic asymmetric dearomatization reactions. Known reaction types include oxidative dearomatization, dearomatization by Diels—Alder reactions, alkylative dearomatization of electron-rich arenes, transition-metal-catalyzed dearomatization reactions (see example), and cascade reaction sequences involving asymmetric dearomatization as the key step.
Keisuke Yoshida, Kenji Mishiro, Yoshihiro Ueda, Takashi Shigeta, Takumi Furuta, Takeo Kawabata
Non-Enzymatic Geometry-Selective Acylation of Tri- and Tetrasubstituted α,α'-Alkenediols [Full Paper]
Tadashi Ema, Kumiko Akihara, Ryoko Obayashi, Takashi Sakai
Construction of Contiguous Tetrasubstituted Carbon Stereocenters by Intramolecular Crossed Benzoin Reactions Catalyzed by N-Heterocyclic Carbene (NHC) Organocatalyst [Full Paper]
J. Stephen Clark, Alistair Boyer, Anthony Aimon, Paloma Engel García, David M. Lindsay, Andrew D. F. Symington, Yves Danoy
Organocatalytic Synthesis of Highly Substituted Furfuryl Alcohols and Amines [Communication]
Top cat! Tetrahydrothiophene is an efficient organocatalyst for the synthesis of highly substituted furfuryl products from readily accessible electron-poor enynes under neutral reaction conditions. This process is applicable to a wide range of nucleophiles and enynes and can be used in a domino organocatalysis sequence.
Feng Shi, Liu-Zhu Gong
Relay Catalysis Enables Hydrogen Gas to Participate in Asymmetric Organocatalytic Hydrogenation [Highlight]
Teamwork: Through relay catalysis by a RuII complex and a chiral phosphoric acid ((S)-BPA in the scheme) recently developed by Zhou's group, hydrogen gas can act as the terminal reductant in the catalytic asymmetric hydrogenation of heterocycles. This is a completely new concept in the area of asymmetric hydrogenation.
Olga V. Serdyuk, Alexandru Zamfir, Frank Hampel, Svetlana B. Tsogoeva
Combining in situ Generated Chiral Silicon Lewis Acid and Chiral Brønsted Acid Catalysts for [3+2] Cycloadditions: Cooperative Catalysis as a Convenient Enantioselective Route to Pyrazolidines [Update]
María D. Díaz-de-Villegas, José A. Gálvez, Ramón Badorrey, M. Pilar López-Ram-de-Víu
Organocatalyzed Enantioselective Desymmetrization of Diols in the Preparation of Chiral Building Blocks [Minireview]
Breaking symmetry: Discrimination between enantiotopic hydroxyl groups in prochiral and meso-diols is a powerful methodology for the preparation of important chiral building blocks (see scheme). Organocatalysis offers a valuable alternative to the classical methods used in this transformation, which is beginning to provide promising results in cheaper and cleaner processes.
Guangning Ma, Shuangzheng Lin, Ismail Ibrahem, Grzegorz Kubik, Leifeng Liu, Junliang Sun, Armando Córdova
Achiral Co-Catalyst Induced Switches in Catalytic Asymmetric Reactions on Racemic Mixtures (RRM): From Stereodivergent RRM to Stereoconvergent Deracemization by Combination of Hydrogen Bond Donating and Chiral Amine Catalysts [Update]
Yingpeng Su, Marinus J. Bouma, Lilian Alcaraz, Mike Stocks, Mark Furber, Géraldine Masson, Jieping Zhu
Organocatalytic Enantioselective One-Pot Four-Component Ugi-Type Multicomponent Reaction for the Synthesis of Epoxy-tetrahydropyrrolo[3,4-b]pyridin-5-ones [Communication]
![Organocatalytic Enantioselective One-Pot Four-Component Ugi-Type Multicomponent Reaction for the Synthesis of Epoxy-tetrahydropyrrolo[3,4-b]pyridin-5-ones](http://www.wiley-vch.de/util/hottopics/img/chem201202174.gif "Organocatalytic Enantioselective One-Pot Four-Component Ugi-Type Multicomponent Reaction for the Synthesis of Epoxy-tetrahydropyrrolo[3,4-b]pyridin-5-ones")
Enantioselective multicomponent reaction: In the presence of a catalytic amount of chiral BINOL-derived phosphoric acid (TRIP), the reaction of an α-isocyanoacetate 1, an aldehyde 2, and an aniline 3, followed by addition of a toluene solution of α,β-unsaturated acyl chloride 4 afforded the oxa-bridged tricycle 5 in excellent yield, diastereoselectivity, and enantioselectivity. Six chemical bonds, five stereogenic centers, and three cycles were formed in this one-pot four-component reaction.
