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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]

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.

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Diterpenoid Alkaloid Lappaconine Derivative Catalyzed Asymmetric α-Hydroxylation of β-Dicarbonyl Compounds with Hydrogen Peroxide

Ten new organocatalysts derived from the diterpenoid alkaloid lappaconitine are described. Activities for the enantioselective α-hydroxylation of β-dicarbonyl compounds with 30 % hydrogen peroxide as a green and practical source of oxygen is described. This protocol allows convenient access to the corresponding α-hydroxy-β-dicarbonyl compounds with up to 98 % yield and 92 % ee under mild conditions.

Eur. J. Org. Chem., Apr 17, 2014, DOI: 10.1002/ejoc.201402019

Nandini Vallavoju, Sermadurai Selvakumar, Steffen Jockusch, Mukund P. Sibi, Jayaraman Sivaguru
Enantioselective Organo-Photocatalysis Mediated by Atropisomeric Thiourea Derivatives [Communication]

Enantioselective Organo-Photocatalysis Mediated by Atropisomeric Thiourea Derivatives

Organo-photocatalysts that are based on atropisomeric thioureas and display lower excited-state energies than the reactive substrates have been developed. These photocatalysts were found to be efficient in promoting the [2+2] photocycloaddition of 4-alkenyl-substituted coumarins, which led to the corresponding products with high enantioselectivity (77–96 % ee) at low catalyst loading (1–10 mol %).

Angew. Chem. Int. Ed., Apr 16, 2014, DOI: 10.1002/anie.201310940

Seiji Shirakawa, Lijia Wang, Rongjun He, Satoru Arimitsu, Keiji Maruoka
A Base-Free Neutral Phase-Transfer Reaction System [Full Paper]

A Base-Free Neutral Phase-Transfer Reaction System

In and out of phase: The mechanism of a novel base-free neutral phase-transfer reaction system was investigated (see scheme). The aqueous–organic biphasic reaction system with lipophilic tetraalkylammonium bromide was essential to promote the neutral phase-transfer reactions. The base-free reaction system could be applied to several asymmetric reactions.

Chem. Asian J., Apr 15, 2014, DOI: 10.1002/asia.201402194

Lisa Kötzner, Matthew J. Webber, Alberto Martínez, Claudia De Fusco, Benjamin List
Asymmetric Catalysis on the Nanoscale: The Organocatalytic Approach to Helicenes [Communication]

Asymmetric Catalysis on the Nanoscale: The Organocatalytic Approach to Helicenes

Twisting indoles: A novel chiral Brønsted acid, specifically designed for long-range control on a nanoscale, catalyzes the asymmetric synthesis of azahelicenes through a Fischer indolization. The method has the advantage of starting from simple achiral starting materials, which can be modified by changing the protecting group (R2) or the terminal substituents (R1, R3). The products can be further oxidized to polyaromatic systems.

Angew. Chem. Int. Ed., Apr 15, 2014, DOI: 10.1002/anie.201400474

Ureidopeptide-Based Brønsted Bases: Design, Synthesis and Application to the Catalytic Enantioselective Synthesis of β-Amino Nitriles from (Arylsulfonyl)acetonitriles

Learning from peptides: A concise route for the catalytic enantioselective synthesis of β-amino nitriles has been achieved by using ureidopeptide-based Brønsted bases as catalysts in the Mannich reaction of N-Boc imines and (arylsulfonyl)acetonitriles (see scheme; Boc=tert-butoxycarbonyl, napht=naphthyl, TMS=trimethylsilyl).

Chem. Eur. J., Apr 15, 2014, DOI: 10.1002/chem.201304877

Qijian Ni, Xiaoxiao Song, Gerhard Raabe, Dieter Enders
N-Heterocyclic Carbene-Catalyzed Enantioselective Annulation of Indolin-3-ones with Bromoenals [Communication]

N-Heterocyclic Carbene-Catalyzed Enantioselective Annulation of Indolin-3-ones with Bromoenals

More NHC-organocatalysis: N-Heterocyclic carbene-catalyzed reactions of indolin-3-ones with 2-bromoenals opened an asymmetric access to 3,4-dihydropyrano[3,2-b]indol-2(5 H)-ones in good yields and with good to excellent enantioselectivities. This protocol tolerates a broad substrate scope. In addition, a possible mechanism for the annulation reaction is presented.

Chem. Asian J., Apr 11, 2014, DOI: 10.1002/asia.201402052

Neighboring ortho-Hydroxy Group Directed Catalytic Asymmetric Triple Domino Reactions of Acetaldehyde with (E)-2-(2-Nitrovinyl)phenols

The utilization of neighboring ortho-hydroxy group participation in the pretransition state of enamine/iminium-based triple domino Michael/aldol/oxa-Michael reactions catalyzed by (R)-DPPOTMS followed by Wittig and Michael/Wittig–Horner reactions is described. Enantiomerically pure chromanes and tetrahydro-6H-benzo[c]chromenes having three to four contiguous stereocenters are synthesized.

Eur. J. Org. Chem., Apr 10, 2014, DOI: 10.1002/ejoc.201402182

Ai-Bao Xia, Chao Wu, Tao Wang, Yan-Peng Zhang, Xiao-Hua Du, Ai-Guo Zhong, Dan-Qian Xu, Zhen-Yuan Xu
Enantioselective Cascade Oxa-Michael–Michael Reactions of 2-Hydroxynitrostyrenes with Enones Using a Prolinol Thioether Catalyst [Communication]

Julien Brioche, Thibaut Courant, Lilian Alcarez, Mark Stocks, Mark Furber, Jieping Zhu, Géraldine Masson
Chiral Phosphoric Acid-Catalyzed Enantioselective Three- Component Aza-Diels–Alder Reactions of Aminopyrroles and Aminopyrazoles [Communication]

Cascade Olefin Isomerization/Intramolecular Diels–Alder Reaction Catalyzed by N-Heterocyclic Carbenes

NHC-catalyzed cascade: The addition of an N-heterocyclic carbene (NHC) to the carbonyl group of an α,β,γ,δ-unsaturated enol ester affords a hemiacetal azolium intermediate that enables a cascade olefin isomerization/Diels–Alder reaction. Preliminary studies into the utility of the products using reductive and oxidative cleavage gave substrates for potential use in the synthesis of complex targets.

Angew. Chem. Int. Ed., Apr 06, 2014, DOI: 10.1002/anie.201402067

Eeva K. Kemppainen, Gokarneswar Sahoo, Antti Piisola, Andrea Hamza, Bianka Kótai, Imre Pápai, Petri M. Pihko
Mukaiyama–Michael Reactions with Trans-2,5-Diarylpyrrolidine Catalysts: Enantioselectivity Arises from Attractive Noncovalent Interactions, Not from Steric Hindrance [Full Paper]

Mukaiyama–Michael Reactions with Trans-2,5-Diarylpyrrolidine Catalysts: Enantioselectivity Arises from Attractive Noncovalent Interactions, Not from Steric Hindrance

Embraced enantioselectivity: Mukaiyama–Michael reactions catalyzed by trans-2,5-diphenylpyrrolidine catalyst are highly enantioselective, but why? The answer appears to lie in the attractive, not repulsive, noncovalent interactions in the transition states leading to the major product(s) (see scheme; TIPS=triisopropylsilyl).

Chem. Eur. J., Apr 01, 2014, DOI: 10.1002/chem.201304240

Bianka Kótai, György Kardos, Andrea Hamza, Viktor Farkas, Imre Pápai, Tibor Soós
On the Mechanism of Bifunctional Squaramide-Catalyzed Organocatalytic Michael Addition; Protonated Catalyst as an Oxyanion Hole [Full Paper]

On the Mechanism of Bifunctional Squaramide-Catalyzed Organocatalytic Michael Addition; Protonated Catalyst as an Oxyanion Hole

Finding the path: The mechanism of bifunctional squaramide-promoted Michael addition of prochiral 1,3-dioxo nucleophiles and nitroolefin has been studied on the basis of DFT calculations. Among the investigated mechanistic scenarios, the pathway corresponding to electrophile activation via the protonated amine unit is found to be the most feasible (see figure). For some of the minor stereoisomeric products, alternative pathways are also accessible.

Chem. Eur. J., Mar 27, 2014, DOI: 10.1002/chem.201304553

Ning Li, Guo-Gui Liu, Jian Chen, Feng-Feng Pan, Bing Wu, Xing-Wang Wang
Regio- and Enantioselective Organocascade Michael–Michael Reactions: Construction of Chiral Trisubstituted Indanes [Short Communication]

Regio- and Enantioselective Organocascade Michael–Michael Reactions: Construction of Chiral Trisubstituted Indanes

An organocatalytic regio- and enantioselective cascade conjugate addition reaction is developed for the construction of enantiomerically enriched 1,2,3-trisubstituted indanes. The resulting indane derivatives can be readily converted into optically active (1-indanylmethyl)amine and tetrahydroindeno[2,1-b]pyrrole derivatives. Boc = tert-butoxycarbonyl.

Eur. J. Org. Chem., Mar 27, 2014, DOI: 10.1002/ejoc.201301860

Construction of Chiral Bridged Tricyclic Benzopyrans: Enantioselective Catalytic Diels–Alder Reaction and a One-Pot Reduction/Acid-Catalyzed Stereoselective Cyclization

The old one-two: A two-step synthetic strategy was developed for the construction of the bridged benzopyran core present in many natural products. It consisted of an efficient asymmetric catalytic decarboxylative Diels–Alder reaction between enals and coumarin-3-carboxylic acids, and a one-pot protocol for the reduction/acid-catalyzed stereoselective cyclization. TBS=tert-butyldimethylsilyl.

Angew. Chem. Int. Ed., Mar 26, 2014, DOI: 10.1002/anie.201402170

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., Mar 21, 2014, DOI: 10.1002/ejoc.201400035

One-Pot Organocatalytic Enantioselective Michael/Povarov Domino Strategy for the Construction of Spirooctahydroacridine-3,3'-oxindole Scaffolds

Domino construction: An efficient organocatalytic one-pot domino Michael/intramolecular Povarov reaction has been developed to provide enantiomerically enriched spirooctahydroacridine-3,3'-oxindole derivatives containing five stereogenic centers in good to high yields with excellent diastereo- and enantioselectivities (see scheme). This strategy not only adds to the limited repertory of examples of asymmetric synthesis of chiral spirocyclohexaneoxindoles and octahydroacridines, but also demonstrates a one-pot consecutive synthesis with an ecological and economical protocol.

