Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• optimization algorithm allowed them to discover multiple trade-off optima, enabling a scientist to select the ideal catalyst based on the specific requirements of catalytic activity and selectivity, while still accounting for catalyst generality through design of the objectives. Noticeably, data analysis

• witnessed a surge in data-driven approaches to improve the design of reactions, e.g., by inferring mechanistic features through statistical modelling, the generation of catalyst structures with increased catalytic activity, or optimising the reaction conditions to maximise the yield or selectivity. In

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• , including the type of support, immobilisation techniques and the resulting interactions. In addition, the influence of these factors on catalytic activity, selectivity and recyclability is discussed, providing an insight into optimising the performance of immobilised organocatalysts for practical

• reaction components and the catalyst are in the same phase. Active catalytic sites are readily accessible to the reactants and therefore generally result in higher catalytic activity and selectivity [8]. As a result, homogeneous catalysis is generally preferred to heterogeneous catalysis, especially in the

• influence on the properties and thus performance of the resulting heterogeneous catalyst. However, immobilisation and structural modification introduce additional steps in the synthesis of the catalyst. Moreover, the catalytic activity and selectivity of immobilised catalysts are often lower than those of

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• tumor bed of a vast diversity of human tumor types. As phenylalanine is the preferred substrate of IL4I1 catalytic activity, Presset et al. [6] reported novel phenylalanine derivatives as a strategy to inhibit IL4I1 activity, as this enzyme has a preference for hydrophobic amino acids. Among them

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• conditions can also be found. 1.1 Metal and Brønsted acid catalysts As previously mentioned, Sc triflate is the most widely used Lewis acid for the GBB reaction, generally exhibiting higher catalytic activity compared to other metal triflates, such as Yb, In or Bi. No extensive work had been done on rare

• catalysts Noncovalent organocatalysts display a few advantages compared to the traditional metal Lewis acids, such as lower environmental impact, higher stability to air and moisture, easier removal from the GBB products. In this regard, Bolotin et al. in 2022 have reported the high catalytic activity of

• an effective chalcogen bond donation to the substrates, in place of the halogen bonding previously described. Although their catalytic activity was reported to be lower than the one of aryl iodonium derivatives, this research contributed to the scarce number of publications on the catalytic activity

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• domain from the clostrisin cluster). The latter contains the peptidase domain of CloPt1, as the complete ABC transporter was deemed too large to synthesize and express in this system. This strategy was functional in previous studies and retained catalytic activity without the rest of the transporter

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• surfactants. Structural analysis and site-directed mutagenesis identified residues important for the catalytic activity of ChSase B6 [60]. In addition, a novel laminarinase, MaLamNA, was characterized and expressed in Pichia pastoris from the same bacterium. It functioned exclusively towards the substrate

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

• substitution patterns on the redox catalytic activity. Keywords: cross-dehydrogenative coupling; O2 activation; phenotellurazine; redox catalysis; Te catalysis; Introduction Tellurium catalysis has become increasingly important in recent years. This is due to its unique chalcogen bonding ability, thus

• in the structure, or else at different positions, in order to establish how their redox catalytic reactivity might be affected. Indeed, we learned recently that amino-arenes possess some level of redox catalytic activity by themselves, in the absence of a Te-center [34], and therefore wished to

• diverse electron-donating or -withdrawing functional groups all featured significantly inferior catalytic activity in the selected benchmark reaction (O2-mediated dehydrogenative phenothiazination of 4-phenylphenol). It can therefore be deduced that the N-bridging atom is important for catalytic activity

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• contraction reactions, yielding a benzofluorene intermediate 4 and the dimer 5, both featuring a kinamycin skeleton (Scheme 1) [11][12]. Recent investigations unveiled the catalytic activity of the O-methyltransferase-like protein AlpH, which catalyzes a unique SAM-independent coupling of ʟ-glutamylhydrazine

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• partially localised in the nucleus of cells and, in cancer cells, become genotoxic [24]. A3A and A3H are single-domain enzymes, whereas A3B is a double-domain enzyme, in which only the C-terminal domain (CTD) has catalytic activity, and the N-terminal domain (NTD) is responsible for binding of DNA and for

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• supply, overexpressing PsBCH-CsCCD2, and optimizing the fermentation medium, the yield of crocetin (1) reached 12.43 ± 0.62 mg/L in a 5 L bioreactor [115]. While CCD has a higher catalytic activity at low temperature, the biosynthesis of zeaxanthin (7) is more suited to a higher temperature. As such, Liu

