Hot TopicsWiley-VCH

ASCEurJOCChem Eur JAngewandte

Organocatalysis

ACh cover 24/2003The 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]

[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.

Recent Articles

RSS feed

Stéphane Lebrun, Romain Sallio, Mélanie Dubois, Francine Agbossou-Niedercorn, Eric Deniau, Christophe Michon
Chiral Phase-Transfer-Catalyzed Intramolecular aza-Michael Reactions for the Asymmetric Synthesis of Isoindolinones [Full Paper]

Chiral Phase-Transfer-Catalyzed Intramolecular aza-Michael Reactions for the Asymmetric Synthesis of Isoindolinones

Asymmetric intramolecular aza-Michael reactions with cinchoninium phase-transfer organocatalysts are used for the synthesis of optically active isoindolinones. The resulting compounds are useful intermediates for the synthesis and development of benzodiazepine-receptor agonists.

Eur. J. Org. Chem., February 5, 2015, DOI: 10.1002/ejoc.201403573

Direct Organocatalytic Oxo-Metathesis, a trans-Selective Carbocation-Catalyzed Olefination of Aldehydes

A new partner in the metathesis dance: Trityl tetrafluoroborate (TrBF4) catalyzes the direct oxo-metathesis of aldehydes and unactivated olefins to give β-alkylstyrene derivatives and acetone through an unusual metal-free formal [2+2]/retro [2+2] reaction sequence.

Eur. J. Org. Chem., February 5, 2015, DOI: 10.1002/ejoc.201403651

Michal Majek, Fabiana Filace, Axel Jacobi von Wangelin
Visible Light Driven Hydro-/Deuterodefunctionalization of Anilines [Communication]

Visible Light Driven Hydro-/Deuterodefunctionalization of Anilines

Light it up! Synthetic and mechanistic aspects of a novel protocol for the defunctionalization of aniline derivatives are presented. Arenediazonium salts undergo facile reductive defunctionalization in the presence of eosin B as cheap organic catalyst under visible light. DMF and deuterated DMF serve as stoichiometric hydride and deuteride donors to give benzenes and deuterobenzenes, respectively (see scheme). Both photoredox catalysis and radical chain propagation mechanisms are operating.

Chem. Eur. J., Feb 05, 2015, DOI: 10.1002/chem.201406461

Yongqiang Zhang, Shanchao Wu, Shengzheng Wang, Kun Fang, Guoqiang Dong, Na Liu, Zhenyuan Miao, Jianzhong Yao, Jian Li, Wannian Zhang, Chunquan Sheng, Wei Wang
Divergent Cascade Construction of Skeletally Diverse “Privileged” Pyrazole-Derived Molecular Architectures [Full Paper]

Divergent Cascade Construction of Skeletally Diverse “Privileged” Pyrazole-Derived Molecular Architectures

A powerful divergent cascade strategy has been developed for the rapid construction of five distinct diverse enantioenriched pyrazole-derived scaffolds using only six simple building blocks. Furthermore, screening of 10 compounds exemplifying the five synthesized scaffolds revealed potent anticancer lead compounds.

Eur. J. Org. Chem., February 5, 2015, DOI: 10.1002/ejoc.201403673

Christian Beceño, Pankaj Chauhan, Andreas Rembiak, Ai Wang, Dieter Enders
Brønsted Acid-Catalyzed Enantioselective Synthesis of Isatin- Derived N,S-Acetals [Communication]

Constanze N. Neumann, Tobias Ritter
Late-Stage Fluorination: Fancy Novelty or Useful Tool? [Essay]

Late-Stage Fluorination: Fancy Novelty or Useful Tool?

Charming fluorine: This Essay examines the recent surge in late-stage fluorination reactions and outlines challenges that need to be overcome to increase the impact of modern fluorination methods on the synthesis of complex organofluorine compounds. It is outlined how an improved understanding of the bonding interactions of fluoride could lead to a new class of mild fluorinating reagents and a range of functional-group-tolerant reactions.

Angew. Chem. Int. Ed., February 4, 2015, DOI: 10.1002/anie.201410288

Mikk Kaasik, Artur Noole, Kärt Reitel, Ivar Järving, Tõnis Kanger
Organocatalytic Conjugate Addition of Cyclopropylacetaldehyde Derivatives to Nitro Olefins: en Route to β- and γ-Amino Acids [Full Paper]

Organocatalytic Conjugate Addition of Cyclopropylacetaldehyde Derivatives to Nitro Olefins: en Route to β- and γ-Amino Acids

Cyclopropane-containing amino acids can be synthesised through an organocatalytic asymmetric Michael reaction. The cyclopropane ring, as well as two different nitrogen-containing functional groups (tert-butoxycarbonylamino and nitro) are introduced in one step. The products were isolated in good yields with moderate to excellent enantio- and diastereoselectivities.

Eur. J. Org. Chem., January 29, 2015, DOI: 10.1002/ejoc.201403387

Olivier Mahé, Jean-François Brière, Isabelle Dez
Chitosan: An Upgraded Polysaccharide Waste for Organocatalysis [Microreview]

Chitosan: An Upgraded Polysaccharide Waste for Organocatalysis

This microreview outlines recent advances in achiral to asymmetric organocatalytic reactions based on chitosan, a biodegradable chiral polysaccharide obtained from marine wastes, in a sustainable chemistry context. The use of chitosan and its derivatives either as insoluble organocatalysts or as supports for organocatalysts is reviewed, together with shaping and reusability issues.