Chem. Eur. J., Mar 20, 2014, DOI: 10.1002/chem.201402002

Insights into the Organocatalyzed Synthesis of Urethanes in Supercritical Carbon Dioxide: An In Situ FTIR Spectroscopic Kinetic Study

Back to the FTIR: The most efficient organocatalysts have been identified for the reaction of alcohols with isocyanates in supercritical CO2 in a step towards a green process for polyurethane synthesis. The order of activity of the catalysts in supercritical CO2 does not always follow that observed in conventional media.

ChemCatChem, Mar 18, 2014, DOI: 10.1002/cctc.201301002

Stereoselective Metal-Free Synthesis of β-Amino Thioesters with Tertiary and Quaternary Stereogenic Centers

Thioesters on the rise: β-Amino thioesters with tertiary and even quaternary stereogenic centers can be formed with high diastereo- and enantioselectivities from Mannich reactions with monothiomalonates in the presence of catalytic amounts of cinchona alkaloids. The synthetic value of the β-amino thioesters as preactivated β-amino acids was, for example, shown in coupling-reagent-free peptide synthesis.

Angew. Chem. Int. Ed., Mar 18, 2014, DOI: 10.1002/anie.201310532

Phosphane- and Amine-Catalyzed Ring-Opening Reactions of Cyclopropenones with Isatin Derivatives: Synthesis of Carboxylated 1H-Indoles and Multisubstituted 2H-Pyran-2-ones

Phosphane- and amine-catalyzed ring-opening reactions of cyclopropenones with isatin derivatives are developed. These reactions offer a facile synthetic method to construct carboxylated 1H-indoles and multisubstituted 2H-pyran-2-ones; Boc = tert-butoxycarbonyl, DABCO = 1,4-diazabicyclo[2.2.2]octane.

Eur. J. Org. Chem., Mar 12, 2014, DOI: 10.1002/ejoc.201400077

Silvia Cauteruccio, Davide Dova, Maurizio Benaglia, Andrea Genoni, Manuel Orlandi, Emanuela Licandro
Synthesis, Characterisation, and Organocatalytic Activity of Chiral Tetrathiahelicene Diphosphine Oxides [Full Paper]

Synthesis, Characterisation, and Organocatalytic Activity of Chiral Tetrathiahelicene Diphosphine Oxides

A novel class of tetrathia[7]helicene-based diphosphine oxides has been synthesised, and their catalytic behaviour as chiral helical phosphorus Lewis bases has been preliminary investigated in organocatalytic reactions.

Eur. J. Org. Chem., Mar 06, 2014, DOI: 10.1002/ejoc.201301912

Christoph Reiter, Sònia López-Molina, Bernhard Schmid, Christian Neiss, Andreas Görling, Svetlana B. Tsogoeva
Michael Addition of N-Unprotected 2-Oxindoles to Nitrostyrene Catalyzed by Bifunctional Tertiary Amines: Crucial Role of Dispersion Interactions [Full Paper]

Michael Addition of N-Unprotected 2-Oxindoles to Nitrostyrene Catalyzed by Bifunctional Tertiary Amines: Crucial Role of Dispersion Interactions

The importance of being dispersed: Bifunctional thiourea- or sulfonamide-derived tertiary amines such as Takemoto's catalyst catalyze the enantioselective nitro-Michael addition of N-unprotected 3-substituted 2-oxindoles to nitrostyrene in high yields and enantiomeric and diastereomeric ratios. DFT calculations including van der Waals corrections are performed for the stereoisomers.

ChemCatChem, Mar 05, 2014, DOI: 10.1002/cctc.201301052

Sankaranarayanapillai Shylesh, David Hanna, Joseph Gomes, Siddarth Krishna, Christian G. Canlas, Martin Head-Gordon, Alexis T. Bell
Tailoring the Cooperative Acid–Base Effects in Silica-Supported Amine Catalysts: Applications in the Continuous Gas-Phase Self-Condensation of n-Butanal [Full Paper]

Tailoring the Cooperative Acid–Base Effects in Silica-Supported Amine Catalysts: Applications in the Continuous Gas-Phase Self-Condensation of n-Butanal

Secondary amines come first: A solid-base organocatalyst achieved by grafting amines onto silica surfaces is applied to the gas-phase aldol self-condensation of n-butanal to 2-ethylhexenal. Silica-supported secondary amine catalysts demonstrate a much higher catalytic activity than the primary amine analogues, owing to the respective formation of enamines as shown by in situ FTIR analysis. The reaction pathway is analyzed by DFT calculations.

ChemCatChem, Mar 03, 2014, DOI: 10.1002/cctc.201301087

Organocatalytic Asymmetric Friedel–Crafts Reaction of Sesamol with Isatins: Access to Biologically Relevant 3-Aryl-3-hydroxy-2-oxindoles

What a Cinch(ona)! A Cinchona alkaloid derived thiourea is successfully used to catalyze the Friedel–Crafts-type addition of sesamol to isatins to provide chiral 3-aryl-3-hydroxy-2-oxindoles in good yield with good enantioselectivity. Incorporation of a 1,2,3-triazole moiety into one oxindole derivative is performed through click chemistry to obtain a biologically important derivative with good enantiomeric excess (ee). MTBE=methyl tert-butyl ether.

Chem. Asian J., Mar 03, 2014, DOI: 10.1002/asia.201301546

Asymmetric Decarboxylative 1,4-Addition of Malonic Acid Half Thioesters to Vinyl Sulfones: Highly Enantioselective Synthesis of 3-Monofluoromethyl-3-Arylpropanoic Esters

You do the maht: The first asymmetric decarboxylative 1,4-addition of malonic acid half thioesters (MAHTs) to 2-aryl-substituted vinyl sulfones is reported. Excellent enantioselectivities (up to 97 % ee) were obtained by using a quinine-based benzyl- substituted thiourea. The highly enantioselective synthesis of 3-monofluorinated analogues of 3-methyl indanone and (+)-turmerone has been successfully accomplished.

Chem. Asian J., Mar 03, 2014, DOI: 10.1002/asia.201400049

Proline-Tetrazole-Catalyzed Enantioselective N-Nitroso Aldol Reaction of Aldehydes with In Situ Generated Nitrosocarbonyl Compounds

Sturdy as it gets: A highly enantioselective, robust, and scalable method for the synthesis of β-hydroxyamino alcohols were achieved by using the title reaction. MnO2 serves as the oxidant and catechol as Brønsted acid additive. PG=protecting group.

Angew. Chem. Int. Ed., Feb 19, 2014, DOI: 10.1002/anie.201311069

A Chiral Thioxanthone as an Organocatalyst for Enantioselective [2+2] Photocycloaddition Reactions Induced by Visible Light

Lighting up S: The thioxanthone 1, which was synthesized in a concise fashion from methyl thiosalicylate, exhibits a significant absorption in the visible-light region. It allows for an efficient enantioselective catalysis of intramolecular [2+2] photocycloaddition reactions, presumably by triplet-energy transfer. Ts=4-toluenesulfonyl.

Angew. Chem. Int. Ed. 2014, 53, No. 17, 4368-4371

Ryozo Shibuya, Lu Lin, Yasuhito Nakahara, Kazushi Mashima, Takashi Ohshima
Dual Platinum and Pyrrolidine Catalysis in the Direct Alkylation of Allylic Alcohols: Selective Synthesis of Monoallylation Products [Communication]

Dual Platinum and Pyrrolidine Catalysis in the Direct Alkylation of Allylic Alcohols: Selective Synthesis of Monoallylation Products

Two cats are better than one: The combined use of platinum and pyrrolidine catalysts enabled the direct alkylation of allylic alcohols with reactive methylene compounds. Pyrrolidine was essential for obtaining high selectivity of the monoallylation products, which were produced without the use of excess nucleophiles. cod=1,5-cyclooctadiene, EWG=electron-withdrawing group.

Angew. Chem. Int. Ed. 2014, 53, No. 17, 4377-4381

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

Kim Søholm Halskov, Bjarke S. Donslund, Sebastian Barfüsser, Karl Anker Jørgensen
Organocatalytic Asymmetric Formation of Steroids [Communication]

Organocatalytic Asymmetric Formation of Steroids

Organocatalysis made it possible: The reported methodology gives 14 β-steroids, displaying a broad generality, in one step, and includes various substituents on the A ring, variations of the B ring, hydroxy or alkyl substituents in the 12-position of the C ring, and different substituents in the angular position at C13. Furthermore, the developed reaction concept includes reactions with quinones to form D-homosteroids in excellent yields and stereoselectivities.

Angew. Chem. Int. Ed. 2014, 53, No. 16, 4137-4141

Merging Aerobic Oxidation and Enamine Catalysis in the Asymmetric α-Amination of β-Ketocarbonyls Using N-Hydroxycarbamates as Nitrogen Sources

Merging O and N: Enantioselective α-amination of β-ketocarbonyl compounds has been achieved by merging enamine catalysis and CuI-catalyzed aerobic oxidation of hydroxycarbamates. Excellent chemoselectivity and enantioselectivity are obtained with the aid of a simple primary/tertiary diamine catalyst. This presents a facile route for the asymmetric synthesis of unnatural amino acids.

Angew. Chem. Int. Ed. 2014, 53, No. 16, 4149-4153

Winnie Nzahou Ottou, Damien Bourichon, Joan Vignolle, Anne-Laure Wirotius, Fredéric Robert, Yannick Landais, Jean-Marc Sotiropoulos, Karinne Miqueu, Daniel Taton
Cyclodimerization versus Polymerization of Methyl Methacrylate Induced by N-Heterocyclic Carbenes: A Combined Experimental and Theoretical Study [Full Paper]

Cyclodimerization versus Polymerization of Methyl Methacrylate Induced by N-Heterocyclic Carbenes: A Combined Experimental and Theoretical Study

Cyclodimerizing MMA! NHCiPr (NHC=N-heterocyclic carbene) unexpectedly reacts with methyl methacrylate (MMA) by forming a stable imidazolium–enolate cyclodimer (NHCiPr/MMA=1:2), in contrast to polymerization, which is induced by NHCtBu (see scheme). DFT calculations on both mechanistic pathways highlight the differences observed between these two very similar NHCs.

