Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• , PDB ID: 6UAK (https://doi.org/10.2210/pdb6UAK/pdb), [72]. The residues involved in SAH binding are depicted in red. Reaction scheme of the PAMT´s catalysis, leading to the enzymatic conversion of aspartate to aspartyl-O-methyl ester, followed by a two-step non-enzymatic conversion via succinimide

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• . This review aims to give context to these transformations and strategies, highlighting the different tactics to achieve fluorination of benzylic C–H bonds. Keywords: benzylic; C–H functionalization; fluorination; photoredox catalysis; Introduction The development of new fluorination methodologies is

• monofluorination radiolabelling using [18F]NFSI. Electrophilic fluorination of benzylic C–H bonds has been demonstrated as a powerful approach. However, these techniques can be constrained to defined substrate classes and the requirement of using strong bases. Palladium catalysis Palladium-catalysed chemistry is

• solubility issues of metal fluoride salts, safety issues with hydrogen fluoride, poor nucleophilicity [79], and side reactivity as a base [75][79], a few elegant examples of nucleophilic benzylic C(sp3)–H fluorination have been reported. Metal catalysis Fluoride sources have been used in combination with

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• yields (up to 97%) and high enantioselectivities (up to 98.5% ee) under mild reaction conditions. In addition, this protocol was further expanded to synthesize highly enantioenriched hybrid molecules bearing biologically relevant heterocycles. Keywords: α,β-unsaturated ketones; iminium catalysis

• -covalent catalysis via bifunctional hydrogen-bonding organocatalysts. The C-4 nucleophilicity of pyrazolin-5-ones was also explored in enantioselective reactions with α,β-unsaturated carbonyl compounds through covalent catalysis with chiral amine-based catalysts; however, it has achieved limited success

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• catalysis concept for such transformations [32][33][34][35][36]. These oxidative approaches, which usually proceed via the in situ formation of catalytically-competent ammonium hypoiodite species, can normally be carried out under operationally simple conditions, thus allowing for the use of easily

• remarkable advancement in this field (Scheme 1B [31]). In contrast to previous oxidative quaternary ammonium iodide catalysis reports [28][29][30], this method does not require the use of TMSN3, thus presenting an efficient oxidative α-azidation protocol utilizing NaN3, which arguably represents the most

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• ; quaternary ammonium salt catalysis; Introduction The development of asymmetric synthesis routes to access non-natural amino acids has for decades been one of the most heavily investigated tasks in organic synthesis and catalysis-oriented research [1][2][3][4][5][6][7][8][9][10][11][12][13]. As a consequence

• variety of asymmetric α-carbo- and α-heterofunctionalization reactions by utilizing different catalysis strategies [20][21][22]. We have recently carried out systematic investigations concerning the syntheses of advanced β-AA by means of asymmetric α-carbofunctionalization reactions and during these

• studies we also realized that the masked β-AA derivatives 2 undergo enantioselective β-addition to allenoates 3 under chiral ammonium salt catalysis (Scheme 1B) [18]. Interestingly, hereby we also found that the use of alternative catalyst systems (i.e., tertiary phosphines) allows for a γ-selective

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• different types of aliphatic acids including primary ones could be successfully employed (Figure 1B, reaction 1). The groups of Waser [23] and Gonzalez-Gomez [24] reported the direct conversion of aliphatic acids to the corresponding alkylnitriles by merging photoredox catalysis and radical cyanation

• electrophotochemical transition metal catalysis [26][27][28][29][30][31] as a unique and powerful synthetic platform for radical decarboxylative functionalization of aliphatic carboxylic acids [32][33][34][35][36][37]. In particular, the commonly required high activation energy for radical decarboxylation was provided

• invention of cooperative catalysis with electrochemical transition metal catalysis, which generally has mild oxidation potential for the generation of persistent radicals in the form of nucleophile-bound metal complexes. We and other groups have successfully applied this reaction design to enantioselective

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• of DH-ER-KR tridomain (Figure 2c). This finding suggests that the helix αB may have an allosteric interaction with DH or potential large conformational changes between DH and KR during catalysis. Sequence logo analysis of KRC from β-modules Based on the clear stereoselectivity-dependent clades

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model

• Yingbo Shao,
• Zhiyuan Ren,
• Zhihui Han,
• Li Chen,
• Yao Li and
• Xiao-Song Xue

Beilstein J. Org. Chem. 2024, 20, 1444–1452, doi:10.3762/bjoc.20.127

• ; machine learning; Introduction Hypervalent iodine reagents are increasingly gaining attention in the fields of organic synthesis and catalysis due to their environmental benefits, accessibility, and cost-efficiency [1][2][3][4][5][6][7][8][9][10][11]. Over the last three decades, a series of cyclic

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• diarylhalonium salts in halogen-bonding catalysis [13][14][15][16][17][18][19]. Crabtree has outlined the similarity in molecular orbitals (MO) formed in halogen bonds and hypervalent bonds (and hydrogen bonds) [20]. Recently, we [21], and Legault and Huber [22], independently investigated the connection between

