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The term organocatalysis describes the acceleration of chemical reactions through the addition of a substoichiometric quantity of an organic compound. The interest in this field has increased spectacularly in the last few years as result of both the novelty of the concept and, more importantly, the fact that the efficiency and selectivity of many organocatalytic reactions meet the standards of established organic reactions. Organocatalytic reactions are becoming powerful tools in the construction of complex molecular skeletons.[1,2]
The following is a selection of recent articles in this field from Angewandte Chemie, Chemistry—A European Journal, European Journal of Organic Chemistry and Advanced Synthesis & Catalysis. It is updated on a daily basis, so stay tuned!
[1] P. I. Dalko, L. Moisan,
Angew. Chem. 2001, 113, 3840; Angew. Chem. Int. Ed. 2001, 40, 3726
Angew. Chem. 2004, 116, 5248; Angew. Chem. Int. Ed. 2004, 43, 5138.
[2] Special issue of Adv. Synth. Catal. 2004, 346, Nr. 9-10.
Hua Zhao, Yu-Bao Lan, Zhao-Min Liu, Yong Wang, Xing-Wang Wang, Jing-Chao Tao
Enantioselective Construction of Spiro[2H-pyran-3,4'-indoline] by a Systematic Michael/Reduction/Cyclization Sequence Triggered by the Asymmetric Conjugate Addition of Ketones to Isatylidenemalononitriles [Full Paper]
Alberto Fraile, Daniele M. Scarpino Schietroma, Anna Albrecht, Rebecca L. Davis, Karl Anker Jørgensen
Asymmetric Synthesis of Hexahydropyrrolo-isoquinolines by an Organocatalytic Three-Component Reaction [Communication]
Merging three in one by a three-component organocatalytic asymmetric reaction of imines, α-bromoesters, or ketone with α,β-unsaturated aldehydes provides optically active pyrrolo-isoquinolines—an important class of molecules in life science. The reaction proceeds with excellent enantioselectivity and a number of transformations of the products obtained demonstrated the potential of the new reaction.
Chem. Eur. J., February 10, 2012, DOI: 10.1002/chem.201200108
Markus B. Schmid, Kirsten Zeitler, Ruth M. Gschwind
Stabilization of Proline Enamine Carboxylates by Amine Bases [Full Paper]
Deprotonate me if you can: Deprotonation of the proline acid function is manifested by an increase in the amount of enamine intermediates upon reaching a critical pKaH. The in situ NMR spectroscopic detection of a prolinate–DBUH+ ion pair supports the reversal of enantioselectivity of proline-catalyzed aminations by disabling the bifunctional activity of proline (see figure).
Chem. Eur. J., February 10, 2012, DOI: 10.1002/chem.201102660
Peter A. Jordan, Scott J. Miller
An Approach to the Site-Selective Deoxygenation of Hydroxy Groups Based on Catalytic Phosphoramidite Transfer [Communication]
Selective: The deoxygenation of simple and complex natural products employing a readily synthesized phosphoramidite and tetrazole catalysts can be executed as a two-step process, without the need to isolate intermediate deoxygenation precursors. Furthermore, a peptide-based tetrazole catalyst controls the site selectivity of deoxyerythromycin synthesis (see scheme), thus overcoming the notorious challenges with unprotected erythromycin A.
Angew. Chem. Int. Ed., February 8, 2012, DOI: 10.1002/anie.201109033
Ulrich Hennecke
New Catalytic Approaches towards the Enantioselective Halogenation of Alkenes [Focus Review]
Technical difficulties: Enantioselective, electrophilic halogen additions to alkenes have often been described as difficult reactions. Recently, this problem has been addressed with many novel catalytic methods. In this focus review these methods will be summarized highlighting common themes and mechanistic considerations.
Chem. Asian J., February 7, 2012, DOI: 10.1002/asia.201100856
Xin Li, Yue-Yan Zhang, Xiao-Song Xue, Jia-Lu Jin, Bo-Xuan Tan, Cong Liu, Nan Dong, Jin-Pei Cheng
Asymmetric Michael Addition Reactions between 3-Substituted Benzofuran-2(3H)-ones and 1,1-Bis(phenylsulfonyl)ethylene Catalyzed by Bifunctional Catalysts Containing Tertiary Amine and Thiourea Groups [Full Paper]
Jianmin Wang, Jie Chen, Choon Wee Kee, Choon-Hong Tan
Enantiodivergent and γ-Selective Asymmetric Allylic Amination [Communication]
Double agent: The title reaction using the guanidine catalyst 1 can deliver both enantiomers of the product with excellent enantioselectivity by judicious choice of the double bond geometry of the the β,γ-unsaturated carbonyl compound. Computational studies reveal the possible origin of the inversed enantioselectivity, and the potential for enantiodivergent synthesis chiral amine-containing substrates is attractive.