Chem. Eur. J. 2014, 20, No. 14, 3989-3997

Daniel Hack, Charles C. J. Loh, Jan M. Hartmann, Gerhard Raabe, Dieter Enders
Merging Gold and Organocatalysis: A Facile Asymmetric Synthesis of Annulated Pyrroles [Communication]

Merging Gold and Organocatalysis: A Facile Asymmetric Synthesis of Annulated Pyrroles

Outwitted: The combination of cinchona-alkaloid-derived primary amine and AuI–phosphine catalysts allowed the selective C-H functionalization of two adjacent carbon atoms of pyrroles under mild reaction conditions. This sequential dual activation provides seven-membered-ring-annulated pyrrole derivatives in excellent yields and enantioselectivities (see scheme).

Chem. Eur. J. 2014, 20, No. 14, 3917-3921

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

Catalytic Enantioselective Synthesis of (S)-8-Hydroxy-3-[(S)-2'-hydroxypentyl]-6-methoxyisochroman-1-one, (S)-3-Hydroxy-3-[(S)-2'-hydroxypentyl]-6,8-dimethoxyisochroman-1-one, and Their Epimers

An iterative catalytic enantioselective asymmetric epoxidation coupled with Alder–Rickert reaction led to an efficient synthesis of (S)-8-hydroxy-3-[(S)-2'-hydroxypentyl]-6-methoxyisochroman-1-one and their stereoisomers. This method gives the option of generating diastereomers of the natural products, and it can be efficiently implemented for the synthesis of related molecules.

Eur. J. Org. Chem. 2014, No. 10, 2168-2173

Masanori Yoshida, Ami Kubara, Yuki Nagasawa, Shoji Hara, Masahiro Yamanaka
Asymmetric Michael Addition of β-Ketoesters to Enones Catalyzed by the Lithium Salt of a Primary β-Amino Acid [Full Paper]

Asymmetric Michael Addition of β-Ketoesters to Enones Catalyzed by the Lithium Salt of a Primary β-Amino Acid

A pinch of salt: A highly enantioselective Michael addition of β-ketoesters to enones was achieved by using the salt of a readily available primary β-amino acid as the catalyst. The Michael adducts were converted into enantioenriched 1,5-diketones in high yields through a common decarboxylation reaction under acidic conditions. A plausible reaction mechanism for the Michael addition reaction is also described. TBDPS=tert-butyldiphenylsilyl.

Asian J. Org. Chem. 2014, 3, No. 04, 523-529

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

Synthesis of Furanose Spirooxindoles via 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)-Catalyzed Aldol Reactions of a Pyruvic Aldehyde Derivative

Fast aldol reaction: 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) was used for aldol reactions of a pyruvic aldehyde derivative with isatins. The reactions were fast and gave the aldol products in 15–30 min at 25 °C. By using this aldol reaction method, a set of furanose spirooxindoles, which would likely be useful in the search for biofunctional molecules, were concisely synthesized.

Asian J. Org. Chem. 2014, 3, No. 04, 391-394

Feng An, Shyeni Paul, Johannes Ammer, Armin R. Ofial, Peter Mayer, Sami Lakhdar, Herbert Mayr
Structures and Reactivities of Iminium Ions Derived from Substituted Cinnamaldehydes and Various Chiral Imidazolidin-4-ones [Full Paper]

Structures and Reactivities of Iminium Ions Derived from Substituted Cinnamaldehydes and Various Chiral Imidazolidin-4-ones

Worth its salt: Iminium salts derived from substituted cinnamaldehydes and imidazolidinones have been synthesized and characterized by X-ray crystallography. Kinetic investigations of their reactions with cyclic ketene acetals were performed to quantify their electrophilic reactivity.

Asian J. Org. Chem. 2014, 3, No. 04, 550-555

Seiji Shirakawa, Kenichiro Yamamoto, Takashi Tokuda, Keiji Maruoka
Phase-Transfer-Catalyzed Asymmetric α-Arylation of α-Amino Acid Derivatives [Communication]

Phase-Transfer-Catalyzed Asymmetric α-Arylation of α-Amino Acid Derivatives

Set phasers to transfer: Highly enantioselective α-arylation of α-amino acid derivatives was achieved under phase-transfer conditions. This reaction demonstrates a valuable method for the catalytic asymmetric synthesis of α,α-disubstituted α-amino acids containing an aromatic substituent. PTC=phase-transfer catalyst; Tf=trifluoromethanesulfonyl.

Asian J. Org. Chem. 2014, 3, No. 04, 433-436

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

Rodrigo César da Silva, Indranil Chatterjee, Eduardo Escudero-Adán, Marcio Weber Paixão, Paolo Melchiorre
Synthesis of Cyclopropane Spirooxindoles by means of a Vinylogous Organocatalytic Cascade [Communication]

Synthesis of Cyclopropane Spirooxindoles by means of a Vinylogous Organocatalytic Cascade

Go with the flow: An organocatalytic vinylogous cascade reaction, which yields valuable spirooxindolic cyclopropane derivatives, is presented. This operationally simple chemistry is performed at room temperature and leads to the one-step formation of highly enantioenriched complex frameworks. The cascade follows a 1,6-addition/intramolecular SN2-alkylation sequence driven by vinylogous iminium ion/dienamine activation.

Asian J. Org. Chem. 2014, 3, No. 04, 466-469

Filip Hessler, Aleš Korotvička, David Nečas, Irena Valterová, Martin Kotora
Syntheses of a Flobufen Metabolite and Dapoxetine Based on Enantioselective Allylation of Aromatic Aldehydes [Full Paper]

Syntheses of a Flobufen Metabolite and Dapoxetine Based on Enantioselective Allylation of Aromatic Aldehydes

The enantioselective allylation of an aromatic aldehyde to give the corresponding homoallylic alcohol was the key step in the syntheses of a flobufen metabolite and dapoxetine. In the first case, the homoallylic moiety was converted into a chiral five-membered lactone ring. In the second case, it was transformed into a chiral 1,3-amino alcohol moiety.

Eur. J. Org. Chem. 2014, No. 12, 2543-2548

Sonia S. So, Anita E. Mattson
Stereoselective N-H Insertion-Arylation Reactions of Nitrodiazoesters [Communication]

Stereoselective N-H Insertion-Arylation Reactions of Nitrodiazoesters

Double the umpolung, double the fun: Chiral phosphoric acid derivatives catalyse N-H insertion/arylation reactions of nitrodiazoesters, anilines, and indoles. This process enables access to doubly α-electrophilic esters, that is, two nucleophiles undergo addition to the alpha-carbon atom of an ester. The aryl glycine products are prepared in good yield with modest levels of stereocontrol.

Asian J. Org. Chem. 2014, 3, No. 04, 425-428

Hikaru Yanai, Saki Egawa, Kenta Yamada, Junpei Ono, Motohide Aoki, Takashi Matsumoto, Takeo Taguchi
1,1-Bis(triflyl)alkadienes: Easy-To-Handle Building Blocks for Strongly Acidic Carbon Acids [Full Paper]

1,1-Bis(triflyl)alkadienes: Easy-To-Handle Building Blocks for Strongly Acidic Carbon Acids

A trifyl easy: 1,1-Bis(triflyl)alkadienes are easily available building blocks for the preparation of superacidic carbon acids that contain a bis(triflyl)methyl group. The alkadiene reactions with NaBH4 or an organocerium reagent gave the desired carbon acids through a β-selective nucleophilic addition. When submitted to a Mukaiyama aldol reaction, these β-branched carbon acids had a higher catalyst activity than that of nonbranched derivatives.

Asian J. Org. Chem. 2014, 3, No. 04, 556-563

Organocatalytic Enantio- and Diastereoselective Assembly of Thiazolidine Scaffolds by Formal [3+2] Annulation

Great balls of thia: An organocatalytic formal [3+2] annulation is described. With readily available achiral starting materials, a range of thiazolidines can be assembled in excellent yield and with moderate to good enantioselectivity and diastereoselectivity.

Asian J. Org. Chem. 2014, 3, No. 04, 387-390

Catalytic Asymmetric Alkylation of 3-Aryl-Substituted Oxindoles to give 3,3-Disubstituted Oxindoles under Phase-Transfer Conditions

Between phases: An enantioselective method for the construction of all-carbon quaternary stereocenters from 3-aryl-substituted oxindoles via asymmetric phase-transfer alkylation has been developed. The products are obtained in high yields and optical purity of up to 93 % ee by the use of (S,S)-3,4,5-trifluorophenyl-NAS bromide (I) as chiral phase-transfer catalyst. Boc=tert-butyloxycarbonyl.

Asian J. Org. Chem. 2014, 3, No. 04, 395-398

Zamani E. D. Cele, Sachin A. Pawar, Tricia Naicker, Glenn E. M. Maguire, Per I. Arvidsson, Hendrik G. Kruger, Thavendran Govender
Organocatalytic Mannich Reactions on a Carbapenem Core – Synthesis of Mannich Bases and Bicyclic Diazanonanes [Full Paper]

Organocatalytic Mannich Reactions on a Carbapenem Core – Synthesis of Mannich Bases and Bicyclic Diazanonanes

A carbapenem intermediate undergoes organocatalytic Mannich reaction with anilines to give the corresponding Mannich bases. It reacts with aliphatic or benzylic amines to give highly functionalized diazabicyclo[4.2.1]nonanes.