Eur. J. Org. Chem., January 29, 2015, DOI: 10.1002/ejoc.201403396

An Organocatalytic Mannich/Denitration Reaction for the Asymmetric Synthesis of 3-Ethylacetate-Substitued 3-Amino-2-Oxindoles: Formal Synthesis of AG-041R

Traceless stereocontrol: The nucleophilic addition of ethyl nitroacetate to isatin-derived ketimines, followed by the removal of the nitro group, opens an efficient route to oxindole key intermediates of pyrroloindoline alkaloids and related pharmaceuticals of high enantiomeric purity. The Mannich or aza-Henry-type reaction is catalyzed by a dihydroquinine-based Brønsted base (see scheme). The easily scalable protocol is demonstrated by a formal synthesis of the bioactive lead compound AG-041R.

Chem. Eur. J., January 28, 2015, DOI: 10.1002/chem.201406422

Antonio De Nino, Loredana Maiuolo, Pedro Merino, Monica Nardi, Antonio Procopio, David Roca-López, Beatrice Russo, Vincenzo Algieri
Efficient Organocatalyst Supported on a Simple Ionic Liquid as a Recoverable System for the Asymmetric Diels–Alder Reaction in the Presence of Water [Full Paper]

Efficient Organocatalyst Supported on a Simple Ionic Liquid as a Recoverable System for the Asymmetric Diels–Alder Reaction in the Presence of Water

Confirming the conformation: The synthesis, characterization, and evaluation of a new highly efficient imidazolidinone organocatalyst is achieved. The catalyst is investigated in enantioselective Diels–Alder reactions, and a conformation study confirms the approach on the less hindered Si face. [mPy][OTf]=Methylpyridinium triflate.

ChemCatChem, January 28, 2015, DOI: 10.1002/cctc.201402973

Amino-Acid Derived Phosphine-Catalyzed Enantioselective 1,4-Dipolar Spiroannulation of Cyclobutenones and Isatylidenemalononitrile

Cyclobutenones are explored as a new type of chiral 1,4-dipole four-carbon synthon, which readily undergoes asymmetric intermolecular 1,4-dipolar spiroannulation with isatylidenemalononitrile in the presence of amino-acid derived chiral phosphine catalyst to furnish enantioenriched 3-spirocyclohexenone 2-oxindoles in good yield with up to 87 % ee.

Chem. Eur. J., January 28, 2015, DOI: 10.1002/chem.201406475

Christopher T. Check, Ki Po Jang, C. Benjamin Schwamb, Alexander S. Wong, Michael H. Wang, Karl A. Scheidt
Ferrocene-Based Planar Chiral Imidazopyridinium Salts for Catalysis [Communication]

Ferrocene-Based Planar Chiral Imidazopyridinium Salts for Catalysis

Planar chiral azolium salts that incorporate a sterically demanding iron sandwich complex are synthesized. These new N-heterocyclic carbenes can be employed both as organocatalysts and as ligands for transition-metal catalysis, which demonstrates their unprecedented versatility and potential broad utility in asymmetric catalysis.

Angew. Chem. Int. Ed., January 23, 2015, DOI: 10.1002/anie.201410118

Elisa Huerta , Bas van Genabeek , Brigitte A. G. Lamers, Marcel M. E. Koenigs, E. W. Meijer, Anja R. A. Palmans
Triggering Activity of Catalytic Rod-Like Supramolecular Polymers [Full Paper]

Triggering Activity of Catalytic Rod-Like Supramolecular Polymers

Self-assembled organocatalysts: A temperature-triggered conformational change in supramolecular polymers with pendant L-proline units results in highly active and selective organocatalysts for aldol reactions in water (see scheme).

Chem. Eur. J., January 22, 2015, DOI: 10.1002/chem.201405410

Organocatalytic Enantioselective Decarboxylative Reaction of Malonic Acid Half Thioesters with Cyclic N-Sulfonyl Ketimines by Using N-Heteroarenesulfonyl Cinchona Alkaloid Amides

Lose to win: The organocatalytic enantioselective decarboxylative Mannich reaction of malonic acid half thioesters (MAHTs) with cyclic ketimines by using N-heteroarenesulfonyl cinchona alkaloid amides afforded products with high enantioselectivity (see scheme). Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. The reaction proceeds through a nucleophilic addition of the MAHTs to the ketimines prior to decarboxylation.

Chem. Eur. J., January 22, 2015, DOI: 10.1002/chem.201406270

Organocatalysis on Tap: Enantioselective Continuous Flow Processes Mediated by Solid-Supported Chiral Organocatalysts

Modern continuous flow techniques are reshaping the chemical landscape by providing tools for more efficient chemical processes. Enantioselective catalysis can also benefit from these advantages, and the combination of these two fields is a perfect match in terms of sustainable chemistry. Here we focus on the use of immobilized organocatalysts to promote enantioselective processes in flow.

Eur. J. Org. Chem., January 22, 2015, DOI: 10.1002/ejoc.201403042

Hugh Nakamura, Chihiro Tsukano, Motohiro Yasui, Shinsuke Yokouchi, Masayuki Igarashi, Yoshiji Takemoto
Total Synthesis of (−)-Caprazamycin A [Communication]

Total Synthesis of (−)-Caprazamycin A

Abra‘capraza’: Caprazamycin A has significant antibacterial activity against Mycobacterium tuberculosis (TB). The first total synthesis is herein reported and features the scalable preparation of the syn-β-hydroxy amino acid with a thiourea-catalyzed diastereoselective aldol reaction, construction of a diazepanone with an unstable fatty-acid side chain, and global deprotection with hydrogenation.

