Hot TopicsWiley-VCH

ASCEurJOCChem Eur JAngewandte

Organocatalysis

ACh cover 24/2003The term organocatalysis describes the acceleration of chemical reactions through the addition of a substoichiometric quantity of an organic compound. The interest in this field has increased spectacularly in the last few years as result of both the novelty of the concept and, more importantly, the fact that the efficiency and selectivity of many organocatalytic reactions meet the standards of established organic reactions. Organocatalytic reactions are becoming powerful tools in the construction of complex molecular skeletons.[1,2]

[1] P. I. Dalko, L. Moisan,
Angew. Chem. 2001, 113, 3840; Angew. Chem. Int. Ed. 2001, 40, 3726
Angew. Chem. 2004, 116, 5248; Angew. Chem. Int. Ed. 2004, 43, 5138.

[2] Special issue of Adv. Synth. Catal. 2004, 346, Nr. 9-10.

Recent Articles

RSS feed

Phosphine-Catalyzed Asymmetric Umpolung Addition of Trifluoromethyl Ketimines to Morita–Baylis–Hillman Carbonates

Phosphine‐Catalyzed Asymmetric Umpolung Addition of Trifluoromethyl Ketimines to Morita–Baylis–Hillman Carbonates

Flip flop: The title reaction provides facile access to optically active trifluoromethyl amines with a tertiary stereocenter under mild reaction conditions. The salient features of this reaction include a general substrate scope, good yields, and high enantioselectivities. Boc=tert-butoxycarbonyl.

[Communication]
Peng Chen, Zhenting Yue, Junyou Zhang, Xi Lv, Lei Wang, Junliang Zhang
Angew. Chem. Int. Ed., September 16, 2016, DOI: 10.1002/anie.201607918. Read article

Stereoselective Organocatalyzed Synthesis of α-Fluorinated β-Amino Thioesters and Their Application in Peptide Synthesis

Stereoselective Organocatalyzed Synthesis of α‐Fluorinated β‐Amino Thioesters and Their Application in Peptide Synthesis

Get rid of the middleman: A broad range of α-fluorinated β-amino thioesters were formed with high diastereo- and enantioselectivity in the presence of 1 mol % of a cinchona-alkaloid–squaramide catalyst (see scheme; PG=protecting group). The resulting preactivated fluorinated β-amino acids were readily incorporated into α,β-peptides without the need for coupling reagents and had a defined conformation that was retained within the peptides.

[Communication]
Elena Cosimi, Oliver D. Engl, Jakub Saadi, Marc-Olivier Ebert, Helma Wennemers
Angew. Chem. Int. Ed., September 16, 2016, DOI: 10.1002/anie.201607146. Read article

Catalytic Enantioselective Synthesis of C1- and C2-Symmetric Spirobiindanones through Counterion-Directed Enolate C-Acylation

Catalytic Enantioselective Synthesis of C1‐ and C2‐Symmetric Spirobiindanones through Counterion‐Directed Enolate C‐Acylation

Spirocyclic architectures: A catalytic enantioselective route to C1- and C2-symmetric 2,2′-spirobiindanones has been realized through an intramolecular enolate C-acylation. This reaction employs a chiral counterion to direct the acylation of an in situ generated enolate, and constitutes the first example of an enantioselective phase-transfer mediated C-acylation.

[Communication]
Benjamin F. Rahemtulla, Hugh F. Clark, Martin D. Smith
Angew. Chem. Int. Ed., September 15, 2016, DOI: 10.1002/anie.201607731. Read article

Asymmetric Mannich Reaction of Aryl Methyl Ketones with Cyclic Imines Benzo[e][1,2,3]oxathiazine 2,2-Dioxides Catalyzed by Cinchona Alkaloid-based Primary Amines

Aryl ketones represent problematic substrates for asymmetric Mannich reactions due to a large steric hindrance exhibited by this compound species. A highly enantioselective direct Mannich reaction of aryl methyl ketones with cyclic imines benzo[e][1,2,3]oxathiazine 2,2-dioxides could be successfully carried out, utilizing a combination of cinchona alkaloid derived primary amines with TFA, for the primary amines feature a superior catalytic efficacy over secondary amines with a variety of sterically hindered carbonyl compounds as substrates. The reaction proceeded well with various cyclic imines in 89-97% ee, and with various aryl methyl ketones in 85-98% ee. Moreover, aryl carbonyl of a Mannich product could be transformed to ketoxime, further undergoing a Beckmann rearrangement to produce an amide compound while maintaining enantioselectivity.

