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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

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Juhua Feng, Lili Lin, Kunru Yu, Xiaohua Liu, Xiaoming Feng
Asymmetric Synthesis of Dihydrofurans via Organocatalytic Domino Michael–Alkylation Reaction [Update]

Anitha Alanthadka, C. Uma Maheswari
N-Heterocyclic Carbene-Catalyzed Oxidative Amidation of Aldehydes with Amines [Communication]

Daniel Janssen-Müller, Michael Schedler, Mirco Fleige, Constantin G. Daniliuc, Frank Glorius
Enantioselective Intramolecular Hydroacylation of Unactivated Alkenes: An NHC-Catalyzed Robust and Versatile Formation of Cyclic Chiral Ketones [Communication]

Enantioselective Intramolecular Hydroacylation of Unactivated Alkenes: An NHC-Catalyzed Robust and Versatile Formation of Cyclic Chiral Ketones

100 % Organic: A highly enantioselective N-heterocyclic carbene (NHC)-catalyzed intramolecular hydroacylation of aromatic and, more interestingly, aliphatic aldehydes with unactivated olefins offers access to a range of cyclic α-chiral ketones bearing quaternary centers. The reaction was found to be highly robust and proceeds with excellent yield in the presence of a diverse range of functional groups.

Angew. Chem. Int. Ed., March 16, 2015, DOI: 10.1002/anie.201412302

Lorenzo Caruana, Martina Mondatori, Vasco Corti, Sara Morales, Andrea Mazzanti, Mariafrancesca Fochi, Luca Bernardi
Catalytic Asymmetric Addition of Meldrum’s Acid, Malononitrile and 1,3-Dicarbonyls to ortho-Quinone Methides Generated In Situ Under Basic Conditions [Communication]

Catalytic Asymmetric Addition of Meldrum’s Acid, Malononitrile and 1,3-Dicarbonyls to ortho-Quinone Methides Generated In Situ Under Basic Conditions

Challenging substrates: The generation in situ of ortho-quinone methides (o-QMs) through sulfinic acid elimination was combined for the first time with an organocatalytic process (see scheme). This combination allowed the engagement of sensitive and unstable o-QMs in asymmetric reactions with active methylene compounds, under the promotion of bifunctional catalysts, giving access to 2,3-dihydrocoumarins, 4H-chromenes and xanthen-1-ones.

Chem. Eur. J., March 12, 2015, DOI: 10.1002/chem.201500710

Catalytic Asymmetric Arylation of 3-Indolylmethanols: Enantioselective Synthesis of 3,3'-Bis(indolyl)oxindoles with High Atom Economy

Shifting economy: The catalytic enantioselective arylation of 3-indolylmethanols has been established in an atom-economic fashion, which assembles isatin-derived 3-indolylmethanols and 3-methylindoles into biologically important 3,3'-bis(indolyl)oxindoles bearing a quaternary stereogenic center in high yields and good enantioselectivities [≈99 % yield and 91:9 enantiomeric ratio (er)]. CPA=Chiral phosphoric acid.

ChemCatChem, March 10, 2015, DOI: 10.1002/cctc.201500093

Pyrimidine-Derived Prolinamides as Recoverable Bifunctional Organocatalysts for Enantioselective Inter- and Intramolecular Aldol Reactions under Solvent-Free Conditions

The intermolecular ketone–aldehyde and aldehyde–aldehyde aldol reactions and the Hajos–Parrish–Eder–Sauer–Wiechert versions with the employment of chiral L-prolinamides containing the (R,R)- and (S,S)-trans-cyclohexane-1,2-diamine scaffold and a 2-pyrimidinyl unit are successfully performed under solvent-free conditions; WMK = Wieland–Miescher ketone.

Eur. J. Org. Chem., March 6, 2015, DOI: 10.1002/ejoc.201500007

Maxime Gicquel, Yang Zhang, Paul Aillard, Pascal Retailleau, Arnaud Voituriez, Angela Marinetti
Phosphahelicenes in Asymmetric Organocatalysis: [3+2] Cyclizations of γ-Substituted Allenes and Electron-Poor Olefins [Communication]

Phosphahelicenes in Asymmetric Organocatalysis: [3+2] Cyclizations of γ-Substituted Allenes and Electron-Poor Olefins

Helical P: Specially designed phosphahelicenes demonstrate high efficiency and enantioselectivity in organocatalytic cyclizations. These new helically chiral phosphines complement and outperform previous nucleophilic catalysts used in this field. Ipc*=(1R,2R,3R,5S)-2,6,6-trimethyl-bicyclo[3.1.1]-heptan-3-yl.