Angew. Chem. Int. Ed., January 22, 2015, DOI: 10.1002/anie.201411954

Ane Orue, Uxue Uria, Efraim Reyes, Luisa Carrillo, Jose L. Vicario
Catalytic Enantioselective [5+2] Cycloaddition between Oxidopyrylium Ylides and Enals under Dienamine Activation [Communication]

Catalytic Enantioselective [5+2] Cycloaddition between Oxidopyrylium Ylides and Enals under Dienamine Activation

By using all its powers of persuasion, a bifunctional secondary-amine/squaramide catalyst encouraged 1-acetoxyisochroman-4-ones to react as benzopyrylium ylides with α,β-unsaturated aldehydes in efficient [5+2] cycloaddition reactions with high diastereo- and enantioselectivity. The transformation proceeds by dienamine activation and involves β,γ-functionalization of the enal (see scheme).

Angew. Chem. Int. Ed., January 21, 2015, DOI: 10.1002/anie.201410723

Riccardo Porta, Maurizio Benaglia, Francesca Coccia, Franco Cozzi, Alessandra Puglisi
Solid Supported 9-Amino-9-deoxy-epi-quinine as Efficient Organocatalyst for Stereoselective Reactions in Batch and Under Continuous Flow Conditions [Communication]

Pankaj Chauhan, Suruchi Mahajan, Uğur Kaya, Daniel Hack, Dieter Enders
Bifunctional Amine-Squaramides: Powerful Hydrogen-Bonding Organocatalysts for Asymmetric Domino/Cascade Reactions [Review]

David Monge, Hao Jiang, Yolanda Alvarez-Casao
Masked Unsaturated Esters/Amides in Asymmetric Organocatalysis [Concept]

Masked Unsaturated Esters/Amides in Asymmetric Organocatalysis

Masked crusaders: This Concept article summarizes strategies regarding the use of masked unsaturated esters/amides in asymmetric organocatalysis (see scheme). Useful substrates are categorized by their inherent templates which enable interactions with organocatalysts and define their transformation back to the parent carboxylates. Examples showing the entire process (from substrates-to-functionalized esters/amides) are given.

Chem. Eur. J., January 9, 2015, DOI: 10.1002/chem.201405552

Electrodes Functionalized with the 2,2,6,6-Tetramethylpiperidinyloxy Radical for the Waste-Free Oxidation of Alcohols

Selective oxidation with electricity only: Electrodes functionalized with the organocatalyst 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) hold great potential for the development of the entirely waste-free industrial synthesis of valuable carbonyl compounds in the fine chemical and pharmaceutical industries.

ChemCatChem, January 8, 2015, DOI: 10.1002/cctc.201402896

Organocatalytic Asymmetric Cascade Reactions of 7-Vinylindoles: Diastereo- and Enantioselective Synthesis of C7-Functionalized Indoles

Cascade reactions of 7-vinylindoles: The first catalytic asymmetric cascade reaction of 7-vinylindoles has been established by the rational design of such substrates. Cascade reactions with isatin-derived 3-indolylmethanols catalyzed by chiral phosphoric acid (CPA; see scheme) allow the diastereo- and enantioselective synthesis of C7-functionalized indoles as well as the construction of cyclopenta[b]indole and spirooxindole frameworks (all >95:5 d.r., 94–>99 % ee).

Chem. Eur. J., December 17, 2014, DOI: 10.1002/chem.201405245

Nagaraju Mupparapu , Narsaiah Battini , Satyanarayana Battula , Shahnawaz Khan , Ram A. Vishwakarma , Qazi Naveed Ahmed 
Aminocatalytic Cross-Coupling Approach via Iminium Ions to Different C-C Bonds [Full Paper]

Aminocatalytic Cross-Coupling Approach via Iminium Ions to Different C-C Bonds

New iminium-ion reactivity mode: The reactivity of iminium ions containing an α C=O group, generated in situ by reaction of 2-oxoaldehydes with secondary amines, was developed and utilized to generate different cross-coupling products through formation of C-C and N-C bonds (see scheme). These processes proceed due to the unique ability of a three-component intermediate to undergo self-deamination and oxidation by air and, moreover, furnished the mildest possible approach to α-ketoamides.

Chem. Eur. J. 2015, 21, No. 07, 2954-2960

Michal Majek, Axel Jacobi von Wangelin
Metal-Free Carbonylations by Photoredox Catalysis [Communication]

Metal-Free Carbonylations by Photoredox Catalysis

A metal-free and base-free carbonylation has been developed which affords primary, secondary, and tertiary alkyl benzoates under irradiation with visible light in the presence of eosin Y as a photocatalyst. The mechanism has been studied by spectroscopic, theoretical, and preparative methods, and appears to involve intermediate aryl and aroyl radical species as well as a light-driven one-electron redox cycle without any sacrificial redox partner.

Angew. Chem. Int. Ed. 2015, 54, No. 07, 2270-2274

Solvent-Free One-Step Photochemical Hydroxylation of Benzene Derivatives by the Singlet Excited State of 2,3-Dichloro-5,6-dicyano-p-benzoquinone Acting as a Super Oxidant

Super photooxidant: Photoinduced hydroxylation of neat deaerated benzene derivatives to the corresponding phenols occurred under visible-light irradiation of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ; see figure), which acts as a super photooxidant in the presence of water. The reactions are initiated by electron-transfer oxidation of benzene derivatives with the singlet and triplet excited states of DDQ to form the corresponding radical cations and DDQ..