[Full Paper]
Xiao-Yu Cui, Hui-Xin Duan, Yongna Zhang, You-Qing Wang
Chem. Asian J., September 12, 2016, DOI: 10.1002/asia.201601149. Read article

Insights into N-Heterocyclic Carbene-Catalyzed [4 + 2] Annulation Reaction of Enals with Nitroalkenes: Mechanisms, Origin of Chemo- and Stereoselectivity, and Role of Catalyst

In this paper, the density functional theory (DFT) has been employed to investigate the detailed mechanisms, origin of chemo- and stereoselectivity, and role of catalyst for the reaction of enals with nitroalkenes catalyzed by N-heterocyclic carbene (NHC). The calculated results disclose that the reaction contains seven steps, i.e., the nucleophilic attack on the , -unsaturated aldehyde by NHC, the [1, 2]-proton transfer for the formation of Breslow intermediate, the -protonation for affording enolate intermediate, the nucleophilic addition on the Re/Si face of enolate by the nitroalkenes, the [1, 5] proton transfer, the ring-closure process, and the regeneration of NHC. The addition on the Re/Si face of enolate is identified to be the stereocontrolling step, in which the chiral centers including -carbon of enals and -carbon of nitroalkenes are formed. Moreover, the reaction pathway leading to the RR-configured product has the lowest Gibbs free energy barrier, which is in agreement with the experimental observation. Furthermore, the analyses of electrophilic and nucleophilic Parr functions and global reactivity indexes (GRIs) have been performed to explore the origin of chemoselectivity and the role of catalyst. This theoretical work would provide valuable insights for the rational design of more effective organocatalyst for this kind of reactions with high stereoselectivities.

[Full Paper]
Linjie Zheng, Donghui Wei, Yang Wang, Yan Qiao
Chem. Asian J., September 08, 2016, DOI: 10.1002/asia.201601022. Read article

Enantioselective Nucleophilic β-Carbon-Atom Amination of Enals: Carbene-Catalyzed Formal [3+2] Reactions

Enantioselective Nucleophilic β‐Carbon‐Atom Amination of Enals: Carbene‐Catalyzed Formal [3+2] Reactions

Focus on the β-C: The aza-Michael addition of protected hydrazine to a catalytically generated unsaturated acyl azolium intermediate provides a highly efficient approach for enantioselective β-carbon-atom amination of enals. The heterocyclic products, prepared by using this method, are common scaffolds found in bioactive molecules, and can be readily transformed into β3-amino-acid derivatives. NHC=N-heterocyclic carbene.

[Communication]
Xingxing Wu, Bin Liu, Yuexia Zhang, Martin Jeret, Honglin Wang, Pengcheng Zheng, Song Yang, Bao-An Song, Yonggui Robin Chi
Angew. Chem. Int. Ed., September 06, 2016, DOI: 10.1002/anie.201606571. Read article

Iodoalkyne-Based Catalyst Mediated Activation of Thioamides through Halogen Bonding

Halogen bonding catalysis has recently gained increasing attention as a powerful tool to activate organic molecules. However, the variety of the catalyst structure has been quite limited so far. Herein we report the first example of the use of an iodoalkyne as a halogen bond donor catalyst. By using an iodoalkyne bearing a pentafluorophenyl group as a catalyst, thioamides were efficiently activated and reacted with 2-aminophenol to generate benzoxazoles in good yield. Mechanistic studies, including 13C-NMR spectroscopic analysis and several control experiments, provided concrete evidence that this catalytic activation is based on halogen bonding. Thus, the results obtained in this study demonstrated that iodoalkynes can serve as a new scaffold for future development of halogen bonding catalysis.