Angew. Chem. Int. Ed., March 5, 2015, DOI: 10.1002/anie.201500299

Rajesh Munirathinam, Jurriaan Huskens, Willem Verboom
Supported Catalysis in Continuous-Flow Microreactors [Review]

Design and Synthesis of Chiral Binaphthol-Derived Bisphosphoric Acids and Their Application in the Catalytic Enantioselective Hydrogenation of Quinolines

A little of bis, a little of that: A number of new chiral bisphosphoric acids were developed starting from (R)-BINOL. Rigid cyclic phosphamide and phosphonate components were converted into bisphosphoric acids, in contrast to the traditional BINOL-based phosphoric acids with only phosphonate motifs.

Asian J. Org. Chem., March 3, 2015, DOI: 10.1002/ajoc.201500020

María de Gracia Retamosa, Abel de Cózar, Mirian Sánchez, José I. Miranda, José M. Sansano, Luis M. Castelló, Carmen Nájera, Ana I. Jiménez, Francisco J. Sayago, Carlos Cativiela, Fernando P. Cossío
Remote Substituent Effects on the Stereoselectivity and Organocatalytic Activity of Densely Substituted Unnatural Proline Esters in Aldol Reactions [Full Paper]

Remote Substituent Effects on the Stereoselectivity and Organocatalytic Activity of Densely Substituted Unnatural Proline Esters in Aldol Reactions

Densely substituted enantiopure proline esters obtained through [3+2] cycloadditions catalyze aldol reactions. These synthetic organocatalysts produce different enantiomeric aldol adducts depending on the stereochemical dispositions of the substituents at distal positions with respect to the catalytic site. Design criteria are proposed for this kind of organocatalysts.

Eur. J. Org. Chem., March 3, 2015, DOI: 10.1002/ejoc.201500160

Jianfeng Xu, Xingkuan Chen, Ming Wang, Pengcheng Zheng, Bao-An Song, Yonggui Robin Chi
Aminomethylation of Enals through Carbene and Acid Cooperative Catalysis: Concise Access to β2-Amino Acids [Communication]

Aminomethylation of Enals through Carbene and Acid Cooperative Catalysis: Concise Access to β2-Amino Acids

Harmonious cooperation: An N-heterocyclic carbene (NHC) and (in situ generated) Brønsted acid cooperatively catalyze the aminomethylation of α,β-unsaturated aldehydes. This cooperative catalytic reaction provides a redox neutral strategy for quick access to β2-amino esters in an enantioselective manner.

Angew. Chem. Int. Ed., March 3, 2015, DOI: 10.1002/anie.201412132

Qiying Zhang, Xiuling Cui, Long Zhang, Sanzhong Luo, Hui Wang, Yangjie Wu
Redox Tuning of a Direct Asymmetric Aldol Reaction [Communication]

Redox Tuning of a Direct Asymmetric Aldol Reaction

Stay tuned: A redox tuning strategy has been developed for asymmetric aminocatalysis using a chiral ferrocenophane. Under redox control, the catalyst catalyzes the asymmetric aldol reaction at room temperature with excellent yield and good stereoselectivity. Moreover, the catalyst is recyclable.

Angew. Chem. Int. Ed., February 27, 2015, DOI: 10.1002/anie.201500070

Adam D. Gammack Yamagata, Swarup Datta, Kelvin E. Jackson, Linus Stegbauer, Robert S. Paton, Darren J. Dixon
Enantioselective Desymmetrization of Prochiral Cyclohexanones by Organocatalytic Intramolecular Michael Additions to α,β-Unsaturated Esters [Communication]

Enantioselective Desymmetrization of Prochiral Cyclohexanones by Organocatalytic Intramolecular Michael Additions to α,β-Unsaturated Esters

Enantioenriched derivatives of 2-azabicyclo[3.3.1]nonane, a key motif common to many alkaloids, are obtained by a catalytic asymmetric desymmetrization reaction with a cyclohexanediamine-derived primary-amine organocatalyst. A range of prochiral cyclohexanone derivatives with an α,β-unsaturated ester moiety linked to the 4-position afford the bicyclic products as single diastereoisomers in high enantioselectivity and good yields.