Paolo Melchiorre
Cinchona-based Primary Amine Catalysis in the Asymmetric Functionalization of Carbonyl Compounds [Review]
Primary choice: In only five years, cinchona-based primary amine catalysis has almost equaled the high level of efficiency and reliability of aminocatalysis by proline-derived catalysts, offering the unique possibility of effecting reactions between sterically demanding carbonyl compounds (see picture).
Alejandro Parra, Silvia Reboredo, José Alemán
Asymmetric Synthesis of Cyclobutanes by a Formal [2+2] Cycloaddition Controlled by Dienamine Catalysis [Highlight]
![Asymmetric Synthesis of Cyclobutanes by a Formal [2+2] Cycloaddition Controlled by Dienamine Catalysis](http://www.wiley-vch.de/util/hottopics/img/anie201203489.gif "Asymmetric Synthesis of Cyclobutanes by a Formal [2+2] Cycloaddition Controlled by Dienamine Catalysis")
Trap it: A combination of aminocatalysis with H-bonding activation is used in two new approaches to carry out formal enantioselective organocatalyzed [2+2] cycloaddition reactions. This cooperative catalysis solves the inconveniences associated with this transformation. These two new reactions will open opportunities to find reactivities involving other organocatalytic cycloadditions.
Michael Wilsdorf, Hans-Ulrich Reissig
Simple, but Challenging: Recent Developments in the Asymmetric Synthesis of Spiroketals [Highlight]
Impressive and elegant approaches to the enantioselective synthesis of spiroketals starting from achiral substrates have been described recently. These strategies based on transition-metal catalysis and organocatalysis hold great potential for further applications.
Eugenia Marqués-López, Mathias Christmann
β-Lactones through Catalytic Asymmetric Heterodimerization of Ketenes [Highlight]
Simple, but effective: The asymmetric heterodimerization of two different ketenes (see scheme) has been developed 65 years after the first seminal studies on ketene dimerization. The key to sufficiently suppressing the competing homodimerization of the monosubstituted ketene donor (shown in blue) is its slow addition to the disubstituted acceptor (shown in red).
Ulrich Lüning
Switchable Catalysis [Highlight]
On/off catalysts: Control over catalysis can be gained when the catalysts can be switched between an active and a nonactive state by external stimuli. In recent examples, orthogonal signals—light, pH, or the addition of ions—are used for the switching.
Charles C. J. Loh, Dieter Enders
Merging Organocatalysis and Gold Catalysis—A Critical Evaluation of the Underlying Concepts [Minireview]
A ‘golden’ handshake: While organocatalysis and gold catalysis have evolved as pivotal areas in modern organic synthesis, a novel niche area, namely, the merger of both catalytic systems in the same reaction flask, has not been put under the spotlight until the last four years. Moreover, the synthetic utility of this young emerging concept has permeated major areas of organocatalysis, and therefore, a systematic Minireview of this rapidly growing area is presented.
Romain Blanc, Paola Nava, Michel Rajzman, Laurent Commeiras, Jean-Luc Parrain
N-Heterocyclic Carbene-Mediated Organocatalytic Transfer of Tin onto Aldehydes: An Easy Access to syn-Diols and Mechanistic Studies [Update]
Harit U. Vora, Philip Wheeler, Tomislav Rovis
Exploiting Acyl and Enol Azolium Intermediates via N-Hetero- cyclic Carbene-Catalyzed Reactions of α-Reducible Aldehydes [Review]
Cheng-Kui Pei, Min Shi
Asymmetric Cyclization Reactions of Allenoates with Imines or α,β-Unsaturated Ketones Catalyzed by Organocatalysts Derived from Cinchona Alkaloids [Concept]
Asymmetric organocatalysis: Lewis base-catalyzed cyclization reactions of allenoates with electron-deficient olefins and imines have been applied in the preparation of biologically active natural products and pharmaceutically interesting substances and have emerged as powerful synthetic tools in the rapid construction of cyclic molecular complexity. In contrast to phosphine-containing Lewis bases, nitrogen-containing Lewis base amines display markedly different reaction profiles; however, this area is not well-developed.