[Communication]
Akinobu Matsuzawa, Shiho Takeuchi, Kazuyuki Sugita
Chem. Asian J., August 31, 2016, DOI: 10.1002/asia.201601130. Read article

Kinetically Controlled α-Selective O-Glycosylation of Phenol Derivatives Using 2-Nitroglycals by a Bifunctional Chiral Thiourea Catalyst

Kinetically Controlled α‐Selective O‐Glycosylation of Phenol Derivatives Using 2‐Nitroglycals by a Bifunctional Chiral Thiourea Catalyst

The highly α-selective organocatalytic glycosylation of phenol derivatives using 2-nitroglycals has been developed. The stereoselectivity of this reaction was kinetically controlled by a bifunctional thiourea catalyst, and was applied to synthesis of glycopeptides.

[Communication]
Keisuke Yoshida, Yohei Kanoko, Kenichi Takao
Asian J. Org. Chem., August 25, 2016, DOI: 10.1002/ajoc.201600307. Read article

Facile Preparation of Flavinium Organocatalysts

Facile Preparation of Flavinium Organocatalysts

The green route: N(5)-Ethylated flavinium organocatalyst can be readily prepared without using any hazardous chemicals or inert atmosphere as previously required. This work breaks the limited application of flavinium oxidation catalysts in both laboratory and industrial synthesis.

[Communication]
Yukihiro Arakawa, Takahiro Oonishi, Takahiro Kohda, Keiji Minagawa, Yasushi Imada
ChemSusChem, August 24, 2016, DOI: 10.1002/cssc.201600846. Read article

CO2-based N-formylation of Amines Catalyzed by Fluoride and Hydroxide Anions

[Communication]
Martin Hulla, Felix Daniel Bobbink, Shoubhik Das, Paul J. Dyson
ChemCatChem, August 23, 2016, DOI: 10.1002/cctc.201601027. Read article

Aza-Michael Reactions of Isatin Imines: Deeper Insight and Origin of the Stereoselectivity

Aza‐Michael Reactions of Isatin Imines: Deeper Insight and Origin of the Stereoselectivity

Isatin aza-Michael reactions: The high enantioselectivity of the organocatalytic aza-Michael reaction of isatin imines is determined by several hydrogen bonds and π–π interactions, including an interaction of the sulfur atom of the thiourea catalyst and the aromatic π-electron system of the phenyl ring of imine.

[Full Paper]
Andrus Metsala, Sergei Žari, Tõnis Kanger
ChemCatChem, August 18, 2016, DOI: 10.1002/cctc.201600584. Read article

Promotion of Organic Reactions by Non-Benzenoid Carbocylic Aromatic Ions

[Review]
Demelza J. M. Lyons, Reece D. Crocker, Marcus Blümel, Thanh Vinh Nguyen
Angew. Chem. Int. Ed., August 10, 2016, DOI: 10.1002/anie.201605979. Read article

Synthesis of Diheteroatomic Five-Membered Heterocyclic Compounds from α,β-Unsaturated Aldehydes

Synthesis of Diheteroatomic Five‐Membered Heterocyclic Compounds from α,β‐Unsaturated Aldehydes

Channel 5: This Focus Review summarizes recent methods for the synthesis of five-membered N,N-, N,O-, and N,S-heterocycles based on the transformations of 2-alkenals. A multitude of catalytic and technological novelties, such as asymmetric metal- and organocatalysis, one-pot multicomponent reactions that proceed through domino, cascade, or tandem sequences, and microwave activation, have been used to afford a diverse range of products.

[Focus Review]
N. A. Keiko, N. V. Vchislo
Asian J. Org. Chem., August 01, 2016, DOI: 10.1002/ajoc.201600227. Read article

Asymmetric Aminocatalysis in the Synthesis of δ-Lactone Derivatives

Asymmetric Aminocatalysis in the Synthesis of δ‐Lactone Derivatives

Square up! A novel approach to 3,4-dihydrocoumarins utilizing the aminocatalytic, trienamine-mediated cycloaddition reaction between 2,4-dienals and ethyl coumarincarboxylates is presented. The reaction is promoted by a bifunctional aminocatalyst with a hydrogen-bonding squaramide structural unit. As a consequence, the stereochemical outcome is governed through the double hydrogen-bonding interactions between the hydrogen-bonding moiety of the catalyst and the dienophile.