Angew. Chem. Int. Ed., February 27, 2015, DOI: 10.1002/anie.201411924

Wengang Guo, Bo Wu, Xin Zhou, Ping Chen, Xu Wang, Yong-Gui Zhou, Yan Liu, Can Li
Formal Asymmetric Catalytic Thiolation with a Bifunctional Catalyst at a Water–Oil Interface: Synthesis of Benzyl Thiols [Communication]

Formal Asymmetric Catalytic Thiolation with a Bifunctional Catalyst at a Water–Oil Interface: Synthesis of Benzyl Thiols

Phased out: A squaramide organocatalyst mediates the asymmetric synthesis of α-aryl- and α-alkyl-substituted benzyl mercaptans through the thiolation of in situ generated ortho-quinone methides at a water–oil interface. The reactions exhibit wide substrate scope and excellent enantioselectivity because of the spatial separation of the inorganic base in the aqueous phase from the chiral components in the organic phase.

Angew. Chem. Int. Ed., February 18, 2015, DOI: 10.1002/anie.201409894

Catalytic Asymmetric Inverse-Electron-Demand Oxa-Diels–Alder Reaction of In Situ Generated ortho-Quinone Methides with 3-Methyl-2-Vinylindoles

Three in a row: The title reaction of ortho-quinone methides, generated in situ from ortho-hydroxybenzyl alcohols, has been established. By selecting 3-methyl-2-vinylindoles as a class of competent dienophiles, this approach provides an efficient strategy to construct enantioenriched chroman frameworks with three adjacent stereogenic centers in high yields and excellent stereoselectivities. CPA=chiral phosphoric acid.

Angew. Chem. Int. Ed., February 18, 2015, DOI: 10.1002/anie.201500215

Nicola Armenise, Stefano Dughera, Andrea Gualandi, Luca Mengozzi, Margherita Barbero, Pier Giorgio Cozzi
Organocatalyzed Asymmetric Alkylation of Stable Aryl or Heteroaryl(3-indolyl)methylium o-Benzenedisulfonimides [Full Paper]

Organocatalyzed Asymmetric Alkylation of Stable Aryl or Heteroaryl(3-indolyl)methylium o-Benzenedisulfonimides

Steady as she goes: Stable indolyl carbenium salts have been employed in the direct alkylation of aldehydes. Excellent enantiomeric excesses and good diastereomeric ratios were obtained using a number of aryl or heteroaryl(3-indolyl)carbenium ions as the highly stable o-benzenedisulfonimide salts and with the reaction promoted by the Hayashi–Jørgensen catalyst.

Asian J. Org. Chem., February 10, 2015, DOI: 10.1002/ajoc.201402275

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

Huanrui Zhang, Baomin Wang, Longchen Cui, Xiaoze Bao, Jingping Qu, Yuming Song
Organocatalytic Asymmetric Fluorination of 4-Substituted Isoxazolinones [Short Communication]

Organocatalytic Asymmetric Fluorination of 4-Substituted Isoxazolinones

A straightforward method for the asymmetric fluorination of 4-substituted isoxazolinones catalyzed by a bis-cinchona alkaloid catalyst was developed. A series of 4-fluoroisoxazolinone derivatives with a fluorine-containing quaternary stereocenter were obtained in good to high yields with good enantioselectivities (up to 91 % yield, 85 % ee).

Eur. J. Org. Chem. 2015, No. 10, 2143-2147

An NHC-Catalyzed In Situ Activation Strategy to β-Functionalize Saturated Carboxylic Acid: An Enantioselective Formal [3+2] Annulation for Spirocyclic Oxindolo-γ-butyrolactones

Top cat: An in situ N-heterocyclic carbene (NHC)-catalyzed activation strategy to β-functionalize saturated carboxylic acid was developed (see scheme). This asymmetric formal [3+2] annulation delivered spirocyclic oxindolo-γ-butyrolactones from saturated carboxylic acid and isatin in good yields with high to excellent enantioselectivities. The availability of the starting materials, direct installation of functional units at unreactive carbon atom and the convergent assembly make this protocol attractive for organic synthesis.