Chem. Eur. J. 2015, 21, No. 07, 2855-2861

Hong-Yu Wang, Kai Zhang, Chang-Wu Zheng, Zhuo Chai, Dong-Dong Cao, Jia-Xing Zhang, Gang Zhao
Asymmetric Dual-Reagent Catalysis: Mannich-type Reactions Catalyzed by Ion Pair [Communication]

Asymmetric Dual-Reagent Catalysis: Mannich-type Reactions Catalyzed by Ion Pair

Paired off: A new strategy combines a chiral phosphine with methyl acrylate to form a homogeneous ion pair. This activation mode has been successfully applied to Mannich-type reactions, thus generating a variety of fluorinated amino acid derivatives in high yields and with high ee values.

Angew. Chem. Int. Ed. 2015, 54, No. 06, 1775-1779

Mineto Uchiyama, Kotaro Satoh, Masami Kamigaito
Cationic RAFT Polymerization Using ppm Concentrations of Organic Acid [Communication]

Cationic RAFT Polymerization Using ppm Concentrations of Organic Acid

Cationic RAFTing: A cationic reversible addition–fragmentation chain-transfer (RAFT) polymerization with thiocarbonylthio compounds proceeds in the presence of a small amount of CF3SO3H. Various monomers including vinyl ethers as well as alkoxy- and hydroxystyrene can be used. A transformation from cationic to radical RAFT polymerization enables the synthesis of block copolymers between cationically and radically polymerizable monomers.

Angew. Chem. Int. Ed. 2015, 54, No. 06, 1924-1928

Brønsted Acid-Catalyzed, Highly Enantioselective Addition of Enamides to In Situ-Generated ortho-Quinone Methides: A Domino Approach to Complex Acetamidotetrahydroxanthenes

With excellent enantio- and diastereoselectivity, acetamido-substituted tetrahydrobenzoxanthenes and related heterocycles are obtained in one synthetic operation. A specifically optimized chiral phosphoric acid converts ortho-hydroxy benzhydryl alcohols and enamides into highly functionalized target compounds carrying three contiguous chiral centers with typically good overall yields.

Chem. Eur. J. 2015, 21, No. 06, 2348-2352

Hendrik Büttner, Kornelia Lau, Anke Spannenberg, Thomas Werner
Bifunctional One-Component Catalysts for the Addition of Carbon Dioxide to Epoxides [Full Paper]

Bifunctional One-Component Catalysts for the Addition of Carbon Dioxide to Epoxides

Couple up: Recyclable bifunctional ammonium salts are identified as one-component catalysts for the 100 % atom-economic coupling reaction of CO2 and epoxides even at 45 °C. The alcohol moiety that donates a hydrogen bond accelerates the catalytic reaction remarkably. This metal and solvent-free process can be performed on a multigram scale and is applied to the synthesis of a naturally occurring cyclic carbonate.

ChemCatChem 2015, 7, No. 03, 459-467

2-Furanylboronic Acid as an Effective Catalyst for the Direct Amidation of Carboxylic Acids at Room Temperature

Commercially available, inexpensive 2-furanylboronic acid has been identified as an effective catalyst for the direct dehydrative amide formation of carboxylic acids and amines. This transformation can be efficiently carried out at room temperature and is applicable to a wide range of carboxylic acids with primary and secondary amines to afford amides in good to excellent yields.

Eur. J. Org. Chem. 2015, No. 05, 1100-1107

Artificial Flavin Systems for Chemoselective and Stereoselective Oxidations

This review covers the design and applications of artificial flavinium-based organocatalytic systems for chemoselective and stereoselective oxygenations with hydrogen peroxide and oxygen as stoichiometric oxidising agents.

Eur. J. Org. Chem. 2015, No. 05, 915-932

Divergent Phosphine-Catalyzed [2+4] or [3+2] Cycloaddition Reactions of γ-Substituted Allenoates with Oxadienes

Dihydropyran and multifunctional cyclopentene derivatives are constructed from the same starting materials by using different phosphine catalysts. By controlling the nucleophilicity of the phosphine catalysts, the γ-substituted allenoates can selectively act as C3 or C2 synthons. The results suggest that the ethyl group of the γ-substituted allenoates plays a key role in the domino reaction.

Eur. J. Org. Chem. 2015, No. 04, 710-714

Marek Dzięgielewski, Jakub Pięta, Elżbieta Kamińska, Łukasz Albrecht
Organocatalytic Synthesis of Optically Active Organophosphorus Compounds [Microreview]

Organocatalytic Synthesis of Optically Active Organophosphorus Compounds

Organophosphorus reagents play pivotal roles in modern organic synthesis and have found many applications for the preparation both of synthetically important compounds and of biologically relevant ones. They are now widely employed in asymmetric organocatalysis to afford optically active organophosphorus compounds. This review summarizes recent progress in this field of enantioselective synthesis.

Eur. J. Org. Chem. 2015, No. 04, 677-702

Zhi-Qin Liang, Zhong-Hua Gao, Wen-Qiang Jia, Song Ye
Bifunctional N-Heterocyclic Carbene Catalyzed [3+4] Annulation of Enals and Aurones [Communication]

Bifunctional N-Heterocyclic Carbene Catalyzed [3+4] Annulation of Enals and Aurones

Stairway to seven: Bifunctional N-heterocyclic carbenes (NHCs) with a free hydroxy group are demonstrated as efficient catalysts for the [3+4] annulation of enals with aurones to give the corresponding benzofuran-fused ε-lactones in good yields with good diastereoselectivities and excellent enantioselectivities. Control experiments reveal that the [3+4] cycloadducts are kinetically favored and could be transformed to the thermodynamically favored [3+2] cycloadducts with a non-bifunctional NHC catalyst.