[Communication]
Anna Albrecht, Anna Skrzyńska, Anna Pietrzak, Jan Bojanowski, Łukasz Albrecht
Asian J. Org. Chem., July 19, 2016, DOI: 10.1002/ajoc.201600272. Read article

Mass Spectrometric Back Reaction Screening of Quasi-Enantiomeric Products as a Mechanistic Tool

Mass Spectrometric Back Reaction Screening of Quasi‐Enantiomeric Products as a Mechanistic Tool

Observing back and forth: Mass spectrometric back reaction screening of quasi-enantiomeric products may serve as a valuable tool for examining the mechanism of an enantioselective catalytic process. By comparing the results from the forward and back reaction, direct evidence for the involvement of a catalytic intermediate in the enantioselective step can be obtained. The potential of this method is demonstrated for various organocatalytic asymmetric reactions.

[Personal Account]
Patrick G. Isenegger, Andreas Pfaltz
The Chemical Record, July 15, 2016, DOI: 10.1002/tcr.201600072. Read article

Organocatalytic [3+2] Cycloadditions of Barbiturate-Based Olefins with 3-Isothiocyanato Oxindoles: Highly Diastereoselective and Enantioselective Synthesis of Dispirobarbiturates

Organocatalytic [3+2] Cycloadditions of Barbiturate-Based Olefins with 3-Isothiocyanato Oxindoles: Highly Diastereoselective and Enantioselective Synthesis of Dispirobarbiturates

[Full Paper]
Hong-Wu Zhao, Ting Tian, Hai-Liang Pang, Bo Li, Xiao-Qin Chen, Zhao Yang, Wei Meng, Xiu-Qing Song, Yu-Di Zhao, Yue-Yang Liu
Adv. Synth. Catal., July 13, 2016, DOI: 10.1002/adsc.201600270. Read article.

N-Heterocyclic Carbene-Catalyzed Synthesis of Multi-Substituted Benzenes from Enals and α-Cyano-β-methylenones

N-Heterocyclic Carbene-Catalyzed Synthesis of Multi-Substituted Benzenes from Enals and α-Cyano-β-methylenones

[Communication]
Chun-Lin Zhang, Zhong-Hua Gao, Zhi-Qin Liang, Song Ye
Adv. Synth. Catal., June 20, 2016, DOI: 10.1002/adsc.201600531. Read article.

An Atropisomerically Enforced Phosphoric Acid for Organocatalytic Asymmetric Reactions

An Atropisomerically Enforced Phosphoric Acid for Organocatalytic Asymmetric Reactions

Three atropisomeric phosphoric acids for organocatalysis were obtained by a single Suzuki coupling reaction, and resolved by HPLC. All three catalysts could be used to promote organocatalytic reactions, rendering up to excellent enantioselectivity (98 % ee), confirming the potential of atropisomeric conformational control at the 3,3'-position of the BINOL core to infuence catalyst performance.

[Full Paper]
Luca Bernardi, Giada Bolzoni, Mariafrancesca Fochi, Michele Mancinelli, Andrea Mazzanti
Eur. J. Org. Chem., May 2, 2016, DOI: 10.1002/ejoc.201600296. Read article.

Catalytic Efficiency of Primary β-Amino Alcohols and Their Derivatives in Organocatalysis

Catalytic Efficiency of Primary β-Amino Alcohols and Their Derivatives in Organocatalysis

This review demonstrates the catalytic efficiency of primary β-amino alcohols and their derivatives in organocatalysis. These simple amino alcohols are inexpensive alternatives to other primary amino organocatalysts, being easy to synthesize and air-stable and offering the potential for introduction of different functional groups and alteration of steric sites.

[Microreview]
Ummareddy Venkata Subba Reddy, Madhu Chennapuram, Chigusa Seki, Eunsang Kwon, Yuko Okuyama, Hiroto Nakano
Eur. J. Org. Chem., April 26, 2016, DOI: 10.1002/ejoc.201600164. Read article.

