Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• -proline-modified magnetic nanoparticles (LPMNPs) that combine organocatalytic protocols with nanocatalysis, which enhances the surface-to-volume ratio of the catalyst opening up new possibilities [107]. The ʟ-proline molecules were anchored on a Fe3O4@SiO2 nanoparticle, which was already known for its

• facile recyclability, with the silica layer preventing the Fe3O4 from aggregation. The LPMNPs managed to provide impressive yields, while employing an amount of 2.5 mol % in water, with the help of conventional heating at 50 °C, which facilitated the organocatalytic process that required 1 to 1.5 hours

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• there might be more to win before the electrons jump. Being general and easy to use, the introduced supramolecular organocatalytic systems promise to lift all involved topics to a new level of significance. Essentially every reaction consists of the movement of electrons, from nucleophile to

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

• Budapest, Hungary 10.3762/bjoc.19.133 Abstract Synthesizing organocatalysts is often a long and cost-intensive process, therefore, the recovery and reuse of the catalysts are particularly important to establish sustainable organocatalytic transformations. In this work, we demonstrate the synthesis

• time was increased to 5 hours to achieve full conversion. After the organocatalytic reaction in toluene, the volatile components were evaporated, and acetonitrile was added to precipitate the catalyst. In contrast to the small-scale recycling, in this case, we used filtration instead of centrifugation

• to recover the catalyst without significant loss (<5%). This demonstrates that we developed an organocatalytic reaction that can be easily scaled-up and the novel lipophilic catalyst can be recovered not only by centrifugation but also by filtration. From the baclofen precursor (S)-17, baclofen can

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• pairs and provides a good basis and scope for further extensions and explorations [39] (Scheme 3). Based on the work by Wu et al. and extending their previous work, Rueping and co-workers explored the effects of fluorine in organocatalytic reactions. They developed an asymmetric Brønsted acid–Lewis base

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• and Cheng et al. developed a convenient approach for the thiolation of β-keto phosphonates 89 by using N-(arylthio)phthalimides 14 under α,α-diaryl-ʟ-prolinols B organocatalytic system (Scheme 37) [71]. Sulfenylation of 3-aryloxindoles 91 with N-(arylsulfenyl)phthalimides 14 as the electrophilic

• thiophosphates, thiophosphinates and selenophosphates by reaction with the P(O)H moieties of H-phosphonates [105]. Conclusion To date, both metal-catalyzed and organocatalyzed C–S bond formations have been widely expanded. In particular, organocatalytic methodologies are effective for direct construction of

• conjugate Lewis base Brønsted acid catalyst. Sulfenylation of deconjugated butyrolactams. Intramolecular sulfenofunctionalization of alkenes with phenols. Organocatalytic 1,3-difunctionalizations of Morita–Baylis–Hillman carbonates. Organocatalytic sulfenylation of β‑naphthols. Acid-promoted

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• single operation and from readily available substrates. Their combination with asymmetric aminocatalysis [4][6][7][8] has recently led to innovative approaches for the one-step enantioselective preparation of stereochemically dense molecules. Nowadays, organocatalytic cascade processes provide a powerful

• organocatalytic cascade reaction developed by Enders. Acetaldehyde dimethyl acetal (6) as an acetaldehyde surrogate to effect a triple organocatalytic cascade reaction. Enders reaction with acetaldehyde.a Selected optimization reaction conditions.a Supporting Information Supporting Information File 34

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• simultaneous organocatalytic activation of the ester on the other hand. Following a previously established synthetic pathway [49], we have found that transmetallation via silver(I)/NHC complex 4 was the only viable synthetic entry point to this sophisticated bifunctional catalyst (Scheme 2) [10][12][14][50

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• amorph-4-ene-10β-ol known from plants. A short synthesis using an organocatalytic approach through a tandem Mannich/intramolecular Diels–Alder reaction led to a mixture of cadinols, which was used for the assignment of the natural cadinol structures and their stereoisomers. Keywords: Anura; chiral gas

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• enantioselective organocatalytic aza-Nazarov cyclization affording six-membered heterocycles after a ring expansion of the cyclization products [22]. Rasapalli and co-workers recently developed an efficient aza-Nazarov cyclization of quinazolinonyl enones promoted by TfOH or MsOH (methanesulfonic acid) for the

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• synthetic route based on a convergent strategy to accomplish the synthesis of principinol E, grayanotoxin III and rhodomollein XX [34]. The key steps include i) a tandem reaction combining organocatalytic Mukaiyama aldol and intramolecular Hosomi–Sakurai reactions in a one-pot manner; ii) a 7-membered