Angew. Chem. Int. Ed., January 27, 2012, DOI: 10.1002/anie.201107317
Reed T. Larson, Michael D. Clift, Regan J. Thomson
Total Synthesis of the Galbulimima Alkaloid (−)-GB17 [Communication]
A tale of two Michaels: The first enantioselective total synthesis of (−)-GB17 is reported. Construction of this unique naphthoquinolizinone skeleton was achieved by two stereoselective intramolecular Michael additions, one under catalyst control and the other under substrate control.
Angew. Chem. Int. Ed., January 27, 2012, DOI: 10.1002/anie.201108227
Daniel A. DiRocco, Elizabeth L. Noey, K. N. Houk, Tomislav Rovis
Catalytic Asymmetric Intermolecular Stetter Reactions of Enolizable Aldehydes with Nitrostyrenes: Computational Study Provides Insight into the Success of the Catalyst [Communication]
Fluorine helps: A fluorinated triazolium salt pre-catalyst has been developed that efficiently promotes the asymmetric intermolecular Stetter reaction of enolizable aldehydes and nitrostyrenes (see scheme). Trans fluorination of the catalyst architecture results in unparalleled reactivity and enantioselectivity in the desired transformation. A DFT study provides evidence of an electrostatic interaction as the source of the increased enantio-induction.
Angew. Chem. Int. Ed., January 26, 2012, DOI: 10.1002/anie.201107597
Xianxing Jiang, Xiaomei Shi, Shoulei Wang, Tao Sun, Yiming Cao, Rui Wang
Bifunctional Organocatalytic Strategy for Inverse-Electron-Demand Diels–Alder Reactions: Highly Efficient In Situ Substrate Generation and Activation to Construct Azaspirocyclic Skeletons [Communication]
Skeletons in the flask: The first highly enantioselective organocatalytic version of the title reaction using an in situ substrate generation/activation catalytic mode is described (see scheme). The reaction provides an efficient enantioselective construction of functionalized azaspirocyclic skeletons. The in situ generation of the enolate provides a new way in which to use this important nucleophile in organic synthesis.
Angew. Chem. Int. Ed., January 23, 2012, DOI: 10.1002/anie.201107716
Yuetao Zhang, Eugene Y.-X. Chen
Conjugate-Addition Organopolymerization: Rapid Production of Acrylic Bioplastics by N-Heterocyclic Carbenes [Communication]
It’s rapid and selective: In contrast to the dimerization of α,β-unsaturated esters (acrylics) by carbene 3, the more nucleophilic carbene 2 selectively forms the single-addition product, and 1, the most nucleophilic carbene of the series, polymerizes acrylics. The biomass-derived methylene butyrolactones are quantitatively polymerized to produce medium- to high-molecular-weight bioplastics in less than one minute at ambient temperature. Mes=1,4,6-trimethylphenyl, TOF=turnover frequency.
Angew. Chem. Int. Ed., January 23, 2012, DOI: 10.1002/anie.201108019
Maria Trifonidou, Christoforos G. Kokotos
Enantioselective Organocatalytic α-Alkylation of Ketones by SN1-Type Reaction of Alcohols [Full Paper]
Masahiro Terada, Yasunori Toda
Relay Catalysis Using a Rhodium Complex/Chiral Brønsted Acid Binary System: Enantioselective Reduction of a Carbonyl Ylide as the Reactive Intermediate [Communication]
Pass the baton: A one-pot relay catalysis for a carbonyl ylide formation/enantioselective reduction sequence using a dirhodium(II) tetracarboxylate and chiral phosphoric acid catalyst system is described. The four-step transformation involves a rhodium carbene complex, a carbonyl ylide, and an isobenzopyrylium, the enantioselective reduction of which yields isochromanone derivatives in good yield with high selectivity.
Angew. Chem. Int. Ed., January 19, 2012, DOI: 10.1002/anie.201107805
Bin Wu, Jian Chen, Mei-Qiu Li, Jin-Xin Zhang, Xiao-Ping Xu, Shun-Jun Ji, Xing-Wang Wang
Highly Enantioselective Synthesis of Spiro[cyclohexanone-oxindoles] and Spiro[cyclohexanone-pyrazolones] by Asymmetric Cascade [5+1] Double Michael Reactions [Full Paper]
![Highly Enantioselective Synthesis of Spiro[cyclohexanone-oxindoles] and Spiro[cyclohexanone-pyrazolones] by Asymmetric Cascade [5+1] Double Michael Reactions](http://www.wiley-vch.de/util/hottopics/img/ejoc201101529.jpg "Highly Enantioselective Synthesis of Spiro[cyclohexanone-oxindoles] and Spiro[cyclohexanone-pyrazolones] by Asymmetric Cascade [5+1] Double Michael Reactions")
An efficient approach to spiro compounds through cascade [5+1] double Michael reactions between divinyl ketones and oxindoles or N-protected pyrazolones in the presence of 9-amino-9-deoxy-epi-quinine and N-Boc-D-phenylglycine is reported. Multistereogenic spiro[cyclohexanone-oxindoles and -pyrazolones] are obtained with high yields (up to 98 %) and stereoselectivities (up to >20:1 dr, 99 % ee).