Eur. J. Org. Chem. 2014, No. 11, 2253-2260

Kengo Akagawa, Rieko Suzuki, Kazuaki Kudo
Development of a Peptide-Based Primary Aminocatalyst with a Helical Structure [Full Paper]

Development of a Peptide-Based Primary Aminocatalyst with a Helical Structure

A catalytic twist: A resin-supported peptide was developed for primary amine catalyzed reactions. Two tryptophan residues attached to a helix-forming sequence formed a peptide that efficiently catalyzes the asymmetric Michael addition of nitromethane to α,β-unsaturated ketones under aqueous conditions. This peptide catalyst is also applicable to other organocatalytic reactions that proceed through iminium-ion and enamine mechanisms. Aib=2-aminoisobutyric acid

Asian J. Org. Chem. 2014, 3, No. 04, 514-522

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

Ielyzaveta Bratko, Gregorio Guisado-Barrios, Isabelle Favier, Sonia Mallet-Ladeira, Emmanuelle Teuma, Eduardo Peris, Montserrat Gómez
Triazolium Salts as Appropriate Catalytic Scaffolds for 1,4-Additions to α,β-Unsaturated Carbonyls [Full Paper]

Triazolium Salts as Appropriate Catalytic Scaffolds for 1,4-Additions to α,β-Unsaturated Carbonyls

A 1,2,3-triazolium salt has been used both as an organocatalyst and as a 1,2,3-triazolylidene precursor for the preparation of a rhodium-based catalyst. The metal complex actively promotes 1,4-additions to α,β-unsaturated carbonyl compounds, and the triazolium salt was tested in the hetero-Michael addition of α,β-unsaturated ketones.

Eur. J. Org. Chem. 2014, No. 10, 2160-2167

Satoshi Okusu, Hiroyuki Kawai, Yoshimasa Yasuda, Yutaka Sugita, Takashi Kitayama, Etsuko Tokunaga, Norio Shibata
Asymmetric Synthesis of Efavirenz via Organocatalyzed Enantioselective Trifluoromethylation [Communication]

Asymmetric Synthesis of Efavirenz via Organocatalyzed Enantioselective Trifluoromethylation

No metal in mine: Anti-HIV drug efavirenz is now available by organocatalysis in 99 % ee. A combination of longer ether-type cinchona alkaloid catalysts and tetramethylammonium fluoride (TMAF) enables enantioselective trifluoromethylation of 1-(5-chloro-2-nitrophenyl)-3-cyclopropylprop-2-yn-1-one with Me3SiCF3 to provide a desired (S)-trifluoromethyl carbinol in up to 80 % ee. (S)-Trifluoromethyl carbinol is a two-step precursor for efavirenz.

Asian J. Org. Chem. 2014, 3, No. 04, 449-452

Organocatalytic Asymmetric Conjugate Addition of 2-Oxindole-3-Carboxylate Esters to 2-Phthalimido Acrylates: Efficient Synthesis of Cγ-tetrasubstituted α-Amino Acid Derivatives

A quin quin situation: An organocatalytic asymmetric conjugate addition of 2-oxindole-3-carboxylate esters to 2-phthalimidoacrylates catalyzed by a quinine-derived thiourea is described, which provides efficient access to a variety of quaternary oxindole-based Cγ-tetrasubstituted α-amino acid derivatives in up to 96 % yield and up to 90 % ee. The opposite enantiomers of the products can also be obtained by using a similar quinidine-based catalyst.

Asian J. Org. Chem. 2014, 3, No. 04, 530-535

David J. Aitken, Pierluigi Caboni, Hendrik Eijsberg, Angelo Frongia, Régis Guillot, Jean Ollivier, Pier Paolo Piras, Francesco Secci
Catalytic Enantioselective Synthesis of α-Arylaminocyclobutanones [Communication]

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

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

Xu Tian, Nora Hofmann, Paolo Melchiorre
Asymmetric Vinylogous Diels–Alder Reactions Catalyzed by a Chiral Phosphoric Acid [Communication]

Asymmetric Vinylogous Diels–Alder Reactions Catalyzed by a Chiral Phosphoric Acid

Further and further: A vinylogous Diels–Alder reaction that is catalyzed by a commercially available chiral phosphoric acid has been developed. A range of structurally diverse complex tetrahydrocarbazoles were obtained in high chemical yields and with excellent stereoselectivity. It was thus demonstrated that the synthetic utility of the Diels–Alder reaction can be extended to include a vinylogous reactivity space.

Angew. Chem. Int. Ed. 2014, 53, No. 11, 2997-3000

Francesco Manoni, Stephen J. Connon
Catalytic Asymmetric Tamura Cycloadditions [Communication]

Catalytic Asymmetric Tamura Cycloadditions

Squared away: The first strategy for bringing about enantioselective Tamura reactions is reported. In the presence of a squaramide-based catalyst, enolizable anhydrides react with alkylidene oxindoles to generate spirooxindole products with excellent enantio- and diastereocontrol. The methodology is of wide scope and leads to structurally diverse products.

Angew. Chem. Int. Ed. 2014, 53, No. 10, 2628-2632

Sylvain Koeller, Coralie Thomas, Fréderic Peruch, Alain Deffieux, Stéphane Massip, Jean-Michel Léger, Jean-Pierre Desvergne, Anne Milet, Brigitte Bibal
α-Halogenoacetanilides as Hydrogen-Bonding Organocatalysts that Activate Carbonyl Bonds: Fluorine versus Chlorine and Bromine [Full Paper]

α-Halogenoacetanilides as Hydrogen-Bonding Organocatalysts that Activate Carbonyl Bonds: Fluorine versus Chlorine and Bromine

Two are better than one or three: α-Dihalogenoacetanilides have an attractive ability to form twofold H-bonds towards C=O groups, involving a N-H···O···H-C interaction (see figure). These nonconventional O···H-CX2 H-bonds are shown to be strong by molecular modeling and solid-state packing. As organocatalysts, α-dihalogenoacetanilides allow the activation of C=O bonds in lactide, enabling full conversion into its polymer, even in the presence of a tertiary amine as cocatalyst.

Chem. Eur. J. 2014, 20, No. 10, 2849-2859

Mohammad M. Ibrahim, Dominik Grau, Frank Hampel, Svetlana B. Tsogoeva
α-Nitro Epoxides in Organic Synthesis: Development of a One-Pot Organocatalytic Strategy for the Synthesis of Quinoxalines [Full Paper]

α-Nitro Epoxides in Organic Synthesis: Development of a One-Pot Organocatalytic Strategy for the Synthesis of Quinoxalines

The reaction of easily accessible nitro olefins with the tBuOOH/1,8-diazabicycloundec-7-ene (TBHP/DBU) organocatalytic system gives rise to the corresponding α-nitro epoxides, which are suitable for subsequent reaction with 1,2-phenylenediamines under mild conditions to give quinoxaline heterocycles in up to 82 % yield.

Eur. J. Org. Chem. 2014, No. 07, 1401-1405

Synthesis of Zirconium Phosphonate Supported L-Proline as an Effective Organocatalyst for Direct Asymmetric Aldol Addition

Stable L-proline-functionalized zirconium phosphonates have been prepared and tested for the direct asymmetric aldol addition of various ketones with p-substituted benzaldehydes. High yields, diastereoselectivities and enantiomeric excesses have been obtained. Moreover, these materials can be easily recovered and used at least six times without loss of activity.

Eur. J. Org. Chem. 2014, No. 08, 1716-1726

Metal–Organocatalytic Tandem Azide Addition/Oxyamination of Aldehydes for the Enantioselective Synthesis of β-Amino α-Hydroxy Esters

The enantioselective synthesis of β-azido α-oxyaminated aldehydes is performed by iminium/enamine–iron catalysis. In this study, an azide nucleophile is first introduced to the α,β-unsaturated aldehydes in an asymmetric fashion; TEMPO = 2,2,6,6-tetramethylpiperidinyloxy.

Eur. J. Org. Chem. 2014, No. 09, 1817-1822

Ana Gradillas, Efres Belmonte, Rondes Ferreira da Silva, Javier Pérez-Castells
Hydroxy Chalcogenide-Promoted Morita–Baylis–Hillman Alkylation Reaction: Intermolecular Applications with Alkyl Halides as Electrophiles [Full Paper]

Hydroxy Chalcogenide-Promoted Morita–Baylis–Hillman Alkylation Reaction: Intermolecular Applications with Alkyl Halides as Electrophiles

Hydroxysulfides acted as catalysts to promote the Morita–Baylis–Hillman alkylation reaction of cyclohexenones and dihydropyridinones. The procedure worked efficiently with a variety of halides as electrophiles. Side reactions were in competition with the MBH alkylation, but fine-tuning the reaction conditions minimized their occurrence.

Eur. J. Org. Chem. 2014, No. 09, 1935-1941

Samydurai Jayakumar, Subramaniam Muthusamy, Muthuraj Prakash, Venkitasamy Kesavan
Enantioselective Synthesis of Spirooxindole α-exo-Methylene-γ-butyrolactones from 3-OBoc-Oxindoles [Full Paper]

Enantioselective Synthesis of Spirooxindole α-exo-Methylene-γ-butyrolactones from 3-OBoc-Oxindoles

An efficient method was developed for the synthesis of spirooxindole α-exo-methylene-γ-butyrolactone in good yield and excellent diastereoselectivity and enantioselectivity with a broad range of substrates.

Eur. J. Org. Chem. 2014, No. 09, 1893-1898

Haibin Mao, Aijun Lin, Zhongkai Tang, Hongwen Hu, Chengjian Zhu, Yixiang Cheng
Organocatalytic One-Pot Synthesis of Highly Substituted Pyridazines from Morita–Baylis–Hillman Carbonates and Diazo Compounds [Communication]

Organocatalytic One-Pot Synthesis of Highly Substituted Pyridazines from Morita–Baylis–Hillman Carbonates and Diazo Compounds

Go bio! A biologically inspired organocatalytic one-pot synthesis of highly functionalized pyridazines has been developed by starting from readily available diazo compounds and Morita–Baylis–Hillman (MBH) carbonates (see scheme; DABCO=1,4-diazobicyclo[2.2.2]octane, Boc=tert-butoxycarbonyl). Under mild reaction conditions, this synthetic route tolerated significant substrate variation to deliver a broad range of substituted products, including CF3-substituted pyridazines derivatives.

Chem. Eur. J. 2014, 20, No. 09, 2454-2458

Catalytic Asymmetric Formal [3+3] Cycloaddition of an Azomethine Ylide with 3-Indolylmethanol: Enantioselective Construction of a Six-Membered Piperidine Framework

An unusual addition: The first catalytic asymmetric formal [3+3] cycloaddition of isatin-derived 3-indolylmethanol with an in situ-generated azomethine ylide has been established to construct a chiral six-membered piperidine framework with two stereogenic centers. This approach represents the first enantioselective cycloaddition of isatin-derived 3-indolylmethanol, and it has realized an unusual enantioselective formal [3+3] cycloaddition of the azomethine ylide (DCE = 1,2-dichloroethane).