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• remarkable advantages such as an environmentally benign alternative to traditional transition-metal catalysis, a low cost, nontoxicity, good stability, and easy handling [30][31]. Upon increasing the amount of FeCl3 to 20 mol %, the time of the reaction was reduced from 86 to 38 hours, and the yield of 5a

• represents an interesting example of auto-tandem catalysis in which FeCl3 promotes two subsequent reactions. For further confirmation to support our mechanistic hypothesis and in an attempt to switch the reaction toward the formation of hemiaminal 6a, we repeated the reaction of thiohydantoin 4j, (chosen as

• corroborate our mechanistic hypothesis related to the formation of both N,O-aminals and corresponding hemiaminals. In particular, the domino reaction that leads to the carbinolamines represents an interesting example of “auto-tandem catalysis” in which the FeCl3 catalyzes two different chemical

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• .20.122 Abstract Hypervalent iodine catalysis has been widely utilized in olefin functionalization reactions. Intermolecularly, the regioselective addition of two distinct nucleophiles across the olefin is a challenging process in hypervalent iodine catalysis. We introduce here a unique strategy using

• simple lithium salts for hypervalent iodine catalyst activation. The activated hypervalent iodine catalyst allows the intermolecular coupling of soft nucleophiles such as amides onto electronically activated olefins with high regioselectivity. Keywords: amide coupling; hypervalent iodine catalysis

• catalysis, which often involves the catalytic use of an iodoarene with stoichiometric oxidants such as MCPBA, Selectfluor, etc. [18][19][20]. Earlier and recent hypervalent iodine-catalyzed olefin halofunctionalizations by several groups have predicated on the use of intramolecular olefin substrates

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• numerous modified techniques, which established the greener side of the reaction. The use of Lewis acid catalysis in this regard [34][35][36][37][38][39] played a significant role, which also suppressed the epimerization in the case of chiral molecules. Among the various Lewis acid catalysts such as

• methodologies, such as Lewis acid catalysis, desymmetrization of symmetrical dialdehydes, synthesis of natural products, and building blocks. These modifications constitute the main highlight of this review. The use of modern technology and newer strategies aiming towards industrial benefit is the goal for the

• . developed an asymmetric iron catalyst with the aim of expanding the platform of metal catalysis. Catalysts 14 and 15 proved to be effective in the transformation of glyoxal monohydrates 1a and alcohol 2, to deliver mandelate esters 3a in good yields and enantioselectivities via an enantioselective

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• radicals by activation of C–O bonds using visible-light photoredox catalysis offers a mild and environmentally benign approach to useful chemical transformations. Alcohols, carboxylic acids, anhydrides, xanthates, oxalates, N-phthalimides, and thiocarbonates are some examples of alkyl and acyl precursors

• photocatalysts, transition-metal photoredox catalysts, and metallaphotocatalysts to produce acyl and alkyl radicals driven by visible light. Keywords: acyl radical; alkyl radical; sustainable catalysis; visible light; Introduction The growing awareness of the necessity for sustainable developments has been

• synthesis [4][5][6][7][8][9]. In the context of sustainable catalysis, visible-light-mediated chemistry is becoming a prominent viable option for radical transformations in the synthesis of biologically useful compounds due to the energy efficiency and environmental friendliness [10][11]. Recently, the

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

• catalyst candidates can be found in Supporting Information File 1. In the main article we will focus on catalysis results. We therefore first tested various telluracycle candidates, in particular without an NH bridge (catalyst candidates PTeZ3, Te4–Te7, Scheme 2A). These telluracycles, bridged by very

• . Our future research efforts in the area of Te(II) catalysis will likely focus on milder coupling reactions on the one hand, and/or on novel more robust and more active ligand designs on the other. In particular, more investigations will likely be needed regarding the optimization of the possible Te

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• Amol P. Jadhav Claude Y. Legault Department of Chemistry, Centre in Green Chemistry and Catalysis, Université de Sherbrooke, Québec J1K 2R1, Canada 10.3762/bjoc.20.111 Abstract We have developed an operationally simple method for the synthesis of dialkyl α-bromoketones from bromoalkenes by

• Green Chemistry and Catalysis (CGCC), and the Université de Sherbrooke.

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations

• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2024, 20, 1278–1285, doi:10.3762/bjoc.20.110

• use in different fields of chemistry like synthesis [4][5][6][7][8][9], catalysis [10][11][12][13][14] and materials science [15][16][17][18][19][20][21][22][23]. ILs generally consist of an organic cation [24], such as the imidazolium or ammonium ion and an inorganic anion like a halide anion or

• ionic liquid in addition to the possibility to introduce alkyl chains with varying length [30]. TAAILs have already been successfully used for the synthesis of nanoparticles and as solvents in catalysis [31][32]. Recently we have described the synthesis and physical properties of TAAILs which have been

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• steady state absorption and fluorescence spectroscopy which give insights of the influence of the substitution pattern and of the type of substituents on the optical properties. Keywords: alkynes; catalysis; fluorescence; heterocycles; palladium; Introduction Quinoline is a well-known core structure