Dipti S. Kundu, Johannes Schmidt, Christian Bleschke, Arne Thomas, Siegfried Blechert
A Microporous Binol-Derived Phosphoric Acid [Communication]
No slow down: A microporous recyclable heterogeneous catalyst made from a 1,1'-binaphthalene-2,2'-diol (binol)-derived phosphoric acid chloride is as active as the corresponding homogeneous catalyst when using the same mass of both in different reactions. Reaction rates, yields, and enantioselectivities are comparable.
Shinobu Takizawa, Tue Minh-Nhat Nguyen, André Grossmann, Dieter Enders, Hiroaki Sasai
Enantioselective Synthesis of α-Alkylidene-γ-Butyrolactones: Intramolecular Rauhut–Currier Reaction Promoted by Acid/Base Organocatalysts [Communication]
Teaming up: The title reaction has been developed to deliver the product α-alkylidene-γ-butyrolactones as single diastereomers with up to 98 % ee (see scheme; Ts=4-toluenesulfonyl). The enantioselective process is catalyzed by 1, which contains both Lewis base and Brønsted acid moieties.
Elena Arceo, Paolo Melchiorre
Extending the Aminocatalytic HOMO-Raising Activation Strategy: Where Is the Limit? [Highlight]
Increasingly remote stereocenters are being targeted in asymmetric aminocatalysis. Application of the HOMO-raising activation concept to δ,δ-disubstituted 2,4-dienones confirms the powerful potential of the trienamine strategy. A cinchona-based primary amine catalyst enables the extension of this activation mode to a highly selective asymmetric Diels–Alder reaction of enones with electron-deficient dienophiles (see scheme; TFA: trifluoroacetic acid).
Bin Tan, Gloria Hernández-Torres, Carlos F. Barbas, III
Rationally Designed Amide Donors for Organocatalytic Asymmetric Michael Reactions [Communication]
Amide nucleophiles on demand: Rationally designed pyrazoleamides function as Michael donors in urea-catalyzed asymmetric Michael reactions with excellent chemical and optical yields (see scheme). The pyrazoleamide group performs as an ester equivalent, a directing group, an activating group, and functions as a good leaving group in further transformations of the product.
Maria Cherevatskaya, Matthias Neumann, Stefan Füldner, Christoph Harlander, Susanne Kümmel, Stephan Dankesreiter, Arno Pfitzner, Kirsten Zeitler, Burkhard König
Visible-Light-Promoted Stereoselective Alkylation by Combining Heterogeneous Photocatalysis with Organocatalysis [Communication]
Dream team: Heterogeneous inorganic semiconductors and chiral organocatalysts team up for the stereoselective photocatalytic formation of carbon–carbon bonds. However, the connection between the organic and inorganic catalysts should not be too tight: Covalent immobilization inactivates the system.
Wen-Quan Zhang, Ling-Feng Cheng, Jie Yu, Liu-Zhu Gong
A Chiral Bis(betaine) Catalyst for the Mannich Reaction of Azlactones and Aliphatic Imines [Communication]
By design: New chiral bis(betaine)s, for example 1, containing two catalytically active centers have been designed. They have proven to be promising organocatalysts for the direct Mannich-type reaction of azlactones with a broad spectrum of aliphatic imines, thus affording α-tetrasubstituted α,β-diamino acid surrogates with excellent enantioselectivities.