Hexin Xie, Shilei Zhang, Hao Li, Xinshuai Zhang, Sihan Zhao, Zian Xu, Xixi Song, Xinhong Yu, Wei Wang
Total Synthesis of Polyene Natural Product Dihydroxerulin by Mild Organocatalyzed Dehydrogenation of Alcohols [Communication]
Polyene synthesis: An efficient approach to the total synthesis of polyene natural product dihydroxrulin (1) is described. A novel, mild, direct organocatalytic IBX-mediated dehydrogenation process of simple alcohols to enals has been developed, which serves as a key step in the synthesis (see scheme).
Liu Song, Qi-Xiang Guo, Xing-Cheng Li, Juan Tian, Yun-Gui Peng
The Direct Asymmetric α Alkylation of Ketones by Brønsted Acid Catalysis [Communication]
Being direct: A Brønsted acid catalyzed α alkylation of ketones is described. The phosphoric acid 1 promotes this reaction to afford the desired products with high yields, high diastereoselectivities, and good to excellent enantioselectivites.
Lital Tuchman-Shukron, Scott J. Miller, Moshe Portnoy
Polymer-Supported Enantioselective Bifunctional Catalysts for Nitro-Michael Addition of Ketones and Aldehydes [Full Paper]
“L” is right: Introduction of an L-amino acid spacer in a polymer-supported bifunctional catalyst, based on a chiral diamine, imparts outstanding activity and stereoselectivity in nitro-Michael addition, whereas D-amino acids are a poor match for the particular diamine configuration (see scheme). The reactivity patterns of the new catalysts shed light on the reaction mechanism and the C-C bond-forming transition state.
Gábor Tárkányi, Péter Király, Tibor Soós, Szilárd Varga
Active Conformation in Amine–Thiourea Bifunctional Organocatalysis Preformed by Catalyst Aggregation [Communication]
Self-activation: Takemoto's catalyst gains access to its active conformation by equilibrating between its hydrogen-bonded intra- and intermolecular interactions in apolar aprotic solvents. By destabilization of the inactive monomeric conformations, the extended anti–anti thiourea conformation is preformed in the assembly. On leaving the assembly, this transient conformation has a structural preference to become a catalytically active monomeric species that has the potency for dual activation (see scheme).
Kwang-Su Choi, Sung-Gon Kim
Asymmetric Organocatalytic Michael Addition–Cyclization Cascade Reaction of Nitroalkanes with o-Hydroxycinnamaldehydes [Short Communication]
A catalytic enantioselective Michael addition–cyclization reaction of nitroalkanes with o-hydroxycinnamaldehydes has been established by using a diphenylprolinol TMS ether as an organocatalyst. The reaction afforded the corresponding 4-substituted chroman-2-ols in excellent yields with high levels of enantioselectivities (95 to >99 % ee).
Dhevalapally B. Ramachary, Y. Vijayendar Reddy
Dienamine Catalysis: An Emerging Technology in Organic Synthesis [Microreview]
This microreview describes the reaction engineering of dienamine catalysis for single-step syntheses of highly functionalized molecules such as natural products orbioactive compounds. Here we discuss the entire saga of dienamine chemistry from “preformed dienamines” to “in situ dienamines” and its evolution as unique technology in organic synthesis.
Hélène Pellissier
Recent Developments in Asymmetric Organocatalytic Domino Reactions [Review]
Kiyoun Lee, Hyoungsu Kim, Jiyong Hong
Stereoselective Synthesis of Tetrahydropyrans through Tandem and Organocatalytic Oxa-Michael Reactions: Synthesis of the Tetrahydropyran Cores of ent-(+)-Sorangicin A [Full Paper]
The tandem and organocatalytic oxa-Michael reactions of α,β-unsaturated aldehydes were explored and applied to the stereoselective synthesis of structurally complex tetrahydropyrans.
