Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• excellent yield and enantioselectivity. Keywords: asymmetric organocatalysis; chiral Brønsted acid; 3,3-difluoroindoline; Hantzsch ester; transfer hydrogenation; Introduction The introduction of fluoro atoms into organic molecules can alter their lipophilicity, solubility, metabolic stability, and

• relatively strict reaction conditions (up to 150 bar H2). In 2022, Liu’s group reported an asymmetric hydrogenation of 3H-indoles catalyzed by a chiral Mn complex, which showed good yield and enantioselectivity [25]. In addition to metal catalysis for the enantioselective reduction, asymmetric

• organocatalysis using chiral phosphoric acids has also been studied (Scheme 1b) [26][27][28]. In 2010, Magnus Rueping and his co-workers developped an enantioselective Brønsted acid-catalyzed transfer hydrogenation of 3H-indoles [29]. In 2020, Song and Yu successfully applied a new chiral Brønsted acid

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• processes are of paramount importance. In particular, the application of asymmetric organocatalysts is receiving increased attention [1][2][3][4]. This is illustrated by the fact that in 2021 the Nobel Prize in Chemistry was awarded for the discovery of asymmetric organocatalysis [5]. The use of

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• acyclic, carbocyclic, heterocyclic, and polycyclic molecular architectures with high molecular complexity. In particular, asymmetric organocatalysis plays a pivotal role in the construction of optically active, bioactive, and natural products. The main advantages of organocatalyzed stereoselective

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• redox-neutral asymmetric organocatalysis, whereas organocatalysis by redox-active molecules stays in the shadows. For example, redox-active organic molecules are almost not mentioned in some recent overviews of compound types used in organocatalysis [3][12][13], except for photoredox catalysts [12][13

• organocatalysis in general. Examples of typical reaction types for redox-neutral asymmetric organocatalysis are aldol reactions [13], Michael reactions [14][15][16], and Diels–Alder reactions [17][18]. The processes associated with changing oxidation states of atoms in substrates thus can be named “redox

• play an important role in redox-neutral asymmetric organocatalysis by forming nucleophilic enamine intermediates or electrophilic iminium cations. The same principles are used in oxidative transformations, where an amine can play the role of chirality source and the activator of substrate for oxidation

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• asymmetric organocatalysis. In order to eliminate the need for C2-symmetry in common CPAs, various scaffolds containing C1-symmetrical thiophosphorus acids were chosen. These new compounds were synthesized and evaluated in the asymmetric transfer hydrogenation of 2-phenylquinoline. Although the efficacy of

• the thiophosphorus acids was disappointing for this reaction, the work should be useful for developing structural design elements. Keywords: asymmetric; heterocycles; organocatalysis; phosphorus; synthesis; Introduction The importance of asymmetric organocatalysis was demonstrated by the 2021 Nobel

• SPINOL [4][5] (Figure 1). The great success of these CPAs in asymmetric organocatalysis, is demonstrated by the publication of thousands of articles and reviews [6][7][8][9][10][11][12][13][14][15][16][17]. In all cases the C2-symmetry is required because of the prototropic tautomeric equilibrium in the

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• Radovan Sebesta Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, 842 15 Bratislava, Slovakia 10.3762/bjoc.18.28 Keywords: asymmetric organocatalysis; covalent activation; noncovalent activation; Asymmetric catalysis is

• organocatalysis edited by one of the pioneers Benjamin List. After another decade, this thematic issue likes to survey new advances in this field. Three review articles and nine research papers showcase the diversity and breadth into which asymmetric organocatalysis has grown since then. The suitability of

• many reactions and a variety of organocatalysts can engage with them [18]. Nine excellent research articles within this special issue demonstrate the current state of the art in asymmetric organocatalysis. Chiral isothioureas became useful Lewis base catalysts for various transformations. Weinzierl and

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• aldehydes and hydrogen-bond activation of nitroalkenes. Keywords: asymmetric organocatalysis; hydrogen bond; Michael addition; pyrrolidine; thiourea; urea; Introduction Asymmetric organocatalysis became one of the strategic ways for the efficient synthesis of chiral compounds [1]. Bifunctional catalysis