Chem. Eur. J. 2015, 21, No. 05, 1868-1872

Highly Enantioselective Intermolecular Cross Rauhut–Currier Reaction Catalyzed by a Multifunctional Lewis Base Catalyst

A cat. with handles: A multifunctional chiral Lewis base catalyst mediates the highly enantioselective intermolecular cross Rauhut–Currier (RC) reaction of different active olefins. The RC products were obtained in excellent yields and high chemo- and enantioselectivity. The reaction could be performed on a gram scale with a catalyst loading of 1 mol %.

Angew. Chem. Int. Ed. 2015, 54, No. 05, 1621-1624

A Practical Aryl Unit for Azlactone Dynamic Kinetic Resolution: Orthogonally Protected Products and A Ligation-Inspired Coupling Process

Squared away: A strategy for enantioselective azlactone dynamic kinetic resolution to generate orthogonally protected amino acids has been developed. In the presence of a squaramide-based catalyst, benzyl alcohol reacts with tetrachloroisopropoxycarbonyl-substituted azlactones to generate phthalimide products with excellent enantiocontrol. Removal of the phthalimide can be achieved in the presence of the ester and vice versa.

Angew. Chem. Int. Ed. 2015, 54, No. 03, 813-817

Phase-Transfer-Catalyzed Asymmetric SNAr Reaction of α-Amino Acid Derivatives with Arene Chromium Complexes

Increased substrate scope in phase-transfer-catalyzed asymmetric SNAr reactions was achieved by the use of arene chromium complexes as electrophiles. An efficient asymmetric synthesis of α,α-disubstituted α-amino acids containing various aromatic substituents is shown. PTC=phase-transfer catalyst.

Angew. Chem. Int. Ed. 2015, 54, No. 03, 838-840

Juho Bah, Veluru Ramesh Naidu, Johannes Teske, Johan Franzén
Carbocations as Lewis Acid Catalysts: Reactivity and Scope [Full Paper]

Asymmetric Synthesis of Fully Substituted Cyclopentane-Oxindoles through an Organocatalytic Triple Michael Domino Reaction

Triple Michael to pentagon! An organocatalytic three-component domino cyclization has been developed through a triple Michael sequence catalyzed by a secondary amine. Three bonds and six stereocenters, including a quaternary one, are formed by using equimolar reactants. A series of fully functionalized cyclopentane-oxindoles with potential bioactivity are obtained in good yields, very good diastereo-, and excellent enantioselectivities under mild conditions (see scheme).

Chem. Eur. J. 2015, 21, No. 03, 1004-1008

Asymmetric Dearomatization of β-Naphthols through an Amination Reaction Catalyzed by a Chiral Phosphoric Acid

Useful skeletons: An electrophilic amination reaction catalyzed by chiral phosphoric acid is the basis for a highly efficient asymmetric dearomatization of naphthols. This protocol provides functionalized β-naphthalenone compounds with a chiral quaternary carbon center in excellent yields and enantioselectivity. These motifs are found in various biologically active natural products and therapeutic reagents.

Angew. Chem. Int. Ed. 2015, 54, No. 02, 647-650

N-Heterocyclic Carbene Catalyzed Enantioselective α-Fluorination of Aliphatic Aldehydes and α-Chloro Aldehydes: Synthesis of α-Fluoro Esters, Amides, and Thioesters

Two roles for NFSI: The N-heterocyclic carbene (NHC) catalyzed asymmetric fluorination of readily available simple aliphatic aldehydes, α-chloro aldehydes, and even alcohols proceeds via azolium enolates and yields a wide range of α-fluoro esters, amides, and thioesters with excellent enantioselectivity. N-Fluorobenzenesulfonimide (NFSI) acts as both a fluorinating reagent and an oxidant in this transformation.

Angew. Chem. Int. Ed. 2015, 54, No. 02, 660-663

Joyram Guin, Qinggang Wang, Manuel van Gemmeren, Benjamin List
The Catalytic Asymmetric Abramov Reaction [Communication]

The Catalytic Asymmetric Abramov Reaction

A chiral disulfonimide catalyst is used to achieve the first catalytic enantioselective Abramov reaction. Several functionalized α-hydroxy phosphonates were synthesized in good yields and with excellent enantiomeric ratios of up to >99:1. The process was shown to be scalable and up to 1 g of starting material could be employed under mild reaction conditions.

Angew. Chem. Int. Ed. 2015, 54, No. 01, 355-358

Joshua M. Wieting, Thomas J. Fisher, Andrew G. Schafer, Michael D. Visco, Judith C. Gallucci, Anita E. Mattson
Preparation and Catalytic Activity of BINOL-Derived Silanediols [Full Paper]

Preparation and Catalytic Activity of BINOL-Derived Silanediols

A family of BINOL-derived enantiopure silanediols has been prepared and studied. The effect of the substitution pattern of the BINOL backbone on catalyst performance is detailed. The acidities and chloride binding constants are also reported for this new and exciting class of hydrogen-bond donor (HBD) catalysts.

Eur. J. Org. Chem. 2015, No. 03, 525-533

Zamani E. D. Cele, Per I. Arvidsson, Hendrik G. Kruger, Thavendran Govender, Tricia Naicker
Applied Enantioselective Aminocatalysis: α-Heteroatom Functionalization Reactions on the Carbapenem (β-Lactam Antibiotic) Core [Full Paper]

Applied Enantioselective Aminocatalysis: α-Heteroatom Functionalization Reactions on the Carbapenem (β-Lactam Antibiotic) Core

A carbapenem intermediate serves as a useful nucleophile in organocatalyst-mediated α-heterofunctionalization reactions leading to the formation of diverse products.

