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

• organocatalysts is well-established in several organic reactions, including but not limited to aldol reactions [6], Michael additions [9], Mannich reactions [10], aza-Henry reactions [11], and Diels–Alder cycloadditions [12][13]. Although the benefits of organocatalysts are undoubted, their synthesis is often a

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• electrophilic iminium carbon, leading to the amine product as racemic mixture. Consequently, examples for asymmetric Petasis borono-Mannich reactions are rare [13] and usually rely on the utilization of chiral amine components in stoichiometric amounts [10][11]. As part of our research program utilizing the in

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• tetraaminobisthiourea chiral macrocycles as catalysts in decarboxylative Mannich reactions. Low macrocycle loading was used to catalyze the decarboxylative addition of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. It was reported that effective activation

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• intermediates in the total synthesis of natural products utilizing their electrophilic keto group as reactive site. Suitable key reactions are, e.g., aldol additions, carbonyl ene reactions, Mannich reactions, and additions of organometallic reagents. The vicinal arrangement of carbonyl groups allows the

• bearing an electrophilic keto group as reactive site. The vicinal arrangement of carbonyl groups allows the stabilization of reactive conformations by chelation or dipole control. Suitable key reactions are e.g., aldol additions, carbonyl ene reactions, Mannich reactions, and additions of organometallic

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• readily incorporated by both homo and hetero [1 + 1] macrocyclic condensation of bisamine and bisisothiocyanate fragments. With the easy synthesis, gram-scale of macrocycle products can be readily obtained. These chiral macrocycles were applied in catalyzing bioinspired decarboxylative Mannich reactions

• Mannich reactions; supramolecular catalysis; thiourea; Introduction In the past decades, the development of supramolecular chemistry has enabled abundant host scaffolds and assembly tools for boosting catalytic processes, and stimulated the emergence of supramolecular catalysis [1][2][3][4][5][6][7][8][9

New advances in asymmetric organocatalysis

• Radovan Šebesta

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

• disclosed important discoveries with proline and imidazolidinones as ample chiral catalysts for aldol [7][8], Diels–Alder [9], dipolar cycloaddition [10], and Mannich reactions [11]. The organic chemistry community this time took a tremendous interest in this concept, which led to many valuable developments

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• the synthesis of a limited range of SMAHOs, presenting little diversity. Within the framework of a project pertaining to the use of SMAHOs in Galat [54] and Mannich reactions [55], we were confronted with a lack of pertinent bibliographical information, which led us to investigate the few reported

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• -ethoxycarbonyl derivative [43], two reactions dating from 1917 and also based on iterative intramolecular Mannich reactions. Guareschi supported a distinction between scientific and industrial developments and claimed that, unlike many colleagues from the rest of Europe, who had accumulated great fortunes thanks

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• yne nucleophiles have never been reported thus far. Accordingly, intrigued by this methodological deficiency, we decided to dedicate a special research project to this objective; herein, we report Mannich reactions between yne nucleophiles and aldimine 1 (Scheme 1c). The results reported in this work

• optimized reaction conditions in hand, we examined the generality of these asymmetric Mannich reactions by using various arylethynes 2 (Scheme 2). Under standard reaction conditions, all the tested substrates worked well to generate the corresponding Mannich adducts in moderate to good yields. In particular

• conditions and the target primary amine 4 was obtained with 57% yield. Conclusion In conclusion, we have explored arylethynes as new nucleophiles for the Mannich reactions of (R)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine. Quite unexpectedly, the diastereoselectivity of the reactions were noticeably

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• nitrosation (with sodium nitrite in acetic acid), and in Mannich reactions [12]. For the formation of dimers 5, various mechanisms were envisaged. Nevertheless, the formation of any dimer-like product structurally similar to 3a has not been observed so far. In this report we describe our efforts to extend the

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• -aryltetrahydroisoquinoline, ketones, and ʟ-proline using a low PdTPFPP loading (Scheme 62) [97]. Zhang and co-workers demonstrated that the MOF-catalyst (UNLPF-12) can also be used for the Mannich reactions. The authors reported that the coupling between N-aryltetrahydroisoquinolines and acetone using visible light and

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• reactions, Ugi–Smiles reactions, Mizoroki–Heck reactions, aldol reactions, oxidation and dehydration reactions, Mannich reactions, and multicomponent reactions. Because of the mentioned reasons as well as due to the low toxicity of silica nanoparticles, they are often a good option [24]. For this review

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• additions to isatin imines have been developed, including Mannich reactions, aza-Morita–Baylis–Hillman reactions, Friedel–Crafts reactions, aza-Henry reactions, additions of heteronucleophiles, Strecker reactions, among others. The goal of this review is to update the catalytic asymmetric synthesis of

• chiral 3-substituted 3-amino-2-oxindoles based on enantioselective nucleophilic additions to isatin imines reported since 2015, since this field was recently reviewed by Chimni et al. [16]. It is divided into six parts, dealing successively with enantioselective Mannich reactions, aza-Morita–Baylis

• also proved to be highly efficient for a range of transformations. Review Enantioselective Mannich reactions Organocatalyzed reactions Originally, the Mannich reaction is a three-component process occurring between an aldehyde, an amine and a ketone, providing β-amino carbonyl compounds [23][24][25

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• Mannich reactions where the process involves an ortho-quinone methide (o-QM) intermediate. The reactions are classified on the basis of the o-QM source followed by the reactant, e.g., the dienophile partner in cycloaddition reactions (C=C or C=N dienophiles) or by the formation of multicomponent Mannich