Maitane Fernández, Efraím Reyes, Jose L. Vicario, Dolores Badía, Luisa Carrillo
Organocatalytic Enantioselective Synthesis of Pyrazolidines, Pyrazolines and Pyrazolidinones [Communication]
Junxing Xu, Yulai Hu, Danfeng Huang, Ke-Hu Wang, Changming Xu, Teng Niu
Thiourea-Catalyzed Enantioselective Fluorination of β-Keto Esters [Full Paper]
Shin A. Moteki, Jianwei Han, Satoru Arimitsu, Matsujiro Akakura, Keiji Nakayama, Keiji Maruoka
An Achiral-Acid-Induced Switch in the Enantioselectivity of a Chiral cis-Diamine-Based Organocatalyst for Asymmetric Aldol and Mannich Reactions [Communication]
Pick and choose: The asymmetric synthesis of two different enantiomeric products has been achieved through the use of a single organocatalyst with or without achiral organic acid additives (see scheme). These additives may assist in altering the substrate orientations at the catalytic center, leading to efficient enantiomeric inversions in both aldol and Mannich products.
Ellen Zandvoort, Edzard M. Geertsema, Bert-Jan Baas, Wim J. Quax, Gerrit J. Poelarends
Bridging between Organocatalysis and Biocatalysis: Asymmetric Addition of Acetaldehyde to β-Nitrostyrenes Catalyzed by a Promiscuous Proline-Based Tautomerase [Communication]
Non-natural beauty: The enzyme 4-oxalocrotonate tautomerase (4-OT) promiscuously (i.e., with non-natural activity) catalyzes the Michael-type addition of acetaldehyde to nitrostyrene. Catalysis likely proceeds via enamine formation of the amino-terminal proline residue of 4-OT with acetaldehyde (see picture), reminiscent of organocatalysis. High stereoselectivity, low catalyst loading, and water as reaction medium characterize this methodology.
Taichi Kano, Sunhwa Song, Yasushi Kubota, Keiji Maruoka
Highly Diastereo- and Enantioselective Mannich Reactions of Synthetically Flexible Ketimines with Secondary Amine Organocatalysts [Communication]
High selectivity: A highly diastereo- and enantioselective Mannich reaction between a synthetically flexible ketimine and aldehydes has been developed. The syn- or anti-Mannich products contain tetrasubstituted chiral carbon centers and were obtained with almost complete stereoselectivity by using either L-proline or an axially chiral aminosulfonamide, respectively, as the catalyst (see scheme, Tf=trifluoromethanesulfonyl).
Chang Guo, Jin Song, Jian-Zhou Huang, Peng-Hao Chen, Shi-Wei Luo, Liu-Zhu Gong
Core-Structure-Oriented Asymmetric Organocatalytic Substitution of 3-Hydroxyoxindoles: Application in the Enantioselective Total Synthesis of (+)-Folicanthine [Communication]
Something constructive: The title reaction involving 3-hydroxyoxindoles gives 3,3'-disubstituted oxindoles with concomitant generation of an all-carbon quaternary stereogenic center in high yield and excellent enantioselectivity. This reaction enabled the enantioselective construction of hexahydropyrroloindole skeletons and the first catalytic enantioselective total synthesis of (+)-folicanthine.
Cristina Pubill-Ulldemolins , Amadeu Bonet, Carles Bo, Henrik Gulyás, Elena Fernández
Activation of Diboron Reagents with Brønsted Bases and Alcohols: An Experimental and Theoretical Perspective of the Organocatalytic Boron Conjugate Addition Reaction [Full Paper]
The simplest method to activate diboron reagents and make them suitable for incorporation in targeted organic molecules seems to be deprotonation of MeOH by base (e.g., Verkade's base) to generate the methoxide anion, which interacts with the diboron reagent to give a nucleophilic Lewis acid–base adduct that promotes the β-boration of α,β-unsaturated carbonyl substrates. Methanol protonates the intermediate to generate the product and another methoxide anion (see scheme).
Biao Xu, Zhi-Lei Guo, Wan-Yan Jin, Zhi-Ping Wang, Yun-Gui Peng, Qi-Xiang Guo
Multistep One-Pot Synthesis of Enantioenriched Polysubstituted Cyclopenta[b]indoles [Communication]
![Multistep One-Pot Synthesis of Enantioenriched Polysubstituted Cyclopenta[b]indoles](http://www.wiley-vch.de/util/hottopics/img/anie201107308.gif "Multistep One-Pot Synthesis of Enantioenriched Polysubstituted Cyclopenta[b]indoles")
Simple steps, complex result: Consecutive organo-catalyzed reactions of 3-indolylmethanol compounds with aldehydes and N-protected indoles lead to the formation of structurally complex cyclopenta[b]indoles (see scheme, Bn=benzyl). These one-pot multistep reactions have a broad substrate scope and give the products in high yields, and with excellent diastereoselectivities and enantioselectivities.