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• organocatalytic units embedded in polymers for catalysis in small molecule systems have been discussed [15][19][20]. Moreover, the ability of force to deform the reaction energy landscape and modulate the reversibility of the reactions within proteins has been demonstrated. For example, mechanical force was used

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

• cavity could resemble the circumstance of the catalytic triad of Polyketide synthases (PKSs) [40][41][42] (Figure 1). On the other hand, the organocatalytic asymmetric decarboxylative addition reactions of MAHTs to imines provide an efficient means for accessing valuable chiral β-amino esters [43][44][45

New advances in asymmetric organocatalysis

• Radovan Šebesta

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

• within the area. Organocatalytic reactions are highly suitable components of cascade transformations as exemplified by the seminal work of Enders [13]. Besides traditional enamine and iminium activation of carbonyl compounds other activation modes were uncovered which significantly broadened the

• asymmetric organocatalytic methods to assemble biologically relevant compounds is highlighted by a review article devoted to the syntheses of coumarin derivatives [16]. Conjugated additions of stabilized nucleophiles are the cornerstone of organocatalytic methodology. Recent advances in this area are covered

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• takes place to afford the nitroso aldol product. Conclusion In summary, an efficient organocatalytic asymmetric nitroso aldol reaction of α-methylmalonamate has been reported. The reaction utilizes the well-known Takemoto catalyst, and this protocol demonstrates for the first time the use of malonamate

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• molecular complexity. There are many examples of the organocatalytic synthesis of fused cycles starting from the cyclohexane-1,3-dione. For example, Rueping et al. demonstrated that the cyclohexane-1,3-dione undergoes a cascade reaction with α,β-unsaturated aldehydes [4] and they later employed the method

• using CPD as a precursor for high value-added fine chemicals such as a homocitric acid lactone was published by our group [19]. Since then we have developed synthetic pathways for lycoperdic acid [20] and nucleoside analogues [21] starting from CPD. The organocatalytic methods for the synthesis of

• malonates [25]. Herein, we report the results of an asymmetric organocatalytic Michael addition of CPD to alkylidene oxindoles. Results and Discussion Chiral multifunctional thioureas [26][27] and squaramides [28] are extensively used as catalysts in asymmetric Michael additions. We believed that a

Chemoselective N-acylation of indoles using thioesters as acyl source

• Tianri Du,
• Xiangmu Wei,
• Honghong Xu,
• Xin Zhang,
• Ruiru Fang,
• Zheng Yuan,
• Zhi Liang and
• Yahui Li

Beilstein J. Org. Chem. 2022, 18, 89–94, doi:10.3762/bjoc.18.9

• of the N(sp2)–H bond by using a catalytic amount of DBU for the preparation of indoleamides [14] (Scheme 1, A2). Subsequently, Sundén reported an efficient chemoselective method for the synthesis of indoleamide by oxidative organocatalytic reaction of indole derivatives and conjugated aldehydes under

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• strategy to construct a series of spirobarbiturates derived from indanone. Combining current researches of these two compounds, we report the first organocatalytic asymmetric Michael addition/cyclization reaction between barbituric acid-derived olefins and indanones (Scheme 1b). Under the action of the

• organocatalytic domino Michael/cyclization reaction. This annulation reaction can be easily performed under air atmosphere and mild conditions with 5 mol % catalyst loading. By using bifunctional thiourea catalyst, a series of structurally diverse indanone-derived spirobarbiturates could be obtained in high

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• the proline catalysis are of higher purity (after purification by silica gel column chromatography), than those synthesized by other methods [16]. Definitely, the effective asymmetric organocatalytic conjugate additions of hydroxylamines to enals using various catalysts provide access to

• racemic codonopsinol B (1) and its N-nor-methyl analogue 2 starting from achiral materials. Four consecutive stereocenters in the target molecules were accomplished sequentially by the organocatalytic aza-Michael addition of N-Cbz-protected hydroxylamine to (E)-4-methoxycinnamaldehyde, the trans

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• functional calculations showed that the chiral phosphoric acid proton forms an H-bond with nitrogen atoms of 1 and the phosphate acts as a chiral counterion, resulting in a [3,3]-sigmatropic rearrangement with controlled stereoselectivity [14][41]. In 2017, Tan and co-workers developed an organocatalytic

• ]. Organocatalytic aryl C–H activation via a nonradical process represents an enormous challenge in organic synthesis, although the nucleophilic aromatic substitution with cleavage of the electrophilic aryl C–H bond has only recently been developed by transition-metal-catalyzed aryl C–H activation [57]. In the

• -workers showed that azo groups enable the organocatalytic asymmetric arylation of indoles. The nucleophilic aromatic substitution between the azobenzene derivative 24 and indoles 25 was carried out in the presence of 2.5 mol % chiral phosphoric acid (CPA 8, Scheme 9a), leading to the intermediate I-4