Chem. Eur. J. 2014, 20, No. 09, 2597-2604

Liher Prieto, Garazi Talavera, Uxue Uria, Efraim Reyes, Jose L. Vicario, Luisa Carrillo
Favoring Trienamine Activation through Unconjugated Dienals: Organocatalytic Enantioselective Remote Functionalization of Alkenes [Communication]

Favoring Trienamine Activation through Unconjugated Dienals: Organocatalytic Enantioselective Remote Functionalization of Alkenes

Break it up! Unconjugated 2,5-dienals appear to be more reactive substrates than the corresponding fully conjugated α,β,γ,δ-unsaturated aldehydes towards organocatalytic activation through trienamine intermediates. This reactivity has been demonstrated in the Diels–Alder reaction with nitroalkenes, a reaction that proceeds with clean β,ε-selectivity to afford the final products in high yields and stereoselectivities (see scheme; TMS=trimethylsilyl), the related polyconjugated dienals being completely unreactive.

Chem. Eur. J. 2014, 20, No. 08, 2145-2148

Hydrogenative Dearomatization of Pyridine and an Asymmetric Aza-Friedel–Crafts Alkylation Sequence

The highly efficient synthesis of enantiomerically enriched substituted piperidines in good to excellent yields and enantioselectivity has been realized by using the title reaction, which is catalyzed by the chiral phosphoric acid (CPA) (R)-1.

Angew. Chem. Int. Ed. 2014, 53, No. 08, 2194-2197

Elisabetta Massolo, Maurizio Benaglia, Rita Annunziata, Alessandro Palmieri, Giuseppe Celentano, Alessandra Forni
Stereoselective Synthesis of Functionalized Chiral 2-Nitrocyclohexanecarboxylic Esters via Catalytic Dienamine Addition to β-Substituted β-Nitroacrylates [Full Paper]

Debalina Ghosh, Jhen-Yi Lee, Chian-Yu Liu, Yen-Hsin Chiang, Hon Man Lee
Direct C-H Arylations of Unactivated Arenes Catalyzed by Amido-Functionalized Imidazolium Salts [Communication]

Andrea Gualandi, Pietro Canestrari, Enrico Emer, Pier Giorgio Cozzi
A Straightforward Organocatalytic Alkylation of 2-Arylacetaldehydes: An Approach towards Bisabolanes [Full Paper]

Young Sug Kim, Sun Min Kim, Bing Wang, Xavier Companyó, Jing Li, Albert Moyano, Seoyoung Im, Zdenek Tošner, Jung Woon Yang, Ramon Rios
Expanding the Scope of the Organocatalytic Addition of Fluorobis(phenylsulfonyl)methane to Enals: Enantioselective Cascade Synthesis of Fluoroindane and Fluorochromanol Derivatives [Full Paper]

Catalytic Asymmetric 1,2-Addition of α-Isothiocyanato Phosphonates: Synthesis of Chiral β-Hydroxy- or β-Amino-Substituted α-Amino Phosphonic Acid Derivatives

Correct chirality critical: Organocatalytic asymmetric Adol-type and Mannich-type reactions of α-isothiocyanato phosphonate have been realized. Michael addition was also applicable under the same catalytic conditions. This versatile approach provides a new route for the synthesis of diverse highly optically active functionalized α-amino phosphonic acid derivatives.

Angew. Chem. Int. Ed. 2014, 53, No. 07, 1862-1866

A General Strategy for the Catalytic, Highly Enantio- and Diastereoselective Synthesis of Indolizidine-Based Alkaloids

Organocatalysis: A unified, catalytic, and highly stereocontrolled synthesis of a broad range of indolizidine-based alkaloids has been developed that delivers the target alkaloids with high overall yields and excellent optical purity. As a key step, a very convenient three-component Brønsted acid catalyzed vinylogous Mukaiyama–Mannich reaction (VMMR) was employed (see scheme).

Chem. Eur. J. 2014, 20, No. 07, 1964-1979

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

Natália Seus, Bruna Goldani, Eder J. Lenardão, Lucielli Savegnago, Márcio W. Paixão, Diego Alves
Organocatalytic Synthesis of (Arylselanyl)phenyl-1H-1,2,3-triazole-4-carboxamides by Cycloaddition between Azidophenyl Arylselenides and β-Oxo-amides [Full Paper]

Organocatalytic Synthesis of (Arylselanyl)phenyl-1H-1,2,3-triazole-4-carboxamides by Cycloaddition between Azidophenyl Arylselenides and β-Oxo-amides

The use of β-oxo-amides in organocatalytic cycloaddition with aryl azidophenyl selenides has been developed, with the corresponding (arylselanyl)phenyl-1H-1,2,3-triazole-4-carboxamides being obtained in good to excellent yields. This organocatalytic protocol proved to be an efficient methodology for the combinatorial synthesis of new selenium-containing triazole compounds.

Eur. J. Org. Chem. 2014, No. 05, 1059-1065

Enantioselective Squaramide-Catalysed Domino Mannich–Cyclization Reaction of Isatin Imines

An enantioselective domino reaction was developed to construct 3-amino-2-oxindoles. With 1 mol-% of a bifunctional squaramide organocatalyst, the desired products were achieved in high yields and with excellent enantioselectivities.

Eur. J. Org. Chem. 2014, No. 04, 739-744

Organocatalyzed Highly Diastereo- and Enantioselective Tandem Sulfa-Michael–Mannich Reaction of 2-Mercaptoquinoline-3-carbaldimines with Maleimides

Four rings, three stereocenters: The asymmetric cascade sulfa-Michael–Mannich reaction of 2-mercapto-quinoline-3-carbaldimines with maleimides catalyzed by a bifunctional tertiary amine–thiourea affords tetracyclic quinoline derivatives with three contiguous stereocenters in high yield with excellent diastereo- (>99:1 dr) and enantioselectivities (90–>99 % ee).

ChemCatChem 2014, 6, No. 02, 649-654

Carbocations as Lewis Acid Catalysts in Diels–Alder and Michael Addition Reactions

The quest for the forgotten Lewis acid: A potential Lewis acid catalyst that has received negligible attention is the carbocation. The ability of the triphenylmethyl (trityl) carbocation as a powerful catalyst for the Diels–Alder reaction is demonstrated for a range of substrates. Low catalyst loadings, excellent yields, and good endo/exo selectivities were achieved (see scheme).

Chem. Eur. J. 2014, 20, No. 04, 1066-1072

Stereocontrol of All-Carbon Quaternary Centers through Enantioselective Desymmetrization of Meso Primary Diols by Organocatalyzed Acyl Transfer

Smashing the mirror: The symmetry breaking of meso primary diols was employed to control all-carbon quaternary stereocenters using catalytic asymmetric acyl transfer. The planar chiral Fu DMAP catalyst was used to reach a high degree of enantioselectivity (up to 97:3 e.r.) through a synergic effect, combining a desymmetrization step and a kinetic resolution.

Angew. Chem. Int. Ed. 2014, 53, No. 03, 766-770

Rebecca L. Davis, Kim L. Jensen, Björn Gschwend, Karl Anker Jørgensen
On the Mechanism of the Organocatalytic Asymmetric Epoxidation of α,β-Unsaturated Aldehydes [Communication]

On the Mechanism of the Organocatalytic Asymmetric Epoxidation of α,β-Unsaturated Aldehydes

Self-promotion: Mechanistic studies on the organocatalytic epoxidation of α,β-unsaturated aldehydes reveal the autoinductive behavior and establish that the hydrate/peroxyhydrate of the product is acting as a phase-transfer catalyst. Based on these results, an improved methodology that provides high selectivities and decreased catalyst loading, through the addition of chloral hydrate, has been developed (see scheme).

Chem. Eur. J. 2014, 20, No. 01, 64-67

Zhengnian Li, Lijuan Zhang, Fayang G. Qiu
A Concise Stereocontrolled Total Synthesis of (±)-Stemoamide [Communication]

A Concise Stereocontrolled Total Synthesis of (±)-Stemoamide

Hit for six: (±)-Stemoamide was synthesized in six steps starting from readily accessible 2-trimethylsilioxy-3-methylfuran, methyl-4-nitrobutyrate, and acrolein after converting the nitro group into a ketone and a subsequent reductive amination.

Asian J. Org. Chem. 2014, 3, No. 01, 52-54

Direct α-Vinylidenation of Aldehydes and Subsequent Cascade: Gold and Amine Catalysts Work Synergistically

Gold and amine team up: Gold and an amine catalyst work synergistically to promote either an α-vinylidenation or an α-vinylidenation/γ-functionalization of aldehydes to generate tri- and tetrasubstituted allenes. The allene products also undergo an additional reaction to generate polysubstituted furans.

Angew. Chem. Int. Ed. 2013, 52, No. 52, 14219-14223

Kinetic Resolution of Axially Chiral 2-Amino-1,1'-Biaryls by Phase-Transfer-Catalyzed N-Allylation

Going through a phase: The highly selective kinetic resolution of the title compounds, which are important chiral building blocks, was achieved by phase-transfer-catalyzed N-allylation. This synthetic method was applied to the highly enantioselective desymmetrization of a biaryl compound.

Angew. Chem. Int. Ed. 2013, 52, No. 52, 14200-14203

Maria del Mar Sanchez Duque, Olivier Baslé, Yves Génisson, Jean-Christophe Plaquevent, Xavier Bugaut, Thierry Constantieux, Jean Rodriguez
Enantioselective Organocatalytic Multicomponent Synthesis of 2,6-Diazabicyclo[2.2.2]octanones [Communication]

Enantioselective Organocatalytic Multicomponent Synthesis of 2,6-Diazabicyclo[2.2.2]octanones

Three-star compounds: The title reaction of β-ketoamides, acrolein, and aminophenols, catalyzed by a bifunctional thiourea-tertiary amine organocatalyst, enables the preparation of an enantioenriched diazabicyclo[2.2.2]octanone (2,6-DABCO) scaffold. The chemoselective reaction sequence installs five new bonds and three stereocenters, two of which are contiguous tetrasubstituted centers, with excellent yields and high levels of stereocontrol. M.S.=molecular sieves.