Garazi Talavera, Efraím Reyes, Jose L. Vicario, Luisa Carrillo
Cooperative Dienamine/Hydrogen-Bonding Catalysis: Enantioselective Formal [2+2] Cycloaddition of Enals with Nitroalkenes [Communication]
![Cooperative Dienamine/Hydrogen-Bonding Catalysis: Enantioselective Formal [2+2] Cycloaddition of Enals with Nitroalkenes](http://www.wiley-vch.de/util/hottopics/img/anie201200269.gif "Cooperative Dienamine/Hydrogen-Bonding Catalysis: Enantioselective Formal [2+2] Cycloaddition of Enals with Nitroalkenes")
Two can play this game: The title reaction is catalyzed by a chiral secondary amine in the presence of an achiral thiourea for the enantio- and diastereoselective synthesis of highly functionalized cyclobutanes (see scheme; TMS=trimethylsilyl). Mechanistically, two consecutive Michael reactions proceed through an unprecedented combination of an dienamine/iminium activation mode.
Ulrich Hennecke
New Catalytic Approaches towards the Enantioselective Halogenation of Alkenes [Focus Review]
Technical difficulties: Enantioselective, electrophilic halogen additions to alkenes have often been described as difficult reactions. Recently, this problem has been addressed with many novel catalytic methods. In this focus review these methods will be summarized highlighting common themes and mechanistic considerations.
Alberto Fraile, Daniele M. Scarpino Schietroma, Anna Albrecht, Rebecca L. Davis, Karl Anker Jørgensen
Asymmetric Synthesis of Hexahydropyrrolo-isoquinolines by an Organocatalytic Three-Component Reaction [Communication]
Merging three in one by a three-component organocatalytic asymmetric reaction of imines and α-bromoesters or ketones with α,β-unsaturated aldehydes provides optically active pyrrolo-isoquinolines—an important class of molecules in life science. The reaction proceeds with excellent enantioselectivity and a number of transformations of the products obtained demonstrated the potential of the new reaction.
Michail Tsakos, Christoforos G. Kokotos, George Kokotos
Primary Amine-Thioureas with Improved Catalytic Properties for “Difficult” Michael Reactions: Efficient Organocatalytic Syntheses of (S)-Baclofen, (R)-Baclofen and (S)-Phenibut [Update]
Hélène Pellissier
Recent Developments in Asymmetric Organocatalytic Domino Reactions [Review]
Dhevalapally B. Ramachary, Y. Vijayendar Reddy
Dienamine Catalysis: An Emerging Technology in Organic Synthesis [Microreview]
This microreview describes the reaction engineering of dienamine catalysis for single-step syntheses of highly functionalized molecules such as natural products orbioactive compounds. Here we discuss the entire saga of dienamine chemistry from “preformed dienamines” to “in situ dienamines” and its evolution as unique technology in organic synthesis.
André Grossmann, Dieter Enders
N-Heterocyclic Carbene Catalyzed Domino Reactions [Minireview]
Every Jack will find his Jill: Uniting unique activation modes of N-heterocyclic carbene (NHC) catalysts with the concept of domino reactions (see picture, EWG=electron-withdrawing group), a new fast-growing field came into the spotlight in last three years. The state of the art of this field is presented and the definition of the domino reactions for the NHC catalysis is re-considered.
Wilfried Raimondi, Damien Bonne, Jean Rodriguez
1,2-Dicarbonyl Compounds as Pronucleophiles in Organocatalytic Asymmetric Transformations [Highlight]
Organocatalysis likes them too! 1,2-dicarbonyl compounds possess high synthetic potential because of their adjacent multiple reactive centers. Recent contributions indicate that these reactive species, with an appropriate activation mode, may also act as efficient pronucleophiles in asymmetric organocatalyzed sequential or domino transformations including C-C or C-N bond formation (see scheme).
Charles C. J. Loh, Dieter Enders
Exploiting the Electrophilic Properties of Indole Intermediates: New Options in Designing Asymmetric Reactions [Highlight]
Think electrophilic: While the classical π-excessive indole is well-known for its electrophilic substitutions at position C3, recent advances in asymmetric catalysis resulted in a surge in utilizing the less discussed electrophilic properties of iminium-type intermediates (see picture) in complex annulations of indoles. Advances in AuI catalysis also allow an umpolung of the classical indole C3 reactivity.
Joe P. Richmond
New Developments in Advanced Synthesis & Catalysis: Growth and High-Impact Research for Green Organic Synthesis [Commentary]
© Wiley-VCH 2011.
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