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• -nitrosilanes through a Cu(II)–chiral bipyridine complex catalyzed enantioselective silyl transfer reaction to nitroalkenes using Suginome’s silylboron reagent (Scheme 1a) [28]. Recently, we have reported the synthesis of chiral β-nitrosilanes via an organocatalytic conjugate addition of nitromethane to β

• nucleophiles to β-silyl α,β-unsaturated carbonyl compounds were documented as one of the straightforward and atom-economic approaches for the facile synthesis of chiral organosilanes (Scheme 1c–f) [30][31][32][33]. Recently, the aforementioned reaction under organocatalytic conditions has gained attention [34

• to moisture and air. Therefore, this method offers an attractive and robust option for the preparation of chiral β-silyl nitroalkanes. In sharp contrast to the aforesaid reaction, organocatalytic conjugate addition reactions of nitroalkanes to enones have been well studied [39][40][41][42][43]. To

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

• organocatalytic transformations were successfully performed under solvent-free ball-milling conditions [30][31]. In this context, we describe the synthesis of new pyrrolidine appended sulfinylurea and thiourea organocatalysts and their assessment in Michael additions of aldehydes to nitroalkenes. Furthermore, we

• of the catalysts in organocatalytic Michael addition and suggested the possibilities of further improvement in catalyst design. Experimental Synthesis of catalysts (S)-tert-Butyl 2-(aminomethyl)pyrrolidine-1-carboxylate (2) The solution of PPh3 (1.64 g, 6.3 mmol) and N-Boc-(S)-prolinol (1, 1.0 g, 5.0

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• be accessed from the chiral pool. Both types of organocatalysts, namely those acting through non-covalent bonding as well as those working by making covalent bonding have been employed for accomplishing asymmetric aza-MRs. There are several review articles available on organocatalytic asymmetric aza

• . Review In the present review, the known stereoselective syntheses of pharmacology-oriented nitrogen containing heterocyclic scaffolds via non-covalent bonding and covalent bonding organocatalytic aza-MRs has been systematized. This classification is especially useful for researchers to understand both

• compounds; however, in order to comply with the requirements of a mini review, additions of amines and amides only will be included. 1. Non-covalent bonding organocatalytic aza-Michael reactions Organocatalysts catalyzing aza-MRs through mainly hydrogen bonding include cinchona alkaloids, squaramide

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• organocatalytic synthesis of molecules with this moiety uses the reaction between aldehydes and anthranilamide building blocks. The advantage of this methodology lies in the fact that both starting materials are readily available, and the enantioselectivity of such cyclization reactions can be controlled by

• configuration of aminals obtained by List and co-workers [14]. Conclusion In summary, we have reported an organocatalytic asymmetric aminalization reaction between aldehydes and anthranilamides catalyzed by a PCCP catalyst as a cheap and readily available option to conventional chiral BINOL phosphoric acids

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

• electrophilic and nucleophilic α-functionalizations are possible, whereas with the use of α,β-unsaturated aldehydes the β-position is functionalized with nucleophiles and the γ-position with electrophiles. In this sense, Jørgensen and colleagues have developed the first organocatalytic asymmetric Michael

• acid (4) as catalyst [30]. Based on this pioneer work, our research group described an efficient, highly stereoselective, one-pot process comprising an organocatalytic conjugate addition of dimedone or 4-hydroxycoumarin 1 to α,β-unsaturated aldehydes 2 followed by an intramolecular isocyanide-based

• the desired transformation by using only one catalyst [70]. In this sense, an efficient asymmetric organocatalytic reaction was reported by Zhang et al. for the synthesis of 2,8-dioxabicyclo[3.3.1]nonanes [71]. A combination of catalysts 7 and 110, involving iminium and anion-binding catalysis

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• Chandrakanta Parida Subhas Chandra Pan Department of Chemistry, Indian Institute of Technology Guwahati, North Guwahati, Assam, 781039, India 10.3762/bjoc.17.100 Abstract An organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones is

• -nitroketones have been found to be a popular nucleophilic acyl transfer reagent. In 2011, three research groups namely Wang, Yan and Kwong independently revealed the organocatalytic asymmetric conjugate addition of α-nitroketones to β,γ-unsaturated α-keto esters with the concomitant acyl transfer reaction to

• the keto group [11][12][13]. Consequently, our group developed an organocatalytic asymmetric Michael–acyl transfer reaction of α-nitroketones with unsaturated pyrazolones, 2-hydroxycinnamaldehydes, γ/δ-hydroxyenones, o-quinone methides, etc. [14][15][16][17][18]. Other groups also contributed