Angew. Chem. Int. Ed. 2013, 52, No. 52, 14143-14146

Takasuke Mukaiyama , Hayato Ishikawa , Hiroyuki Koshino, Yujiro Hayashi 
One-Pot Synthesis of (−)-Oseltamivir and Mechanistic Insights into the Organocatalyzed Michael Reaction [Full Paper]

One-Pot Synthesis of (−)-Oseltamivir and Mechanistic Insights into the Organocatalyzed Michael Reaction

(−)-Oseltamivir, a neuraminidase inhibitor, was synthesized in a one-pot operation (see scheme). A mechanistic study of the key Michael reaction revealed that both E and Z enamines are generated, acid accelerates EZ enamine isomerization, and reactivity depends on the geometry of both Michael acceptor and enamine.

Chem. Eur. J. 2013, 19, No. 52, 17789-17800

Conjugate-Base-Stabilized Brønsted Acids as Asymmetric Catalysts: Enantioselective Povarov Reactions with Secondary Aromatic Amines

Caught in the act: A new concept for asymmetric Brønsted acid catalysis is presented. Compounds containing an acidic functionality in addition to an anion recognition site act as powerful conjugate-base-stabilized Brønsted acid catalysts. This strategy was applied to the first catalytic enantioselective three-component Povarov reaction of indoline and other secondary aromatic amines (see scheme; M.S.=molecular sieves).

Angew. Chem. Int. Ed. 2013, 52, No. 52, 14084-14088

Weijun Yang, Zhigen Yang, Lijun Xu, Lili Zhang, Xin Xu, Maozhong Miao, Hongjun Ren
Surfactant-Type Brønsted Acid Catalyzed Stereoselective Synthesis of trans-3-Alkenyl Indazoles from Triazenylaryl Allylic Alcohols in Water [Communication]

Surfactant-Type Brønsted Acid Catalyzed Stereoselective Synthesis of trans-3-Alkenyl Indazoles from Triazenylaryl Allylic Alcohols in Water

Testing the waters: An efficient dodecyl benzene sulfonic acid (DBSA) catalyzed approach to the synthesis of the title compounds in water is reported. Furthermore, upon cleavage of the pyrrolidine group from the trans-3-alkenyl-2-pyrrolidine-2H-indazoles with Zn in CH3COOH, trans-3-alkenyl-1H-indazoles are obtained in good to excellent yields.

Angew. Chem. Int. Ed. 2013, 52, No. 52, 14135-14139

Trienamines Derived from Interrupted Cyclic 2,5-Dienones: Remote δ,ε-C=C Bond Activation for Asymmetric Inverse-Electron-Demand Aza-Diels–Alder Reaction

Newly framed: The δ,ε C=C bond of an interrupted cyclic 2,5-dienone induces the formation of a linear trienamine in the presence of a chiral primary amine, thus enabling the δ,ε-C=C bond to participate in a highly asymmetric inverse-electron-demand aza-Diels–Alder (DA) reaction with electron-deficient 1-azadienes. The DA reaction can be coupled with a Michael addition to produce a polycyclic framework with complete stereocontrol.

Angew. Chem. Int. Ed. 2013, 52, No. 52, 14173-14176

Alejandro Parra, Silvia Reboredo
Chiral Hypervalent Iodine Reagents: Synthesis and Reactivity [Minireview]

Chiral Hypervalent Iodine Reagents: Synthesis and Reactivity

All about iodine: Chiral hypervalent iodine chemistry has been steadily increasing in importance in recent years. This Minieview catalogues enantioselective transformations triggered by chiral hypervalent iodine(III/V) reagents, in stoichiometric or catalytic quantities, highlighting the different reactivities in terms of yield and enantioselectivity. Moreover, the synthesis of the most remarkable and successful catalysts has been illustrated in detail.

Chem. Eur. J. 2013, 19, No. 51, 17244-17260

Elizabeth O'Bryan McCusker, Karl A. Scheidt
Enantioselective N-Heterocyclic Carbene Catalyzed Annulation Reactions with Imidazolidinones [Communication]

Enantioselective N-Heterocyclic Carbene Catalyzed Annulation Reactions with Imidazolidinones

Add acetic acid: A highly stereoselective N-heterocyclic carbene (NHC)-catalyzed formal [4+2] annulation between α,β-unsaturated aldehydes and imidazolidinones for the synthesis of imidazoles has been developed. Acetic acid serves as a key additive to achieve high chemoselectivity for the formal [4+2] annulation product.

Angew. Chem. Int. Ed. 2013, 52, No. 51, 13616-13620

Qijian Ni, Huan Zhang, André Grossmann, Charles C. J. Loh, Carina Merkens, Dieter Enders
Asymmetric Synthesis of Pyrroloindolones by N-Heterocyclic Carbene Catalyzed [2+3] Annulation of α-Chloroaldehydes with Nitrovinylindoles [Communication]

Asymmetric Synthesis of Pyrroloindolones by N-Heterocyclic Carbene Catalyzed [2+3] Annulation of α-Chloroaldehydes with Nitrovinylindoles

NHC-enolate plus 3: N-heterocyclic carbenes (NHCs) serve as organocatalysts for the [2+3] annulation of nitrovinylindoles with α-chloroaldehydes via an intermediate azolium enolate. The method provides trans-disubstituted pyrroloindolones with good yields and excellent diastereo- and enantioselectivities. Further transformations lead to tetracyclic pyrrolo[1,2-a]indoles with potential psychotropic and other bioactivities.

Angew. Chem. Int. Ed. 2013, 52, No. 51, 13562-13566

Yun-Lin Liu, Xin Wang, Yu-Lei Zhao, Feng Zhu, Xing-Ping Zeng, Long Chen, Cui-Hong Wang, Xiao-Li Zhao, Jian Zhou
One-Pot Tandem Approach to Spirocyclic Oxindoles Featuring Adjacent Spiro-Stereocenters [Communication]

One-Pot Tandem Approach to Spirocyclic Oxindoles Featuring Adjacent Spiro-Stereocenters

All in a sequence: An organocatalyzed Morita–Baylis–Hillman (MBH)/bromination/[3+2] annulation sequence for highly stereoselective syntheses of bis(spirooxindole)s featuring adjacent spiro-stereocenters is described. The key step is an unprecedented catalytic asymmetric [3+2] annulation of isatin-derived MBH adducts, containing a tetrasubstituted alkene moiety, with isatins.

Angew. Chem. Int. Ed. 2013, 52, No. 51, 13735-13739

Enantio- and Diastereoselective Assembly of Tetrahydrofuran and Tetrahydropyran Skeletons with All-Carbon-Substituted Quaternary Stereocenters

Chiral phosphoric acids (HB*) catalyze the asymmetric desymmetrization of meso 1,3-diols through mono-transacetalization with a tethered acetal unit (see scheme). This new strategy leads to the efficient assembly of tetrahydrofuran and tetrahydropyran skeletons bearing remote all-carbon-substituted quaternary stereocenters that are not straightforward to access by other methods.

Angew. Chem. Int. Ed. 2013, 52, No. 51, 13593-13596

Direct Catalytic Asymmetric Synthesis of N-Heterocycles from Commodity Acid Chlorides by Employing α,β-Unsaturated Acylammonium Salts

Taming the beast, asymmetrically: Modulation of the reactivity of acid chlorides, using cinchona alkaloid catalysts, results in chiral α,β-unsaturated acylammoniums, which react with nucleophiles enantioselectively to give pyrrolidinones, piperid-2-ones, and dihydropyridinones. This nucleophile-catalyzed Michael/proton transfer/lactamization or lactonization organocascade leads to chiral intermediates previously employed for the synthesis of bioactive pharmaceuticals.

Angew. Chem. Int. Ed. 2013, 52, No. 51, 13688-13693

Feng Shi, Wei Tan, Hong-Hao Zhang, Mei Li, Qin Ye, Guan-Hua Ma, Shu-Jiang Tu, Guigen Li
Asymmetric Organocatalytic Tandem Cyclization/Transfer Hydrogenation: A Synthetic Strategy for Enantioenriched Nitrogen Heterocycles [Update]

Yong Sup Lee, Md. Maqusood Alam, Rangappa S Keri
Enantioselective Reactions of N-Acyliminium Ions Using Chiral Organocatalysts [Focus Review]

Enantioselective Reactions of N-Acyliminium Ions Using Chiral Organocatalysts

Smells like team spirit: N-acylimium ions are important reactive intermediates for the enantioselective synthesis of nitrogen-containing compounds. This review summarizes the enantioselective reactions of N-acyliminium ions with two different chiral organocatalysts, thioureas (A) and BINOL-derived phosphoric acid derivatives (B).

Chem. Asian J. 2013, 8, No. 12, 2906-2919

Martin J. Lear, Yujiro Hayashi
Remote 1,6-Stereocontrol by Iminium-mediated Organocatalytic Events [Highlight]

Remote 1,6-Stereocontrol by Iminium-mediated Organocatalytic Events

Control freaks: Chiral amine catalysts prove to be highly proficient mediators in the asymmetric, polyconjugate addition of C-, N-, and S-based nucleophiles to acyclic dienals and cyclic dienones. For high 1,6-selectivities, the stereo spatial matching of the molecular orbitals and ionic charges of the reacting species are key. But can we widen the scope and how far can we go with remote, iminium-stereocontrol?

ChemCatChem 2013, 5, No. 12, 3499-3501

Organocatalytic Asymmetric Conjugate Addition of Aldehydes to Nitroolefins: Identification of Catalytic Intermediates and the Stereoselectivity-Determining Step by ESI-MS

Looking back: The asymmetric organocatalytic 1,4-addition of aldehydes to nitroolefins was studied by ESI-MS. Analysis of the back reaction starting from quasienantiomeric mass-labeled 1,4-adducts (see scheme) provided conclusive evidence for an enamine rather than an enol mechanism, and allowed identification of the enantioselectivity-determining step.