Eur. J. Org. Chem. 2015, No. 03, 638-646

Takeshi Yamada, Tomoyasu Hirose, Satoshi Omura, Toshiaki Sunazuka
Organocatalytic α-Addition of Isocyanides to Aldehydes [Short Communication]

Organocatalytic α-Addition of Isocyanides to Aldehydes

3,5,6-Trifluoro-2-pyridone is an efficient catalyst for the α-addition of isocyanides to aldehydes in the presence of water in benzene. Various aldehydes and isocyanides performed well in this reaction to provide the α-hydroxyamides. Even highly constrained substrates were well tolerated. This is the first example of pyridone-catalyzed α-addition of isocyanides.

Eur. J. Org. Chem. 2015, No. 02, 296-301

Michael H. Anthofer, Michael E. Wilhelm, Mirza Cokoja, Markus Drees, Wolfgang A. Herrmann, Fritz E. Kühn
Hydroxy-Functionalized Imidazolium Bromides as Catalysts for the Cycloaddition of CO2 and Epoxides to Cyclic Carbonates [Communication]

Hydroxy-Functionalized Imidazolium Bromides as Catalysts for the Cycloaddition of CO2 and Epoxides to Cyclic Carbonates

Just a matter of H bonding: The efficient valorization of carbon dioxide to cyclic carbonates was performed under mild and metal-free conditions by activation of the epoxide through hydrogen bonding of a hydroxyl-functionalized bisimidazolium salt.

ChemCatChem 2015, 7, No. 01, 94-98

Mohammed Kadraoui, Thibault Maunoury, Zoubir Derriche, Stéphane Guillarme, Christine Saluzzo
Isohexides as Versatile Scaffolds for Asymmetric Catalysis [Microreview]

Isohexides as Versatile Scaffolds for Asymmetric Catalysis

Two series of dianhydrohexitol derivatives, the first preserving the original bis-fused THF backbones and the second originating from single THF ring-opening reactions, are used as asymmetric ligands in organometallic catalysis or as asymmetric organocatalysts. Their synthesis and their application in different asymmetric reactions for the formation of C–H, C–C, C–N, and C–S bonds are discussed.

Eur. J. Org. Chem. 2015, No. 03, 441-457

Rongwei Jin, Frederic W. Patureau
Metal-free Dehydrogenative Isoquinolone Synthesis [Highlight]

Metal-free Dehydrogenative Isoquinolone Synthesis

Versatile C-H bonds: We discuss Manna and Antonchick's metal-free isoquinolone synthesis through the dehydrogenative condensation of benzamides with alkynes and what it means for the fields of C-H functionalization and organic synthesis. DG=Directing group, E=electrophile.

ChemCatChem 2015, 7, No. 02, 223-225

Supramolecular Encapsulation of Neutral Diazoacetate Esters and Catalyzed 1,3-Dipolar Cycloaddition Reaction by a Self-Assembled Hexameric Capsule

Stuck in the middle: Diazoacetate esters are suitable neutral guests for the self-assembled resorcin[4]arene hexameric capsule. The hydrogen-bonded supramolecular host efficiently catalyzes 1,3-dipolar cycloadditions between such substrates and electron-poor alkenes, which leads to 4,5-dihydro-1H-pyrazole derivatives. The presence of competitive cationic guests for the capsule confirms that the reaction occurs within the cavity.

ChemCatChem 2015, 7, No. 02, 291-296

Takasuke Mukaiyama, Kento Ogata, Tsuyoshi Ono, Yujiro Hayashi
Asymmetric Organocatalyzed Epoxidation of 2-Oxoindoline-3-ylidene Acetaldehydes [Full Paper]

Asymmetric Organocatalyzed Epoxidation of 2-Oxoindoline-3-ylidene Acetaldehydes

Giving metal catalysis the slip: The asymmetric epoxidation of 2-oxoindoline-3-ylidene acetaldehydes with hydrogen peroxide, catalyzed by diarylprolinol silyl ether, has been developed. Good to excellent diastereo- and enantioselectivities were realized even though the starting material 2-oxoindoline-3-ylidene acetaldehydes pre-existed as a mixture of E/Z-isomers.

ChemCatChem 2015, 7, No. 01, 155-159

Highly Enantioselective Michael Addition of 2-Fluoro-1,3-diketones to Nitroalkenes

The asymmetric synthesis of fluorinated 1,3-diketones is achieved through quinine–sulfonamide mediated asymmetric Michael addition of racemic 2-fluoro-1,3-diketones to nitroalkenes. Subsequent stereoselective reduction of the carbonyl groups led to a functionalized fluoroisostere of the triol and generation of four stereogenic carbon centers, including one quaternary center, in two reaction steps.

Eur. J. Org. Chem. 2015, No. 02, 320-324

A New Role for Sulfenate Anions: Organocatalysis

Introducing...Sulfenate! The sulfenate anion is introduced for the first time as a catalyst and was found to facilitate the conversion of benzyl halides to trans-stilbenes. CPME=Cyclopentyl methyl ether.

ChemCatChem 2015, 7, No. 02, 226-227

An Organocatalytic Process for the Hydrolytic Cleavage of Dithianes Mediated by Imidazolium Ions: No Harsh Agents Required

A new, organocatalytic approach to the hydrolytic deprotection of dithianes has been developed involving a low-toxicity imidazolium-ion-based catalyst in an aqueous medium.

Eur. J. Org. Chem. 2015, No. 01, 188-194

Enamine/Enolate-Mediated Organocatalytic Azide–Carbonyl [3+2] Cycloaddition Reactions for the Synthesis of Densely Functionalized 1,2,3-Triazoles

Organocatalytic click! Recent advances in the metal-free enamine/enolate-mediated azide–carbonyl [3+2] cycloaddition reaction are discussed. These approaches require neither a metal catalyst nor alkyne substrates. Owing to the ready availability of carbonyl compounds, these methods thus offer excellent alternatives for the synthesis of 1,4-/1,5-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles.