Chem. Eur. J. 2015, 21, No. 14, 5355-5359

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. 2015, 54, No. 14, 4264-4268

One-Pot Synthesis of O-Allylhydroxylamines through the Organocatalytic Oxidation of Tertiary Allylic Amines Followed by a [2,3]-Meisenheimer Rearrangement

All in one pot: The organocatalytic oxidation of tertiary allylic amines followed by a Meisenheimer rearrangement leads to protected hydroxylamines (see scheme).

Chem. Eur. J. 2015, 21, No. 13, 5238-5241

Mareike C. Holland, Ryan Gilmour
Deconstructing Covalent Organocatalysis [Minireview]

Deconstructing Covalent Organocatalysis

In recent years, interest in organocatalytic intermediates has intensified. Through their study, various mechanistic anomalies have been illuminated, new reaction manifolds have been identified, and the intermediates themselves have proven to be valuable platforms for the study of many noncovalent interactions more commonly found in complex biomolecules. Cat=catalyst, P=product, S=substrate.

Angew. Chem. Int. Ed. 2015, 54, No. 13, 3862-3871

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. 2015, 21, No. 12, 4518-4522

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. 2015, 21, No. 12, 4494-4504

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. 2015, 54, No. 11, 3216-3221

Lucia Anna Bivona, François Quertinmont, Hazi Ahmad Beejapur, Francesco Giacalone, Mireia Buaki-Sogo, Michelangelo Gruttadauria, Carmela Aprile
Thiazolium-Based Catalysts for the Etherification of Benzylic Alcohols under Solvent-Free Conditions [Full Paper]

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 synthons, which readily undergo asymmetric intermolecular 1,4-dipolar spiroannulations with isatylidenemalononitrile in the presence of an amino acid derived chiral phosphine catalyst (TP7) to furnish enantioenriched 3-spirocyclohexenone 2-oxindoles in good yields with up to 87 % ee.

Chem. Eur. J. 2015, 21, No. 11, 4224-4228

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

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. 2015, 21, No. 10, 3929-3932

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. 2015, 54, No. 10, 3043-3046

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 by hydrogenation.

Angew. Chem. Int. Ed. 2015, 54, No. 10, 3136-3139

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. 2015, 21, No. 10, 3933-3936

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. 2015, No. 09, 1995-2004

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. 2015, No. 08, 1745-1753

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. 2015, No. 09, 2030-2037

Davide Ravelli, Maurizio Fagnoni
Aromatic Aldehydes as Energy-Transfer Photoorganocatalysts [Highlight]

Aromatic Aldehydes as Energy-Transfer Photoorganocatalysts

New photochemical life of ArCHO: The recent breakthrough discovery by Melchiorre and co-workers in the use of aromatic aldehydes as energy-transfer photoorganocatalysts in atom-transfer radical addition reactions is discussed. ISC=Intersystem crossing; X=I, Br, Cl.

ChemCatChem 2015, 7, No. 05, 735-737

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. 2015, No. 08, 1834-1839

Yeong-Jiunn Jang, Yu-Shan Chen, Chia-Jui Lee, Chi-Han Chen, Ganapuram Madhusudhan Reddy, Chi-Ting Ko, Wenwei Lin
Asymmetric Organocatalytic Synthesis of Highly Substituted Cyclohexenols by Domino Double-Michael Reactions of 1-Hydroxy-1,4-dien-3-ones and 2-Alkylidenemalononitriles [Full Paper]

Asymmetric Organocatalytic Synthesis of Highly Substituted Cyclohexenols by Domino Double-Michael Reactions of 1-Hydroxy-1,4-dien-3-ones and 2-Alkylidenemalononitriles

An effective asymmetric organocatalytic synthesis of polysubstituted cyclohexenes from 1-hydroxy-1,4-dien-3-ones and 2-alkylidenemalononitriles by a domino double-Michael reaction sequence using quinine as catalyst has been achieved. The products were obtained in moderate-to-good yields (up to 96 %) and enantioselectivities (up to 92 % ee).

Eur. J. Org. Chem. 2015, No. 09, 2066-2074

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 2015, 7, No. 05, 830-835

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 (Pro) units results in highly active and selective organocatalysts for aldol reactions in water (see scheme; BTA=benzene-1,3,5-tricarboxamide).

Chem. Eur. J. 2015, 21, No. 09, 3682-3690

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

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]

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

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. 2015, No. 06, 1173-1188

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 2015, 7, No. 04, 552-558

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

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

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

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

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

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.