Giulia Bergonzini, Paolo Melchiorre
Dioxindole in Asymmetric Catalytic Synthesis: Routes to Enantioenriched 3-Substituted 3-Hydroxyoxindoles and the Preparation of Maremycin A [Communication]
Taming the reactivity: Understanding the nucleophilicity of dioxindole under different reaction conditions is key to a direct and easy access to valuable spiro oxindole γ butyrolactones and 3-substituted 3-hydroxyoxindole derivatives in excellent yields and enantioselectivities (see scheme). The preparation of maremycin A serves as an example for the potential usefulness of this previously unexplored reactivity in natural product synthesis.
Ai-Bao Xia, Dan-Qian Xu, Chao Wu, Long Zhao, Zhen-Yuan Xu
Organocatalytic Diels–Alder Reactions Catalysed by Supramolecular Self-Assemblies Formed from Chiral Amines and Poly(alkene glycol)s [Communication]
Self-assembled catalyst: A new kind of chiral supramolecular organocatalyst, self-assembled from chiral amines and poly(alkene glycol)s, was developed. The resulting self-assemblies were found to be highly efficient in the asymmetric catalysis of the unusual Diels–Alder reaction between cyclohexenones and nitrodienes, nitroenynes or nitroolefins, giving excellent chemo-, regio- and enantioselectivities (see scheme).
André Grossmann, Dieter Enders
N-Heterocyclic Carbene Catalyzed Domino Reactions [Minireview]
Every Jack will find his Jill: Uniting unique activation modes of N-heterocyclic carbene (NHC) catalysts with the concept of domino reactions (see picture, EWG=electron-withdrawing group), a new fast-growing field came into the spotlight in last three years. The state of the art of this field is presented and the definition of the domino reactions for the NHC catalysis is re-considered.
Xiaowei Dou, Xiaoyu Han, Yixin Lu
From the Feist–Bénary Reaction to Organocatalytic Domino Michael–Alkylation Reactions: Asymmetric Synthesis of 3(2 H)-Furanones [Communication]
It all adds up! A modified Feist–Bénary reaction employing a domino Michael–alkylation sequence was designed for the enantioselective synthesis of 3(2 H)-furanones. L-Threonine-derived tertiary amine/thiourea catalysts were prepared for the first time; such catalysts promoted the designed domino Michael–alkylation reactions in a highly enantioselective manner (see scheme).
Bin Tan, Xiaofei Zeng, Wendy Wen Yi Leong, Zugui Shi, Carlos F. Barbas, III Guofu Zhong
Core Structure-Based Design of Organocatalytic [3+2]-Cycloaddition Reactions: Highly Efficient and Stereocontrolled Syntheses of 3,3'-Pyrrolidonyl Spirooxindoles [Communication]
![Core Structure-Based Design of Organocatalytic [3+2]-Cycloaddition Reactions: Highly Efficient and Stereocontrolled Syntheses of 3,3'-Pyrrolidonyl Spirooxindoles](http://www.wiley-vch.de/util/hottopics/img/chem201103449.gif "Core Structure-Based Design of Organocatalytic [3+2]-Cycloaddition Reactions: Highly Efficient and Stereocontrolled Syntheses of 3,3'-Pyrrolidonyl Spirooxindoles")
Extraordinary levels of stereocontrol were achieved in an efficient organocatalytic asymmetric [3+2]-cycloaddition reaction between an α-isothiocyanato imide and various methyleneindolinones. Simple precursors were used for the rapid construction of spirocyclic oxindole derivatives with high enantiopurity and structural diversity, thus providing a new avenue of significance to medicinal chemistry and diversity-oriented synthesis.
Wilfried Raimondi, Damien Bonne, Jean Rodriguez
1,2-Dicarbonyl Compounds as Pronucleophiles in Organocatalytic Asymmetric Transformations [Highlight]
Organocatalysis likes them too! 1,2-dicarbonyl compounds possess high synthetic potential because of their adjacent multiple reactive centers. Recent contributions indicate that these reactive species, with an appropriate activation mode, may also act as efficient pronucleophiles in asymmetric organocatalyzed sequential or domino transformations including C-C or C-N bond formation (see scheme).
Charles C. J. Loh, Dieter Enders
Exploiting the Electrophilic Properties of Indole Intermediates: New Options in Designing Asymmetric Reactions [Highlight]
Think electrophilic: While the classical π-excessive indole is well-known for its electrophilic substitutions at position C3, recent advances in asymmetric catalysis resulted in a surge in utilizing the less discussed electrophilic properties of iminium-type intermediates (see picture) in complex annulations of indoles. Advances in AuI catalysis also allow an umpolung of the classical indole C3 reactivity.