• has proven to be a successful concept in asymmetric organocatalysis [2][3][4][5][6][7][8]. An amine unit with a hydrogen-bond donating skeleton is highly efficient from among various possible combinations of catalytic moieties within an organocatalyst. This idea has been inspired by proline catalysis

• /mismatched combination of chirality, we employed both enantiomers of tert-butyl sulfinamide with the (S)-enantiomer of the pyrrolidine building block. The introduction of green chemistry principles into chemical transformations is an important goal toward sustainable production and manufacturing. Asymmetric

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• a specific target, i.e., it gives access to a greater diversity of compounds to be explored [26]. In this work, a compilation of the enantioselective synthesis of coumarin derivatives using asymmetric organocatalysis is presented, highlighting the proposed mechanism pathways for the formation of the

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• no enantioselectivity at all. As arylboronic acids have been harnessed to enhance the Brønsted acidity in asymmetric organocatalysis in combination with chiral diols or chiral aminoalcohols [40][41][42][43][44], we envisioned that the simultaneous use of arylboronic acids and chiral Brønsted acids

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• : asymmetric organocatalysis; axial chirality; biaryls; hydrogen bond; oxo-Diels–Alder reaction; Introduction The Diels–Alder (DA) reaction is a useful and easy-to-perform method for the synthesis of six-membered rings through the direct formation of C–C bonds between a diene and a dienophile (a substituted

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• others [24]. Hence, combining cinchona alkaloids with CDs has the potential to widen the applications of CD derivatives in asymmetric organocatalysis. The combination of cinchona alkaloids with CDs was first reported by Liu et al. [25] who prepared inclusion complexes of cinchona alkaloids and

• alkaloids have never been prepared and tested in asymmetric organocatalysis. Thus, in this study, we investigated methods for attaching cinchona alkaloids to CD skeletons, and we assessed the enantiomeric excess of the resulting CD derivatives as organocatalysts in asymmetric reactions, specifically in the

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• During the past decades, asymmetric organocatalysis has played an important role as a tool for the syntheses of chiral molecules under mild conditions [1][2][3][4]. Among these reactions, the asymmetric Michael reaction is a powerful strategy to construct versatile intermediates due to its synthetic

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• rim have been successfully developed and used in chiral recognition. But their use in asymmetric organocatalysis hasn’t been reported. To explore the organocatalytic behaviors of inherently chiral calix[4]arenes modified at the lower rim, Li et al. reported the synthesis of N,O-type enantiomers based

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• provide 3-substituted isoindolinones in good yields and diastereomeric excesses. This methodology was applied to the asymmetric synthesis of a new pazinaclone analogue which is of interest in the field of benzodiazepine-receptor agonists. Keywords: asymmetric organocatalysis; Aza-Michael reaction; phase

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• catalyst. Furthermore, specific organocatalysts can provide respective stereoisomers of the key Michael adduct in up to 99:1 er. Keywords: kinetic resolution; Michael addition; organocatalysis; pregabalin; squaramide; Introduction Asymmetric organocatalysis has considerably broadened possibilities for

• amino acids have also been investigated as treatments for ocular disorders [7]. However, the syntheses of this type of compounds were long and relied on the use of Evans chiral auxiliaries or chiral starting materials. Various GABA derivatives were synthesized using asymmetric organocatalysis

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• strategy. Hereby both, approaches relying on either asymmetric metal- or organocatalysis, have been well-investigated already [105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122]. In the field of non-covalent asymmetric organocatalysis, chiral H-bonding catalysis [37

• -transfer reactions is hydrogen peroxide (H2O2). Unfortunately, the direct use of this base-chemical under asymmetric organocatalysis turned out to be rather tricky for α-hydroxylation reactions. One recent report by the Ooi group overcame some of the limitations by using H2O2 in combination with

Copper-catalyzed asymmetric sp³ C–H arylation of tetrahydroisoquinoline mediated by a visible light photoredox catalyst