• , and UGTs are the key players in crocin biosynthesis. Empowered by the genomic, transcriptomic, and metabolomic analysis and biochemical characterization, many such enzymes have been identified. Some proteins, exemplified by GjCCD4a and GjUGT94E13, exhibit broad substrate promiscuity and high catalytic

• activity. Screening of novel enzymes for crocin biosynthesis and the directed evolution of known enzymes should facilitate the high-titer production of the key intermediates 5–7 etc. and the efficient conversion of these precursors into crocetin (1) and crocins. In conclusion, crocins are high-value plant

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• based on derivatives of imidazolidin-4-one were synthesised and characterised. The catalytic activity and enantioselectivity of their corresponding copper(II) complexes were studied in asymmetric Henry reactions. It was found that the enantioselectivity of these catalysts is overall very high and

• donor ability to pyridine. This change reduces the ring size within the ligand structure, potentially increasing the space available for coordinating reacting species, thereby possibly enhancing catalytic activity and enantioselectivity. We also aimed to assess the impact of alkyl groups at the 5

• (i.e., temperature, reaction time, amount of catalyst, solvent) were adopted from the pilot study [5] for relevant comparison of catalyst characteristics. From Table 1 and Table 2, which summarise results obtained using tridentate ligands Ia–c and IIa–c, it is evident that the catalytic activity their

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• tweezers 16 were then synthetized by Vives and co-workers using a 6,6”-substituted terpyridine this time bearing zinc(II)–salphen complexes [47]. The catalytic activity was evaluated in an acetyl transfer reaction between pyridinemethanol derivatives and anhydrides. For the ortho derivative, a rate

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• were shown to proceed with anti-selectivity and that was used as support for gold catalysis [15], but mechanism studies of triflic acid catalysis showed a preference for anti-selectivity as well [31]. Despite similarities, control studies indicate meaningful differences in catalytic activity between

• generally acidic conditions that initiate cyclization [34][35]. These observations are critical for informing future discussion and experiments related to this important reaction. Results Ligand effect To examine the catalytic activity of gold with ligands of different electronic properties, we used our

• concerted attack and protonation [59]) may be being mimicked by the gold-catalyzed processes here, further supporting the viability of a mechanism like that shown in Scheme 2. Finally, at its extreme, increasing nitrogen basicity inhibits gold catalytic activity, but within this low basicity regime, the

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

• counterparts, due to their recyclability, ease of handling, and low cost [40]. Carbon-based solid acid catalysts especially are an interesting catalyst class, because they display low corrosiveness, toxicity, and higher catalytic activity, while also being insoluble in most organic solvents. The large amount

• reaction of aldehydes and ketones with indole [93][94]. Bidentate halogen-bond donors are efficient catalysts, since they can form two halogen bonds with each substrate, instead of just one. Thus, compounds 24, 25 and 26 were screened for their catalytic activity with 26 emerging as the optimum choice

• 100 nm, exhibit various benefits, such as tailoring the scaffold of the catalyst, the recyclability of the nanocompounds, as well as the elevated catalytic activity offered. These benefits stem from their high surface area, that provides more active sites for the reactants to absorb into and collide

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• -coumaric acid via diazotization-dependent deamination. The diazotase CmaA6 had a high catalytic activity, which enabled us to determine the kinetics of the denitrification reaction catalyzed by AvaA7. Furthermore, careful comparison between ava and cma clusters provided insights into (i) the mechanism of

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

• fullerenes as well. The unique polarizability of fullerene monomers like 1 is thought to induce strong anion–π interactions and thus account for the observed catalytic activity (Figure 7A) [12]. This polarizability should further increase in fullerene dimers like 36 [80]. Anions, anionic reactive

• activity did not originate from a change in intrinsic anion–π interactions. The computed polarizability of dimer 37 (α = 1499 a.u.) was almost twice as high as that of monomer 22 (α = 903 a.u.), confirming that powerful induced anion–π interactions account for the high catalytic activity. Twenty

• equivalents of the π-acidic intercalator 38 increased the catalytic activity of fullerene dimer 37 by 20%. This increase was consistent with the formation of the π-stacked complex 39 with increased polarizability and electron deficiency. With the π-basic intercalator 40, the catalytic activity of fullerene