Marianne Steurer, Kim L. Jensen, Dennis Worgull, Karl Anker Jørgensen
Enantioselective One-Pot Synthesis of α-Amino Esters by a Phosphine-Catalyzed [3+2]-Cycloaddition Reaction [Communication]
![Enantioselective One-Pot Synthesis of α-Amino Esters by a Phosphine-Catalyzed [3+2]-Cycloaddition Reaction](http://www.wiley-vch.de/util/hottopics/img/chem201103502.gif "Enantioselective One-Pot Synthesis of α-Amino Esters by a Phosphine-Catalyzed [3+2]-Cycloaddition Reaction")
Phosphines go one-pot: The one-pot synthesis of cyclic α-amino esters from azlactones and allenes by a phosphine-catalyzed [3+2]-cycloaddition reaction followed by a ring opening of the azlactone moiety is presented. The products are isolated as single regioisomers in good overall yields and high enantioselectivities (up to 95 % ee). The possibility for easy modifications of the obtained products was demonstrated by synthesizing an amino acid and an α-hydroxy-β-ketoester.
Joe P. Richmond
New Developments in Advanced Synthesis & Catalysis: Growth and High-Impact Research for Green Organic Synthesis [Commentary]
Michail Tsakos, Christoforos G. Kokotos
Organocatalytic “Difficult” Michael Reaction of Ketones with Nitrodienes Utilizing a Primary Amine–Thiourea Based on Di-tert-butyl Aspartate [Full Paper]
The combination of (1R,2R)-1,2-diphenylethylene-1,2-diamine and di-tert-butyl (S)-aspartate provided an excellent thiourea organocatalyst for the “difficult” Michael reaction between methyl ketones and nitrodienes.
Lotfi Tak-Tak, Hamid Dhimane, Peter I. Dalko
Asymmetric α Alkylation of Aldehydes: Efficiency with Elegance [Highlight]
Simple and practical: Direct intermolecular α alkylation reactions by SN1-type transformations have been developed and offer flexible and robust routes to major compound classes, for which the direct preparations were unavailable before.
Huan Liang, Marco A. Ciufolini
Chiral Hypervalent Iodine Reagents in Asymmetric Reactions [Highlight]
All hyper: Recent advances in the area of chiral hypervalent iodine reagents, notably by the groups of Kita, Ishihara, and Fujita, enable some oxidative transformations to be conducted in an enantioselective manner and with asymmetric inductions in the range of 86–95 % ee (see scheme, Mes=mesityl). This contribution highlights representative reactions, reagent/catalyst design, and mechanistic aspects of the reported transformations.
Lucie E. Zimmer, Christof Sparr, Ryan Gilmour
Fluorine Conformational Effects in Organocatalysis: An Emerging Strategy for Molecular Design [Minireview]
F in control: Conformational effects of fluorinated molecules have hitherto mainly been restricted to bio-organic chemistry. The renaissance of organocatalysis, however, offers the possibility to exploit many of the stereoelectronic and electrostatic effects of fluorinated organic molecules for molecular preorganization. In this Minireview, we highlight examples of catalyst refinement by the introduction of an aliphatic C-F bond which functions as a chemically inert steering group for conformational control.
Silvia Reboredo, Jose L. Vicario, Dolores Badía, Luisa Carrillo, Efraím Reyes
Complete 2,5-Diastereocontrol in the Organocatalytic Enantioselective [3+2] Cycloaddition of Enals with Azomethine Ylides Derived from α-Iminocyanoacetates: Asymmetric Synthesis of Pyrrolidines with Four Stereocentres [Communication]
Aijun Lin, Haibin Mao, Xi Zhu, Huiming Ge, Renxiang Tan, Chengjian Zhu, Yixiang Cheng
Organocatalytic Asymmetric C-S Bond Formation: Synthesis of α-Methylene-β-mercapto Esters with Simple Alkyl Thiols [Communication]
Mattia R. Monaco, Marco Bella
A Formidable Challenge: Catalytic Asymmetric Dichlorination [Highlight]
The missing piece: The long-pursued asymmetric catalytic dichlorination reaction has recently been reported (see scheme). The multiple issues faced to develop such an elusive target are discussed.
Nicolas De Rycke, François Couty, Olivier R. P. David
Increasing the Reactivity of Nitrogen Catalysts [Review]
From pyridine at the dawn of the 20th century, through DMAP during the Cold War, to the most recent chiral isothioureas, the progress made in the field of nitrogen-centred Lewis base catalysts are reviewed under the light of physical organic chemistry.
Michael Schwarz, Oliver Reiser
Metal or No Metal: That Is the Question! [Highlight]
Dihydroxylation with peroxides: The 1,2-dihydroxy structural motif, which can be generated from a C=C bond, occurs widely in organic compounds. Advances in the syn dihydroxylation of alkenes with cyclic acyl peroxides broaden the application of this transformation for a variety of olefins (see scheme). In recent studies the scope, limitations, and a mechanistic pathway have been delineated.