• Pierre Querard,
• Inna Perepichka,
• Eli Zysman-Colman and
• Chao-Jun Li

Beilstein J. Org. Chem. 2016, 12, 2636–2643, doi:10.3762/bjoc.12.260

• of THIQs with arylboronic esters via asymmetric organocatalysis methodology [25][28]. The use of chiral tartaric acid derivatives, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and high temperature (70 °C) were found to be the optimal conditions to obtain the desired arylated product with

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• ) were obtained for a series of spirocyclic 1,4-sulfur-bridged piperidinone-based succinimides. Keywords: [4 + 2] annulation; asymmetric organocatalysis; dipeptide-based Brønsted bases; 5H-thiazol-4-ones; N-itaconimides; Introduction Sulfur-containing tetrasubstituted carbon stereocenters are widely

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• have been developed and used in the synthesis of natural products and pharmaceutical agents. Biologically important 3-hydroxyoxindoles with a chiral quaternary center at the 3-position have been successfully accessed utilizing the asymmetric organocatalysis in the last few years. To show recent

Asymmetric α-amination of 3-substituted oxindoles using chiral bifunctional phosphine catalysts

• Qiao-Wen Jin,
• Zhuo Chai,
• You-Ming Huang,
• Gang Zou and
• Gang Zhao

Beilstein J. Org. Chem. 2016, 12, 725–731, doi:10.3762/bjoc.12.72

• tetrasubstituted carbon center have been recognized as core building blocks for the preparation of many biologically active and therapeutic compounds [2][3][4][5][6][7]. As a type of commercially available electrophilic amination reagents, azodicarboxylates have been extensively used in both asymmetric

• organocatalysis and metal catalysis for the construction of this type of structures. For example, Chen et al. reported the first organocatalytic enantioselective amination reaction of 2-oxindoles catalyzed by biscinchona alkaloid catalysts [8]. Zhou [9][10] and Barbas [11][12], have independently reported similar

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• trifluoroethylamine moiety [3][4][5]. However, it is in the field of asymmetric organocatalysis [6][7][8] where the aminoindanol core has gained more importance, being a recurrent structural motif in several organocatalytic species. Some examples are (a) the enantioselective reduction of ketones through the in situ

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• asymmetric organocatalysis. This fascinating class of bifunctional catalyst offers a genuine alternative to the more commonly used thiourea systems and because of the different spacing between the functional groups, can control enantioselectivity where other organocatalysts have failed. In the main, this

• their derivatives in asymmetric organocatalysis over the last five years or so [13][14]. The review is organized by reaction type, beginning with the Morita–Baylis–Hillman process – one of the first reactions to utilize 6’-OH-cinchona alkaloid derivatives in asymmetric organocatalysis. The focus will

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• -pyrrol-2(3H)-ones bearing quaternary stereocenters were obtained in acceptable yield (up to 75%) and enantioselectivity (up to 73% ee). Keywords: asymmetric catalysis; bifunctional catalysts; Henry reaction; organocatalysis; 1H-pyrrole-2,3-diones; Introduction Asymmetric organocatalysis has been

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• support in asymmetric organocatalysis. The use of chiral imidazolidinones in organocatalysis has been extensively reported for a wide range of enantioselective reactions involving α,β-unsaturated aldehydes, such as the Diels–Alder reactions [50], 1,3-dipolar cycloadditions [51] and Friedel–Crafts

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• asymmetric organocatalysis In the previous section, the developmental history of acidic acylation methodologies for chemoselective O-acylation of hydroxyamino acids has been chronicled, from its inception in the early 1940s until the 1990s. In particular, the identification and application of suitable

• asymmetric organocatalysis picked up momentum quite rapidly. Through a series of disclosures, during the time period from 2010 to 2012, Xiangkai Fu and co-workers detailed the preparation of amphiphilic organocatalysts from serine, threonine and cysteine by acidic O-acylation, as well as their use in

• asymmetric organocatalysis [54][55][56][57][58][59][60][61]. Chemoselective O-acylation of serine, threonine and cysteine in CF3CO2H with a range of acyl chlorides, followed by crystallization of the product directly from the reaction mixture by addition of Et2O, furnished a comprehensive collection of