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• catalyst in the sulfonylation/arylation of styrenes and as a triplet sensitizer in energy transfer catalysis. The singlet lifetime is sufficiently long to exploit the exceptional excited state reduction potential for the activation of 4-cyanopyridine. Photoinduced electron transfer generating the radical

• underlying reaction mechanism. On the other hand, the relatively high triplet formation quantum yield of Aza-H along with its triplet energy on the order of 2.3 eV permit efficient and metal-free reactions via energy transfer catalysis, as shown for the photosensitized isomerization of stilbene and cinnamyl

• chloride. We believe that our findings pave the way for a broader usage of the inherently chiral polyazahelicene photocatalyst class, both in photoredox and energy transfer catalysis. A) Room-temperature absorption (black) and emission (yellow) spectra of Aza-H recorded in MeCN/H2O (9:1), and fluorescence

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• 3-aryl-1-indanones) in good to excellent yield. The reaction did not require additives and was insensitive to both air and moisture. Preliminary biological evaluation of some indanones showed a promising profile against some human cancer line cells. Keywords: bismuth; catalysis; heterocycles

• ][39][40][41][42][43], and other strategies [44][45]. Although methodologies involving catalysis by Lewis acids are very efficient, including asymmetric versions of the Nazarov reaction, the experimental protocols are quite laborious in most cases, requiring low temperature, an inert atmosphere, or the

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

• Milstein [17] in hydrogenation and dehydrogenation reactions with pincer-decorated manganese complexes, significant progress has been made in manganese catalysis [18][19][20]. Notably, well-defined low-valent diamagnetic manganese(I) complexes have been studied in many catalytic transformations, and

• synthesizing amines, the borrowing hydrogen approach is becoming increasingly popular in catalysis since this method provides an excellent example of a green chemistry and atom-efficient reaction [31][32][33]. This section focuses on manganese-catalyzed C–N bond formation reactions via BH or HA using alcohols

• observed under the established reaction conditions. This pioneering work opened the door for manganese catalysis in BH reactions. However, the high base loading (0.75–1 equiv) was required for this system to attain good yields of the N-alkylated products. Later, the same group developed the second

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• time, Wu and co-workers contributed to the introduction of two new syntheses of N-aroylindole derivatives by means of nickel catalysis. In 2021, they reported a nickel-catalyzed carbonylative cyclization of 2-nitroalkynes and aryl iodides with Co2(CO)8 as the CO source. The reaction was performed in

• reaction was run in toluene at 100 °C for 24 h under 20 bar of CO [56] (Scheme 25). The other example, however, accomplished the synthesis through Rh-catalysis from substrates without halogens in their structure. This synthesis was published by Huang et al. who obtained good results by using [(Cp*RhCl2)2

• particular, Xu and co-workers used tertiary amines for achieving the reaction through a Pd/Cu co-catalysis [60]. The 17 examples were obtained by using PdCl2 (10 mol %) as catalyst and Cu(TFA)2∙H2O (30 mol %) as co-catalyst. At the end of the process the catalyst underwent reduction, and therefore, in order

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• of different functional groups was tested. The influence of different functional groups on the physical properties was studied by ultraviolet–visible (UV–vis) and fluorescence spectroscopy, providing new insights into the potential applications of uracil-based structures. Keywords: catalysis; cross

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• catalysis encompassed various azoles such as pyrazole, indazole, and (benzo)triazole, exhibiting high Z-selectivity. In addition, Cao et al. reported a gold-catalyzed addition of 5-substituted tetrazoles to terminal alkynes [11]. Analogous hydroazolation reactions of alkynes have also been achieved under

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• haloalkylation with alkyl iodides (Scheme 14A) [27][47]. This reaction can be performed either under photoredox catalysis conditions or without the need for an initiator, depending on the used alkyl iodide. For selected examples, the radical initiator Et3B could also be used. Activation by photoredox catalysis

• was developed by Anderson and co-workers and was shown to be the more versatile than initiator-free activation. Both initiator-free and Et3B-initiated reactions only tolerated electrophilic radicals (to 134a and 134e), while photoredox catalysis also tolerated electron-rich radicals (to 134b). The

• methylation of the intermediate diacid. As for the 1,2-cubanes, the authors were able to derivatise this general building block into a range of other 1,3-cubanes via metallophotoredox catalysis using acid 167 and redox active esters 168 and 169 (Scheme 17B) [51]. Arylation (to 170), amination (to 171) and

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• Julien Borrel Jerome Waser Laboratory of Catalysis and Organic Synthesis, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL SB ISIC LCSO, BCH 4306, 1015 Lausanne, Switzerland 10.3762/bjoc.20.64 Abstract We report the detailed background for the

• reaction. Radical-polar crossover Due to the disappointing results obtained with EBX reagents as SOMOphilic alkynes, we turned our attention to the development of a radical-polar crossover approach using photoredox catalysis. The final results obtained were described in our previous publication [45], but

• Fédérale de Lausanne for financial support. This publication was created as a part of NCCR Catalysis, a National Center of Competence in Research funded by the Swiss National Science Foundation (Grant No. 180544).