Łukasz Albrecht, Hao Jiang, Karl Anker Jørgensen
A Simple Recipe for Sophisticated Cocktails: Organocatalytic One-Pot Reactions—Concept, Nomenclature, and Future Perspectives [Minireview]
It's great, but what shall we call it? Asymmetric organocatalysis has been successfully incorporated in many multistep one-pot sequences (see picture; A–G are reagents). In this Minireview, an easy-to-use classification system for the systematic and informative description of one-pot reactions is introduced. Selected important contributions within the field of organocatalytic one-pot reactions are reviewed according to this new system.
Isabelle Dion, André M. Beauchemin
Asymmetric Brønsted Acid Catalysis Enabling Hydroaminations of Dienes and Allenes [Highlight]
Acid treatment: Toste et al. recently unveiled a new pathway for asymmetric Brønsted acid catalysis of reactions involving dienes or allenes, and achieved highly efficient intramolecular hydroamination and hydroarylation reactions (see scheme). The P=S bond proved necessary for reactivity, and dithiophosphoric acids emerged as efficient catalysts. The association/displacement sequence led to chiral pyrrolidines and isoxazolidines in excellent yields and ee values.
Sunil V. Pansare, Eldho K. Paul
The Organocatalytic Vinylogous Aldol Reaction: Recent Advances [Minireview]
Who needs metals? A review of the development and application of the organocatalytic version of the vinylogous aldol reaction is provided. Two variants of this reaction are discussed in detail, the organocatalysed adaptation of the vinylogous Mukaiyama aldol reaction and the more recent direct vinylogous aldol reaction of enals and 2(5H) furanones.
Carl A. Busacca, Daniel R. Fandrick, Jinhua J. Song, Chris H. Senanayake
The Growing Impact of Catalysis in the Pharmaceutical Industry [Review]
Rik P. Megens, Gerard Roelfes
Asymmetric Catalysis with Helical Polymers [Concept]
Natural born catalysts: Inspired by nature, the use of helical polymer catalysts is emerging as an attractive new approach to achieve asymmetric catalysis (see figure). In this Concept article the various approaches, designs, and applications in asymmetric catalysis will be discussed.
Magnus Rueping, Boris J. Nachtsheim, Winai Ieawsuwan, Iuliana Atodiresei
Modulating the Acidity: Highly Acidic Brønsted Acids in Asymmetric Catalysis [Minireview]
Chiral highly acidic Brønsted acids B*-H (see scheme, bottom) are efficient organocatalysts for numerous enantioselective reactions. Owing to their high acidity, these catalysts are suitable for the activation of imines, carbonyl compounds, and other weakly basic substrates. The formation of chiral contact-ion pairs (see scheme, top) implicates completely new modes of activation for asymmetric synthesis.
Susy Piovesana, Daniele M. Scarpino Schietroma, Marco Bella
Multiple Catalysis with Two Chiral Units: An Additional Dimension for Asymmetric Synthesis [Minireview]
Divide et Impera: A newly emerging aspect of catalysis that involves the use of two chiral catalysts simultaneously is described (see picture). This Minireview highlights the features of the two-catalyst reactions and the synthetic applications of the methods.
Christian E. Müller, Peter R. Schreiner
Organocatalytic Enantioselective Acyl Transfer onto Racemic as well as meso Alcohols, Amines, and Thiols [Review]
Ode to the perfect pass: Acyl transfer is one of the most vibrant areas of organocatalysis. Such transfer reactions, in part mimicking nature, are steadily turning kinetic resolutions as well as enantioselective transformations into practical tools for the preparation of basic chiral building blocks.
José Alemán, Alejandro Parra, Hao Jiang, Karl Anker Jørgensen
Squaramides: Bridging from Molecular Recognition to Bifunctional Organocatalysis [Minireview]
New dimensions for squaramides: In this minireview, squaramides are presented from their roots as artificial anion receptors in molecular recognition studies to the new advances in their application in asymmetric organocatalysis as powerful bifunctional hydrogen-bonding catalysts. The main features of the squaramido functionality and direct comparison with analogous ureas and thioureas are also discussed.
Armido Studer, Dennis P. Curran
Organocatalysis and C-H Activation Meet Radical- and Electron-Transfer Reactions [Essay]
A radical outlook: Recently published “organocatalytic C-H activation reactions” have now been interpreted as base-promoted homolytic substitutions. The addition of an aryl radical to an arene followed by deprotonation (see above) and electron transfer form part of the chain reaction. Although these new results are not conceptual breakthroughs, they could be experimental breakthroughs because they presage new transformations in radical (anion) chemistry.