Angew. Chem. Int. Ed. 2013, 52, No. 48, 12619-12623

Catalytic Enantioselective Michael Addition of α-Aryl-α-Isocyanoacetates to Vinyl Selenone: Synthesis of α,α-Disubstituted α-Amino Acids and (+)- and (−)-Trigonoliimine A

Be like Mike: The title reaction in the presence of the catalyst 1 afforded Michael adducts in excellent yields and enantioselectivities. The adducts were readily converted into α,α'-disubstituted α-amino acids. The enantioselective total synthesis of both (+)- and (−)-trigonoliimine A was accomplished using one of the Michael adducts derived from this methodology. M.S.=molecular sieves.

Angew. Chem. Int. Ed. 2013, 52, No. 48, 12714-12718

Bis(amino)cyclopropenylidenes as Organocatalysts for Acyl Anion and Extended Umpolung Reactions

Back to BACs: In the pursuit of novel carbene organocatalysts, bis(amino)cyclopropenylidenes (BACs) were explored as alternatives to N-heterocyclic carbenes. They were effective in catalyzing the Stetter reaction, and displayed unique advantages over the commonly used thiazolylidenes and triazolylidenes. They also mediated extended umpolung reactions of enals. In addition, chiral analogues can be accessed readily for applications in enantioselective catalysis.

Angew. Chem. Int. Ed. 2013, 52, No. 48, 12651-12654

Yusuke Sasano, Keiichi Murakami, Tomohiro Nishiyama, Eunsang Kwon, Yoshiharu Iwabuchi
3-Methyl-4-oxa-5-azahomoadamantane: Alkoxyamine-Type Organocatalyst for Alcohol Oxidation [Communication]

3-Methyl-4-oxa-5-azahomoadamantane: Alkoxyamine-Type Organocatalyst for Alcohol Oxidation

Strong, silent type: A novel alkoxyamine-type organocatalyst has been discovered for alcohol oxidation (see scheme). The alkoxyamine exhibits a high catalytic activity for the oxidation of alcohols to afford the corresponding carbonyl compounds in high yield by oxidative transformation into an oxoammonium ion, which is proposed to serve as an active species.

Angew. Chem. Int. Ed. 2013, 52, No. 48, 12624-12627

Katherine R. Law, Christopher S. P. McErlean
Extending the Stetter Reaction with 1,6-Acceptors [Communication]

Extending the Stetter Reaction with 1,6-Acceptors

Pace Stetter: A new N-heterocyclic carbene (NHC)-catalysed transformation is described—the intramolecular vinylogous Stetter reaction. This transformation can be effected with both thiazolium and triazolium-based catalysts, using aromatic and aliphatic aldehydes, employing α,β,γ,δ-unsaturated esters, ketones, phosphonates and N-acylpyrroles, and can be conducted enantioselectively (see scheme).

Chem. Eur. J. 2013, 19, No. 47, 15852-15855

Enantioselective Sulfonation of Enones with Sulfonyl Imines by Cooperative N-Heterocyclic-Carbene/Thiourea/Tertiary-Amine Multicatalysis

Many hands make light work: In an organocatalytic asymmetric sulfonation of enones, the activation of a sulfonyl imine by an N-heterocyclic carbene (NHC) catalyst led to the release of a sulfinic anion, which underwent nucleophilic addition to the enone. The enantioselectivity of the process was controlled by a chiral thiourea/amine co-catalyst through anion recognition and hydrogen-bonding interactions. Tol=p-tolyl.

Angew. Chem. Int. Ed. 2013, 52, No. 47, 12354-12358

Tomoya Kimura, Maiko Sekine, Daisuke Takahashi, Kazunobu Toshima
Chiral Brønsted Acid Mediated Glycosylation with Recognition of Alcohol Chirality [Communication]

Chiral Brønsted Acid Mediated Glycosylation with Recognition of Alcohol Chirality

Sugar sugar: In the glycosylation of racemic alcohols with 1 using the chiral phosphoric acid 2 as an activator, one enantiomer of the racemic alcohol selectively reacts with 1 to give the corresponding glycoside with good to excellent α/β-stereo- and diastereoselectivity in high yield. The reaction was successfully applied to the synthesis of a chiral natural flavan glycoside using a racemic aglycon.

Angew. Chem. Int. Ed. 2013, 52, No. 46, 12131-12134

Han Yong Bae, Jae Hun Sim, Ji-Woong Lee, Benjamin List, Choong Eui Song
Organocatalytic Enantioselective Decarboxylative Aldol Reaction of Malonic Acid Half Thioesters with Aldehydes [Communication]

Organocatalytic Enantioselective Decarboxylative Aldol Reaction of Malonic Acid Half Thioesters with Aldehydes

Copycat: A highly enantioselective biomimetic aldol reaction of malonic acid half thioesters with a variety of aldehydes affords optically active β-hydroxy thioesters by employing the cinchona-derived sulfonamide organocatalyst 1. The synthetic utility of this protocol was demonstrated by performing formal syntheses of the antidepressants (R)-fluoxetine, (R)-tomoxetine, (−)-paroxetine, and (R)-duloxetine.

Angew. Chem. Int. Ed. 2013, 52, No. 46, 12143-12147

Origin of the Superior Performance of (Thio)Squaramides over (Thio)Ureas in Organocatalysis

Bifunctional catalysts: The performance of (thio)squaramide and (thio)urea-derived aminocatalysts was probed computationally within the context of Diels–Alder cycloadditions of nitrostyrene and anthracene (see figure). A proposed thiosquaramide-based catalyst is predicted to give the lowest reaction barrier, which stems from the ability of thiosquaramides to engage in stronger hydrogen-bonding interactions.

Chem. Eur. J. 2013, 19, No. 45, 15141-15147

Christopher J. O'Brien, Zachary S. Nixon, Andrew J. Holohan, Stephen R. Kunkel, Jennifer L. Tellez, Bryan J. Doonan, Emma E. Coyle, Florie Lavigne, Lauren J. Kang, Katherine C. Przeworski
Part I: The Development of the Catalytic Wittig Reaction [Full Paper]

Part I: The Development of the Catalytic Wittig Reaction

A point of difference: By utilizing an organosilane to chemoselectively reduce a phosphane oxide precatalyst to a phosphane (see scheme), the first catalytic (in phosphane) Wittig reaction has been developed. The methodology has been applied to the synthesis of 22 disubstituted and 24 trisubstituted olefins, including a multigram synthesis of a precursor to the anti-Alzheimer drug donepezil hydrochloride.

Chem. Eur. J. 2013, 19, No. 45, 15281-15289

Wuming Yan, Xiaodong Shi, Cheng Zhong
Secondary Amines as Lewis Bases in Nitroalkene Activation [Focus Review]

Secondary Amines as Lewis Bases in Nitroalkene Activation

Second to none: Secondary amines are well-known enamine and iminium catalysts that can also be used as Lewis bases for the activation of electron-deficient olefins. In this Focus Review, a series of systematic studies on activation of nitroolefins with secondary amines as Lewis bases that give different multicomponent condensation products are described. Asymmetric syntheses of heterocycles based on this strategy are also presented.

Asian J. Org. Chem. 2013, 2, No. 11, 904-914

Recent Advances in Organocatalytic Methods for Asymmetric C-C Bond Formation

A large number of organocatalytic processes are already well established in organic synthesis. Nevertheless, the number of publications in this field is still on the increase; new important results are produced constantly. This review gives a detailed overview of the latest developments and main streams in organocatalyzed asymmetric C-C bond formation of the last three years. It is intended to outline the most important current findings focused on especially new synthetic methodologies.

Chem. Eur. J. 2013, 19, No. 43, 14346-14396

Senthil Narayanaperumal, Daniel G. Rivera, Rodrigo C. Silva, Márcio W. Paixão
Terpene-Derived Bifunctional Thioureas in Asymmetric Organocatalysis [Review]

Terpene-Derived Bifunctional Thioureas in Asymmetric Organocatalysis

From pine resin to catalyst: The easily available rosin diterpene abietic acid has been transformed into a unique class of bifunctional thiourea catalysts that can also incorporate further substituents, thereby enabling either Lewis base or enamine activation modes. Their application in a wide range of stereoselective transformations has revealed the positive effect of this chiral and rigid skeleton on the catalytic performance of these hybrid thioureas.

ChemCatChem 2013, 5, No. 10, 2756-2773

Kazutaka Shibatomi, Akira Narayama
Catalytic Enantioselective α-Chlorination of Carbonyl Compounds [Focus Review]

Catalytic Enantioselective α-Chlorination of Carbonyl Compounds

Being the alpha: Despite the synthetic utility of chiral alkyl chlorides, catalytic methods for achieving enantioselective chlorination were only developed a decade ago. This Focus Review discusses the catalytic enantioselective α-chlorination of carbonyl compounds, as well as some stereospecific substitution reactions of the resulting optically active chlorides.

Asian J. Org. Chem. 2013, 2, No. 10, 812-823

Simple Organic Molecules as Catalysts for the Enantioselective Synthesis of Amines and Alcohols

Valiant catalysis: Hoveyda et al. have developed a set of catalysts derived from valine for enantioselective syntheses. Reagents are inexpensive, allyl additions are scalable, harsh conditions are avoided, and reactions can be performed with 0.25 mol % catalyst in under 6 h at room temperature. The efficiency, economy, selectivity, and simplicity of the transformations and the range of boron reagents look to have sustained impact on future progress in amine and alcohol syntheses.

ChemCatChem 2013, 5, No. 10, 2805-2808

Recent Advances in the Use of Chiral Brønsted Acids as Cooperative Catalysts in Cascade and Multicomponent Reactions

When one catalyst meets another: Since chiral Brønsted acids catalysts were discovered more than a decade ago, they have become prevalent in organocatalysis. Researchers have recently used cooperative catalysis to improve existing transformations and discover new reactions. This Focus Review summarizes the achievements made in the field of asymmetric cascade/multicomponent reactions with the help of cooperative catalysis from chiral Brønsted acids.