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

• homogeneous reaction. For example, by incorporating a lipophilic side chain [28] on the organocatalyst that does not interfere with its catalytic activity thanks to a linker between the catalyst and lipophilic units. In this way, a significant difference in polarity can be achieved between the catalyst and

• cinchona squaramide organocatalyst. Its catalytic activity and recyclability were examined in a new stereoselective synthesis of baclofen, which is used to treat muscle spasms [30]. Finally, the catalyst was easily recycled by centrifugation over five reaction cycles without significant loss of activity

• applied between the catalytic and lipophilic units to avoid a decrease in the catalytic activity. The demethylated cinchona squaramide 6 was reacted with O-p-toluenesulfonyl-N-Boc-ethanolamine. The protecting group was removed using trifluoroacetic acid, followed by a neutralization step, gaining the

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• detect, if the two polymorphs show different catalytic activity, as in the following investigations the amorphic powder was used. Spectroscopic and electrochemical characterization The Co(II) complex 1 was characterized by UV–vis absorption spectroscopy in N,N-dimethylacetamide (DMA), as it was the

• . Thus, aiming at enhancing the catalytic activity, we performed some additional photocatalytic tests, upon the addition of different concentrations of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP). This alcohol has interesting physical and chemical properties, and, being well miscible with many organic

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• yield by reacting [Cu(CH3CN)4]BF4 with 2 equiv of benzimidazolium salt 38 in the presence of NaOt-Bu (Scheme 14) [28]. The catalytic activity of the complex 39 was studied in the [3 + 2] cycloaddition of azides with alkynes [28]. Coyle et al. reported the synthesis of a series of NHC and ADC (acyclic

• [(IMes)2Cu]+FHF− (91) was also obtained. These complexes exhibit an interesting catalytic activity that will be described later. 2 Application as catalysts In 2001, Woodward, for the first time, reported an NHC–Cu-mediated catalysis in the conjugate addition of diethylzinc to enones (Scheme 33) [46

• been found to be highly efficient catalysts in this transformation. Nolan and co-workers reported the catalytic activity of [Cu(IPr)Cl] in the hydrosilylation of carbonyl compounds to form silyl ethers in high yield [48][49]. A series of bis-NHC–copper complexes was synthesized and the compounds were

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

• pyrroles/indoles 4/9 allowing access to 2,3-dihydroisoxazoles 77/78 bearing an all-substituted stereocenter at the C3 position. A dual catalytic activity of the Brønsted acid catalyst was illustrated by the authors which was initiated with a smooth protonation of the OH group in 76 with a subsequnte

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• magnetically recoverable by simple magnetic decantation. In addition, the catalytic activity of the catalyst remains unaltered after six consecutive cycles (Figure 3). Using this catalyst, various nitrogen-substituted pyrrole derivatives 31 were synthesized in 55–96% yields through the reaction between various

• effect on product yield and no loss of catalytic activity. Moreover, a plausible mechanism for the constructions of N-arylpyrroles is shown in Scheme 17b. In the first step, the acetal group of 2,5-DMTHF (2) is protonated by β-CD-SO3H to produce intermediate A. Intermediate A is nucleophilically attacked

• of the catalyst for up to nine consecutive runs without loss of catalytic activity. Recently, Rohit et al. [86] described a modified Clauson–Kaas synthesis of N-substituted pyrrole with up to 89% yields by microwave irradiation at 120 °C in neat conditions by reacting amines 66 with 2,5-DMTHF (2) in

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• 1,4-dioxane the transformations performed the best (Table 1, entries 3–5). A series of copper catalysts such as CuI, CuCN, and Cu2O was screened, in which some showed good catalytic activity (Table 1, entries 6–9), and Cu2O was identified as the most effective catalyst for the desired transformation

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• also found to have a higher catalytic activity for the ortho-alkylation of pyridines with styrenes to give the linear alkylated products (5b,c, Scheme 2). Further, the authors proposed that the C–H bond activation could be the rate limiting step based on kinetic isotope experiments (KIE). The proposed

• which resulted in C3-alkylated pyridines 51. Based on the reactions performed for the catalytic activity of the silyl-iridium complex, the authors proposed a catalytic mechanism (Scheme 11b). The mechanism involves the initial formation of the active silyl-iridium catalyst A which through oxidative

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

• ) with its counterpart from the liquid state transmetallation route (5ls) in catalysis. We found that 5bm was catalytically active, however displaying slightly diminished activity in general most likely due to different adduct ratio inhibiting the catalytic activity (Scheme 3). This was established using