Angew. Chem. Int. Ed. 2014, 53, No. 52, 14310-14312

Rosaria Schettini, Brunello Nardone, Francesco De Riccardis, Giorgio Della Sala, Irene Izzo
Cyclopeptoids as Phase-Transfer Catalysts for the Enantioselective Synthesis of α-Amino Acids [Short Communication]

Cyclopeptoids as Phase-Transfer Catalysts for the Enantioselective Synthesis of α-Amino Acids

Cyclopeptoids are a novel class of efficient and tunable chiral macrocyclic phase-transfer catalyts. Screening of catalysts for the enantioselective alkylation of N-(diphenylmethylene)glycine tert-butyl ester shows the crucial role of N-arylmethyl residues.

Eur. J. Org. Chem. 2014, No. 35, 7793-7797

N-Heterocyclic Carbenes Supported on Vinylic Addition Polynorbornene: A Recyclable and Recoverable Organocatalyst

Three in one to ease organocatalysis: A robust, tunable, and recyclable organocatalytic system has been prepared by anchoring N-heterocyclic carbenes on an all-aliphatic vinylic addition polynorbornene (VA-PNB) scaffold. These three features make this heterogeneous NHC-based organocatalyst most convenient.

ChemCatChem 2014, 6, No. 12, 3547-3552

Promising Combination for Asymmetric Organocatalysis: Brønsted Acid-Assisted Chiral Phosphoric Acid Catalysis

Hand-in-hand: Recent developments in Brønsted acid-assisted chiral phosphoric acid catalysis are discussed, which exhibit the superiority of the self-assembly and the specificity of substrate recognition.

ChemCatChem 2014, 6, No. 12, 3309-3311

María D. Díaz-de-Villegas, José A. Gálvez, Ramón Badorrey, Pilar López-Ram-de-Víu
Organocatalysis in Enantioselective α-Functionalization of 2-Cyanoacetates [Review]

Applications of Carbohydrate-Based Organocatalysts in Enantioselective Synthesis

Carbohydrates, with their rigid backbones, large numbers of functional groups and high contents of chiral centres, are an appealing natural resource for the development of organocatalysts. They are becoming increasingly popular new tools for enantioselective synthesis, and this subject is reviewed for the period from 2009 to mid-2014.

Eur. J. Org. Chem. 2014, No. 33, 7291-7303

Charles C. J. Loh, Pankaj Chauhan, Daniel Hack, Christian Lehmann, Dieter Enders
Rapid Asymmetric Synthesis of Highly Functionalized Indanols via a Michael/Henry Organocascade with Submol% Squaramide Catalyst Loadings [Update]

Ophélie Quinonero, Cyril Bressy, Xavier Bugaut
Organocatalytic Enantioselective Construction of Polyaromatic Architectures [Highlight]

Organocatalytic Enantioselective Construction of Polyaromatic Architectures

Aromatics in 3D: Organocatalysis is now reaching beyond the control of stereogenic centers and opens new possibilities for the construction of complex polyaromatic structures with either helical or axial chirality.

Angew. Chem. Int. Ed. 2014, 53, No. 41, 10861-10863

Applications of Chiral Phosphine-Based Organocatalysts in Catalytic Asymmetric Reactions

Out with the old: The design and synthesis of new chiral phosphines, as well as their application in catalytic asymmetric reactions, have recently drawn a lot of attention. This review summarizes the advances in the field of enantioselective phosphine organocatalysis within the last couple of years.

Chem. Asian J. 2014, 9, No. 10, 2720-2734

Sylvain Oudeyer, Jean-François Brière, Vincent Levacher
Progress in Catalytic Asymmetric Protonation [Microreview]

Progress in Catalytic Asymmetric Protonation

This review provides an overview of recent advances in catalytic enantioselective protonation of preformed enol derivatives and catalytically generated enolates or equivalents through various cascade reaction sequences giving access to a large range of enantioenriched compounds containing tertiary stereocentres.

Eur. J. Org. Chem. 2014, No. 28, 6103-6119

Rebecca L. Davis, Julian Stiller, Tricia Naicker, Hao Jiang, Karl Anker Jørgensen
Asymmetric Organocatalytic Epoxidations: Reactions, Scope, Mechanisms, and Applications [Minireview]

Asymmetric Organocatalytic Epoxidations: Reactions, Scope, Mechanisms, and Applications

Pick your type: In the past several decades, highly useful epoxidation protocols have been developed with a variety of activation modes using a wide range of asymmetric organocatalysts. This review documents the rapid and expansive development in this area, thus providing a clear overview of the various catalyst types available for asymmetric organocatalytic epoxidations, as well as their mechanisms and applications.

Angew. Chem. Int. Ed. 2014, 53, No. 29, 7406-7426

Gloria Rassu, Vincenzo Zambrano, Luigi Pinna, Claudio Curti, Lucia Battistini, Andrea Sartori, Giorgio Pelosi, Giovanni Casiraghi, Franca Zanardi
Direct and Enantioselective Vinylogous Michael Addition of α-Alkylidenepyrazolinones to Nitroolefins Catalyzed by Dual Cinchona Alkaloid Thioureas [Update]

Catalytic Asymmetric α-Hydroxyamination of Carbonyls with N-Hydroxycarbamates Becomes Greener

The power of two: A highly enantio- and regioselective aminocatalytic and Lewis acid catalyzed α-hydroxyamination of β-keto esters and 1,3-diketones with N-hydroxycarbamates is realized in “one-pot” under aerobic conditions. The powerful dual catalysis strategy opens opportunities for developing new efficient organic transformations. Cbz=Benzyloxycarbonyl, Boc=tert-butoxycarbonyl.