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• , Nakanarusawa 4-12-1, Hitachi 316-8511, Japan 10.3762/bjoc.13.244 Abstract As an extension of the boron enolate-based aldol reactions, the oxazolidinone-installed bisimide 1a from 3-(trifluoromethyl)glutaric acid was employed for Mannich reactions with tosylated imines 2 as electrophiles to successfully obtain

• the corresponding adducts in a stereoselective manner. Keywords: chiral oxazolidinones; diastereoselectivity; Mannich reactions; pseudo-C2 symmetry; trifluoromethyl; Introduction During these decades, we have been keenly interested in the 3-(trifluoromethyl)glutaric acid derivatives and developed a

• , based on its inherent pseudo-C2 symmetric structure [6][7][8] which enables the formation of plural stereogenic centers by a single operation. These promising results prompted us to extend this aldol protocol to its relative, Mannich reactions [9][10][11][12][13] whose details are reported in this

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

• C–C bond forming reactions like, e.g., α-alkylations, Michael additions, Mannich reactions, or aldol reactions, to mention the most prominent examples only, also asymmetric α-heterofunctionalizations like hydroxylations, halogenations, or aminations have become increasingly important over the last

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• attributed to their ability to form a hydrogen bond with the oxygen of epoxide. In 2015 Shirakawa and Maruoka demonstrated that ammonium salts L5 and L6 could serve as effective catalysts for isoquinolinium and pyridinium salt Mannich reactions (Scheme 7) [50]. Catalysts L5 and L6 were selected due to their

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• their Lewis acidity. Cationic palladium complexes [123], in particular, possess a wide breadth of reactivity, having been used to catalyze Diels–Alder [124][125], aldol and Mannich reactions [126][127][128], Wacker oxidations [129], polymerizations of alkenes [130][131], and asymmetric 1,4-additions

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• -additions to allenic ketones and esters [35][36], 1,6-additions to conjugated dienones [37], aldol/Mannich reactions [26][38][39][40], α-sulfenylation reactions [41] and alkylations [42][43]. More recently the nitrogen (1H-imidazol-4(5H)-ones, Figure 1b, X = NR’) and sulfur (thiazol-4(5H)-ones, Figure 1b, X

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

• successfully used as chiral organocatalysts for the asymmetric Michael addition and Mannich reactions [12][13][14]. Meanwhile, the Henry reaction is one of the most important carbon–carbon bond-forming reactions that provides straightforward access to β-nitroalcohols, which can be further transformed into

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

• ]. The amphiphilic organocatalysts, often referred to as hydroxyamino acid (serine or threonine) surfactant organocatalysts by the authors, were then applied with success in asymmetric anti-Mannich reactions and asymmetric aldol reactions of ketones and aromatic aldehydes, in the presence of water [54

• -component Mannich reactions under aqueous conditions [65][66][67]. Use of chemoselective O-acylation of hydroxyproline for preparation of polymeric organocatalysts The last couple of years have witnessed an interesting proliferation in the use of chemoselective O-acylation of hydroxyproline with acrylic

Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

• Xacobe C. Cambeiro,
• Rafael Martín-Rapún,
• Pedro O. Miranda,
• Sonia Sayalero,
• Esther Alza,
• Patricia Llanes and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2011, 7, 1486–1493, doi:10.3762/bjoc.7.172

• catalyst for the direct enantioselective aldol [41] and Mannich reactions [42] as well as for the α-aminoxylation of carbonyl compounds under batch conditions [43]. Interestingly, the triazole linker between the polymer and the active unit, inherently resulting from the Cu(I)-catalyzed cycloaddition of

PEG-embedded KBr₃: A recyclable catalyst for multicomponent coupling reaction for the efficient synthesis of functionalized piperidines

• Sanny Verma,
• Suman L. Jain and
• Bir Sain

Beilstein J. Org. Chem. 2011, 7, 1334–1341, doi:10.3762/bjoc.7.157

• –Alder reactions [22][23], intramolecular Michael reactions [24], intramolecular Mannich reactions onto iminium ions [25], tandem cyclopropane ring-opening/Conia-ene cyclizations [26], and aza-Prins-cyclization [27][28][29], have been reported for the synthesis of piperidines. However, these methods

Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.0^2,6]decane skeleton

• Matthias Breuning,
• Tobias Häuser,
• Christian Mehler,
• Christian Däschlein,
• Carsten Strohmann,
• Andreas Oechsner and
• Holger Braunschweig

Beilstein J. Org. Chem. 2009, 5, No. 81, doi:10.3762/bjoc.5.81

• (five steps). The required endo-orientation of the acetic acid moiety in 8a•HCl was confirmed by the X-ray structure of the corresponding free base 8a•MeOH (Figure 4). A first evaluation of the bowl-shaped amino acid derivatives 7 and 8 in standard organocatalytic aldol and Mannich reactions showed that

• at a more remote position of the molecule, but still in close spatial proximity to the amino function. Examples are β-proline (4) [18][19], the bispidinium salt 5 [20], and the binaphthyl-derived amino acid 6 [21][22][23], which provided excellent enantioselectivities in several aldol and Mannich

• reactions. Our studies targeted the chiral, tricyclic amino acid derivatives 7 and 8 (Figure 2), which possess a central norbornane framework equipped with a 2-endo,3-endo-annelated pyrrolidine ring. Due to the constrained, bowl-shaped backbone, these compounds may possess high potential as β-turn-inducing