Pengfei Li, Sau Hing Chan, Albert S. C. Chan, Fuk Yee Kwong
Organocatalytic Asymmetric Aldol Reaction of Ketones with β,γ-Unsaturated α-Keto Esters: An Efficient Access to Chiral Tertiary Alcohol Skeletons [Update]
Pier Giorgio Cozzi, Enrico Emer, Andrea Gualandi
Atroposelective Organocatalysis [Highlight]
Spin off: The synthesis of optically active biaryl compounds using enantioselective organocatalysis is highlighted. Foldamers coupled with organocatalysis, specifically hydrogen-bonding interactions (see scheme; Boc=tert-butoxycarbonyl), can be used to access compounds with a stereogenic axis. New selective syntheses of atropoisomers can be inspired by these findings, thus enhancing the use of atropoisomeric compounds in synthesis and catalysis.
Carine Vaxelaire, Philipp Winter, Mathias Christmann
One-Pot Reactions Accelerate the Synthesis of Active Pharmaceutical Ingredients [Highlight]
All in one: A one-pot synthesis of the dipeptidylpeptidase IV selective inhibitor ABT-341 (see structure) by using an “uninterrupted sequence of reactions” has been developed. This strategy broadens the spectrum of one-pot reactions and is poised to speed up the synthesis of medicinally relevant drug compounds.
Sebastian Schenker, Alexandru Zamfir, Matthias Freund, Svetlana B. Tsogoeva
Developments in Chiral Binaphthyl-Derived Brønsted/Lewis Acids and Hydrogen-Bond-Donor Organocatalysis [Microreview]
This microreview discusses recent advances in the application of a series of binaphthyl-derived organocatalysts including, among others, N-triflyl phosphoramides, dicarboxylic acids, BINOLs, BAMOLs, and bis-thioureas. The achievements with in situ formed binaphthyl-derived silicon Lewis acids are also presented.
Hélène Pellissier
Organocatalyzed Dynamic Kinetic Resolution [Review]
Jeffrey N. Johnston
A Chiral N-Phosphinyl Phosphoramide: Another Offspring for the Sage Phosphoric Acid Progenitor [Highlight]
Nitrogen enriched: The continuing quest for Brønsted acid catalysts that address unmet selectivity needs in organic synthesis has resulted in a new chiral phosphoric acid derivative. At the heart of this catalyst is a hydrogen-bond donor (N-H) that promotes an enantioselective intramolecular addition of oxygen (OH) to an azomethine (C=N). Diversity within a privileged chiral architecture invariably leads to new catalytic enantioselective chemical reactions.
Andrea-Nekane R. Alba, Ramon Rios
Oxazolones in Organocatalysis, New Tricks for an Old Reagent [Focus Review]
Trick and treat: Oxazolones or azlactones are among the most-common starting materials for the synthesis of quaternary amino acids. With the “renaissance” of organocatalysis, oxalactones have emerged as important starting materials for a range of new organocatalytic asymmetric methodologies. EWG=electron-withdrawing group.
Guillem Valero, Xavier Companyó, Ramon Rios
Enantioselective Organocatalytic Synthesis of Fluorinated Molecules [Review]
Previously on organocatalytic synthesis of fluorinated molecules: The enantioselective synthesis of fluorinated molecules has attracted much interest from chemical community due to their unique structural and electronic properties. In this review, the most important organocatalytic enantioselective methodologies to obtain fluorinated molecules are discussed.
© Wiley-VCH 2011.
RSS feed![Enantioselective Construction of Spiro[2H-pyran-3,4'-indoline] by a Systematic Michael/Reduction/Cyclization Sequence Triggered by the Asymmetric Conjugate Addition of Ketones to Isatylidenemalononitriles](http://www.wiley-vch.de/util/hottopics/img/ejoc201101810.jpg "Enantioselective Construction of Spiro[2H-pyran-3,4'-indoline] by a Systematic Michael/Reduction/Cyclization Sequence Triggered by the Asymmetric Conjugate Addition of Ketones to Isatylidenemalononitriles")
![Complete 2,5-Diastereocontrol in the Organocatalytic Enantioselective [3+2] Cycloaddition of Enals with Azomethine Ylides Derived from α-Iminocyanoacetates: Asymmetric Synthesis of Pyrrolidines with Four Stereocentres](http://www.wiley-vch.de/util/hottopics/img/adsc201100432.gif "Complete 2,5-Diastereocontrol in the Organocatalytic Enantioselective [3+2] Cycloaddition of Enals with Azomethine Ylides Derived from α-Iminocyanoacetates: Asymmetric Synthesis of Pyrrolidines with Four Stereocentres")