Novel Base-Free Catalytic Wittig Reaction for the Synthesis of Highly Functionalized Alkenes

Novel Base-Free Catalytic Wittig Reaction for the Synthesis of Highly Functionalized Alkenes

Drop the base: A novel catalytic system based on a readily available phosphine oxide precatalyst for base-free catalytic Wittig reactions has been developed (see scheme). Under the optimized reaction conditions, numerous functionalized alkenes were prepared in yields up to 99 % and with good to excellent E/Z selectivities.

[Full Paper]
Marie-Luis Schirmer, Sven Adomeit, Anke Spannenberg, Thomas Werner
Chem. Eur. J., January 13, 2016, DOI: 10.1002/chem.201503744. Read article.

The First Enantioselective Organocatalytic Synthesis of 3-Spiro-α-Alkylidene-γ-Butyrolactone Oxindoles

The First Enantioselective Organocatalytic Synthesis of 3-Spiro-α-Alkylidene-γ-Butyrolactone Oxindoles

An innovative and flexible methodology catalyzed by bifunctional chiral thioureas was developed to react β-nitro oxindoles with aldehydes (see scheme). This approach allows the first enantioselective synthesis of 3-spiro-α-alkylidene-γ-butyrolactone oxindoles 3 with the aim of merging two potentially bioactive structural motifs: the spirooxindole and the α-alkylidene-γ-butyrolactone.

[Full Paper]
Lucia Cerisoli, Marco Lombardo, Claudio Trombini, Arianna Quintavalla
Chem. Eur. J., January 7, 2016, DOI: 10.1002/chem.201504157. Read article.

Chiral Triazoles in Anion-Binding Catalysis: New Entry to Enantioselective Reissert-Type Reactions

Chiral Triazoles in Anion-Binding Catalysis: New Entry to Enantioselective Reissert-Type Reactions

Against the elements: A family of chiral triazoles has been introduced as innovative C-H bond-based hydrogen donors for anion-binding catalysis. Contrary to the believed inefficiency of the low polarized C-H bonds for promoting organocatalysis, these structures proved to be competitive with respect to the more established N-H-type hydrogen donors in enantioselective Reissert-type reactions.

[Full Paper]
Mercedes Zurro, Sören Asmus, Julia Bamberger, Stephan Beckendorf, Olga García Mancheño
Chem. Eur. J., January 7, 2016, DOI: 10.1002/chem.201504094. Read article.

Acetaldehyde: A Small Organic Molecule with Big Impact on Organocatalytic Reactions

Acetaldehyde: A Small Organic Molecule with Big Impact on Organocatalytic Reactions

Utility of acetaldehyde: Acetaldehyde has recently received a great deal of attention as the simplest enolizable carbonyl compound because of its versatile applications in the synthesis of poly(vinyl alcohol), unnatural amino acids, and medicine (see graphic). This Minireview summarizes a methodologically diverse approach to the synthesis of target molecules by outlining a diverse array of reactions such as aldol, Mannich, Michael, and NHC-catalyzed reactions.

[Minireview]
Sun Min Kim, Young Sug Kim, Dong Wan Kim, Ramon Rios, Jung Woon Yang
Chem. Eur. J., December 15, 2015, DOI: 10.1002/chem.201503960. Read article.

The Resurgence of the Highly Ylidic N-Heterocyclic Olefins as a New Class of Organocatalysts

The Resurgence of the Highly Ylidic N-Heterocyclic Olefins as a New Class of Organocatalysts

One carbon better: N-Heterocyclic olefins, the alkylidene derivatives of the prevalent N-heterocyclic carbenes, have recently emerged as efficient promoters for CO2 fixation and polymerization reactions. Their extraordinarily strong Lewis/Brønsted basicity suggests great potential as a new class of organocatalysts for a broad range of reactions in synthetic chemistry.

[Concept]
Reece D. Crocker, Thanh V. Nguyen
Chem. Eur. J., November 26, 2015, DOI: 10.1002/chem.201503575. Read article.

Whither Organic Synthesis?

Whither Organic Synthesis?

[Review]
Douglass F. Taber
Isr. J. Chem., April 15, 2015, DOI: 10.1002/ijch.201500006. Read article

© Wiley-VCH 2015.