ChemCatChem 2014, 6, No. 07, 1863-1865

Tyler J. Auvil, Andrew G. Schafer, Anita E. Mattson
Design Strategies for Enhanced Hydrogen-Bond Donor Catalysts [Microreview]

Design Strategies for Enhanced Hydrogen-Bond Donor Catalysts

Since initial reports of organocatalysis through hydrogen bonding interactions, a number of strategies have emerged to allow access to enhanced hydrogen-bond donor (HBD) organocatalysts. These strategies range from augmentation of existing HBDs to the design and synthesis of new HBD catalysts. The effects of recent dual HBD designs on catalyst performance are described.

Eur. J. Org. Chem. 2014, No. 13, 2633-2646

Organocatalytic β-Functionalization of Saturated Carbonyl Compounds—the State of the Art

Get straight to the point! The elusive and direct organocatalytic β-functionalization of saturated carbonyl compounds has been tackled by oxidative enamine catalysis, oxidative NHC catalysis and merging of photoredox catalysis with organocatalysis. This new activation mode expanded the horizons of chemical synthesis and offers new insight for organic transformations and complex molecule synthesis.

ChemCatChem 2014, 6, No. 05, 1183-1185

Yao Li, Xin Li, Jin-Pei Cheng
Catalytic Asymmetric Synthesis of Chiral Benzofuranones [Review]

The Alternative Route to Enantiopure Multicomponent Reaction Products: Biocatalytic or Organocatalytic Enantioselective Production of Inputs for Multicomponent Reactions

This review describes an approach to enantiopure products based on the enantioselective generation, through biocatalysis or organocatalysis, of chiral substrates for a multicomponent reaction (MCR). If the chiral substrates are able to control the newly formed stereogenic centers, this strategy allows fast and diversity-oriented entry to complex chiral substrates.

Eur. J. Org. Chem. 2014, No. 10, 2005-2015

Andrea Gualandi, Luca Mengozzi, Claire M. Wilson, Pier Giorgio Cozzi
Synergy, Compatibility, and Innovation: Merging Lewis Acids with Stereoselective Enamine Catalysis [Focus Review]

Synergy, Compatibility, and Innovation: Merging Lewis Acids with Stereoselective Enamine Catalysis

The Perfect Storm! Water facilitates catalyst turnover in enamine organocatalysis, and it is generated during enamine formation. A synergy between Lewis acids and organocatalysts allows for the development of new, selective, and innovative processes, but water-compatible Lewis acids must be employed that are capable of surviving and maintaining activity in the presence of water.

Chem. Asian J. 2014, 9, No. 04, 984-995

Chiral 1,1'-Binaphthyl-2,2'-Disulfonic Acid (BINSA) and Its Derivatives for Asymmetric Catalysis

BINSA, done that: The Brønsted acidity of catalysts is considered to be associated with their catalytic activity. Therefore, chiral 1,1'-binaphthyl-2,2-disulfonic acid (BINSA) has recently received much attention as a strong chiral Brønsted acid catalyst. This Focus Review summarizes the latest achievements in chiral BINSA chemistry from the perspective of their synthesis and their catalytic use in asymmetric organocatalysis.

Asian J. Org. Chem. 2014, 3, No. 04, 352-365

Suqing Zheng, Casi M. Schienebeck, Wei Zhang, Hao-Yuan Wang, Weiping Tang
Cinchona Alkaloids as Organocatalysts in Enantioselective Halofunctionalization of Alkenes and Alkynes [Focus Review]

Cinchona Alkaloids as Organocatalysts in Enantioselective Halofunctionalization of Alkenes and Alkynes

You say goodbye, I say halo: Derivatives of cinchona alkaloids are an important class of organocatalysts. Their applications in asymmetric halofunctionalization of alkenes and alkynes are summarized in this Focus Review. A wide range of nucleophiles, halogenation reagents, and substituted alkenes, alkynes, or enynes can participate in these reactions to afford diverse chiral building blocks.

Asian J. Org. Chem. 2014, 3, No. 04, 366-376

Frédéric-Georges Fontaine, Marc-André Courtemanche, Marc-André Légaré
Transition-Metal-Free Catalytic Reduction of Carbon Dioxide [Concept]

Transition-Metal-Free Catalytic Reduction of Carbon Dioxide

Less is more: Metal-free systems, including frustrated Lewis pairs (FLPs), have been shown to bind CO2. By reducing the Lewis acidity and basicity of the ambiphilic system, it is possible to generate active catalysts for the deoxygenative hydroboration of carbon dioxide to methanol derivatives with conversion rates comparable to those of transition-metal-based catalysts (see scheme).

Chem. Eur. J. 2014, 20, No. 11, 2990-2996

Haiying Du, Jean Rodriguez, Xavier Bugaut, Thierry Constantieux
Organocatalytic Enantioselective Multicomponent Synthesis of Pyrrolopiperazines [Update]

N-Heterocyclic Carbene Catalyzed Activation of Esters: A New Option for Asymmetric Domino Reactions

Esters—what else! A new strategy in NHC organocatalysis allows the α-, β- and γ-activation of saturated and unsaturated esters. The resulting acyl azolium intermediates efficiently participate in domino reactions with suitable substrates to generate synthetically valuable carbo- and heterocycles with very good diastereo- and excellent enantioselectivities.

Angew. Chem. Int. Ed. 2014, 53, No. 06, 1485-1487

© Wiley-VCH 2013.