Asian J. Org. Chem. 2013, 2, No. 10, 824-836

Powerful Amino Acid Derived Bifunctional Phosphine Catalysts Bearing a Hydrogen Bond Donor in Asymmetric Synthesis

Phosphines and hydrogen bonding are good collaborators! Air-stable α-amino acids or dipeptide derived chiral phosphines bearing hydrogen-bond-donating and silicon-based bulky groups are powerful and versatile catalysts for a range of enantioselective processes, including [3+2] and [4+2] cycloadditions, allylic alkylations, Morita–Baylis–Hillman reactions, and Michael addition reactions. They represent a class of novel, economical, and practical chiral phosphine-based organocatalysts.

ChemCatChem 2013, 5, No. 10, 2775-2784

Pedro O. Miranda, Patricia Llanes, Laleh Torkian, Miquel A. Pericàs
A Fluorous Proline Organocatalyst with Acetone-Dependent Aldolase Behavior [Short Communication]

A Fluorous Proline Organocatalyst with Acetone-Dependent Aldolase Behavior

An unusual specificity for acetone as the nucleophile is observed in asymmetric cross-aldol reactions with aldehydes catalyzed by a fluorous proline derivative. The reactions take place in acetone/perfluorohexane under biphasic conditions, and the valuable catalyst/perfluorohexane phase can be repeatedly recycled.

Eur. J. Org. Chem. 2013, No. 28, 6254-6258

Organocatalytic Asymmetric Allylic Alkylation of Morita–Baylis–Hillman Carbonates with Phosphorus Ylides: Synthesis of Chiral 3-Substituted 2,4-Functionalized 1,4-Pentadienes

A highly efficient asymmetric allylic alkylation reaction of Morita–Baylis–Hillman carbonates with phosphorus ylides under the catalysis of modified cinchona alkaloids is described. Chiral 3-substituted 2,4-functionalized 1,4-pentadienes can be obtained with excellent enantioselectivities (up to 98 % ee) under mild reaction conditions. Boc = tert-butoxycarbonyl.

Eur. J. Org. Chem. 2013, No. 28, 6241-6245

PCy3-Catalyzed Ring Expansion of Aziridinofullerenes with CO2 and Aryl Isocyanates: Evidence for a Two Consecutive Nucleophilic Substitution Pathway on the Fullerene Cage

New balls please: A PCy3-catalyzed ring-expansion reaction of aziridine-fused fullerenes (aziridinofullerenes) by the insertion of CO2 and aryl isocyanates is disclosed (see scheme). This allows for CO2 fixation by aziridinofullerenes. The expansion with aryl isocyanates led to a new fullerene family, imidazolidinone-fused fullerenes, in high yields. A mechanistically related unprecedented fullerenyl phosphonium salt was also successfully isolated (Cy=cyclohexyl).

Chem. Eur. J. 2013, 19, No. 40, 13479-13483

Christina Lohoelter, Magdalena Weckbecker, Siegfried R. Waldvogel
(–)-Isosteviol as a Versatile Ex-Chiral-Pool Building Block for Organic Chemistry [Microreview]

(–)-Isosteviol as a Versatile Ex-Chiral-Pool Building Block for Organic Chemistry

The inexpensive and readily available ex-chiral-pool building block (–)-isosteviol provides unique geometric features such as the rigid and concave arrangement of its functional groups. Consequently, this valuable architecture has found significant applications in various fields of organic chemistry.

Eur. J. Org. Chem. 2013, No. 25, 5539-5554

Nicola Kielland, Christopher J. Whiteoak, Arjan W. Kleij
Stereoselective Synthesis with Carbon Dioxide [Review]

Somayeh Mohammadi, Roghayeh Heiran, Raquel P. Herrera, Eugenia Marqués-López
Isatin as a Strategic Motif for Asymmetric Catalysis [Minireview]

Isatin as a Strategic Motif for Asymmetric Catalysis

Strategic move: Isatin as a core structure has inspired the development of useful catalytic strategies to give access to interesting molecular architectures with biological activity.

ChemCatChem 2013, 5, No. 08, 2131-2148

Morgan Hans, Johan Wouters, Albert Demonceau, Lionel Delaude
Mechanistic Insight into the Staudinger Reaction Catalyzed by N-Heterocyclic Carbenes [Full Paper]

Mechanistic Insight into the Staudinger Reaction Catalyzed by N-Heterocyclic Carbenes

Catalysts caught in the act: The N-heterocyclic carbenes 1,3-dimesitylimidazolin-2-ylidene (SIMes) and 1,3-dimesitylimidazol-2-ylidene (IMes) react with N-tosyl benzaldimine or diphenylketene to afford the corresponding zwitterions in high yields (see scheme). The molecular structures of three of them were determined by X-ray crystallography and their thermal stability was monitored by thermogravimetric analysis. The NHC·ketene betaines were found to be key intermediates for the Staudinger reaction catalyzed by NHCs.

Chem. Eur. J. 2013, 19, No. 29, 9668-9676

Yuan Yao, Jun-Long Li, Qing-Qing Zhou, Lin Dong, Ying-Chun Chen
Enantioselective Aza-Morita–Baylis–Hillman Reaction with Ketimines and Acrolein Catalyzed by Organic Assemblies [Communication]

Enantioselective Aza-Morita–Baylis–Hillman Reaction with Ketimines and Acrolein Catalyzed by Organic Assemblies

Some assembly required: The first enantioselective aza-Morita–Baylis–Hillman (MBH) reaction with imines of β,γ-unsaturated α-ketoesters and acrolein was developed. The transformation is catalyzed by a combined system of β-ICD and (R)-BINOL (1) or a bifunctional tertiary amine–thiourea 2. Experimental results and preliminary spectroscopy studies demonstrated that self-assembly between β-ICD and the additive may occur, which then promotes the asymmetric aza-MBH reaction through a synergistic activation mode.

Chem. Eur. J. 2013, 19, No. 29, 9447-9451

Primary–Tertiary Diamine/Brønsted Acid Catalyzed C–C Coupling between para-Vinylanilines and Aldehydes

Aromatic enamines: para-Vinylanilines were identified as unique nucleophiles, closely resembling enamines, to undergo C-C coupling with aldehydes catalyzed by a simple primary–tertiary diamine/Brønsted acid. The resulting bis(allylic) adducts, which have potential as functional materials, were obtained in high yields under rather mild conditions (see scheme).

Chem. Eur. J. 2013, 19, No. 29, 9481-9484

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]

Organocatalysis by Neutral Multidentate Halogen-Bond Donors

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. 2013, 52, No. 27, 7028-7032

Recent Developments in Amine-catalyzed Non-asymmetric Transformations

Ready, amine, fire! Amine catalysis is a useful and well-studied method for constructing a wide variety of chiral scaffolds in asymmetric synthesis. However, organocatalysis with amines that is not centered on asymmetric transformations is also developing at a rapid rate. In this Focus Review, reports on amine catalyzed non-asymmetric transformations are examined.

Asian J. Org. Chem. 2013, 2, No. 07, 542-557

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]

Investigation of the Carboxylate Position during the Acylation Reaction Catalyzed by Biaryl DMAP Derivatives with an Internal Carboxylate

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. 2013, 52, No. 25, 6445-6449

Gloria Rassu, Vincenzo Zambrano, Luigi Pinna, Claudio Curti, Lucia Battistini, Andrea Sartori, Giorgio Pelosi, Franca Zanardi, Giovanni Casiraghi
Direct Regio-, Diastereo-, and Enantioselective Vinylogous Michael Addition of Prochiral 3-Alkylideneoxindoles to Nitroolefins [Update]

Catherine Gomez, Jean-François Betzer, Arnaud Voituriez, Angela Marinetti
Phosphine Organocatalysis in the Synthesis of Natural Products and Bioactive Compounds [Minireview]

Phosphine Organocatalysis in the Synthesis of Natural Products and Bioactive Compounds

From all natural to bioactive: This review shows that organocatalytic methods based on the use of nucleophilic phosphorus catalysts have been successfully applied as key steps in the formal or total synthesis of complex natural products. These methods also afford suitable tools for the constitution of either focused or diversity-oriented-synthesis inspired libraries of small molecules for biological screening.

ChemCatChem 2013, 5, No. 05, 1055-1065

Organocatalyzed Carbonyl–Olefin Metathesis

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.

Angew. Chem. Int. Ed. 2013, 52, No. 17, 4524-4525

Seiji Shirakawa, Keiji Maruoka
Recent Developments in Asymmetric Phase-Transfer Reactions [Review]

Recent Developments in Asymmetric Phase-Transfer Reactions

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.

Angew. Chem. Int. Ed. 2013, 52, No. 16, 4312-4348

Suman De Sarkar, Anup Biswas, Ramesh C. Samanta, Armido Studer
Catalysis with N-Heterocyclic Carbenes under Oxidative Conditions [Concept]

Catalysis with N-Heterocyclic Carbenes under Oxidative Conditions

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.

Chem. Eur. J. 2013, 19, No. 15, 4664-4678

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]

Rafael Gramage-Doria, Joost N. H. Reek
Organocatalysis in Confined Spaces [Highlight]

Organocatalysis in Confined Spaces

Strap in with organocatalysis: Organocatalysis can often give rise to unprecedented selectivities by encapsulation of the catalytic active site in an analogous manner as enzymes. Catalyst encapsulation can be considered as a powerful strategy for achieving unique transformations in a very efficient way.

ChemCatChem 2013, 5, No. 03, 677-679

Mechanism of Diphenylprolinol Silyl Ether Catalyzed Michael Addition Revisited—but Still Controversial

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).

Angew. Chem. Int. Ed. 2013, 52, No. 08, 2160-2162

Gonzalo de Gonzalo, Marco W. Fraaije
Recent Developments in Flavin-based Catalysis [Minireview]

Recent Developments in Flavin-based Catalysis

What to do with vitamin B2: Flavins are ubiquitous cofactors for enzymes and have been explored extensively as organocatalysts. Recent developments in the synthesis and use of flavin derivatives are discussed in this Minireview.

ChemCatChem 2013, 5, No. 02, 403-415

Asymmetric Organocatalytic Addition Reactions of Maleimides: A Promising Approach Towards the Synthesis of Chiral Succinimide Derivatives

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.

Chem. Asian J. 2013, 8, No. 02, 328-346

Asymmetric Counteranion-Directed Catalysis: Concept, Definition, and Applications

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.

Angew. Chem. Int. Ed. 2013, 52, No. 02, 518-533

© Wiley-VCH 2013.