pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• ] and experimentally validated their approach using six pharmaceutical intermediates from medicinal chemistry programs. In the article, they state that ”Iridium catalysts ligated by bipyridine ligands catalyze the borylation of the aryl C–H bonds that are most acidic and least sterically hindered…”[45

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

• , non-photochemical, silver-catalysed HAT radical-polar crossover mechanism for nucleophilic benzylic fluorination (Figure 34) [85]. The authors proposed a similar mechanistic pathway to the photochemical methods, citing the use of amide ligands as important for modulating the silver catalyst stability

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

• available CeCl3 (10 mol %) and Cu(OTf)2 (5.0 mol %) together with bidentate nitrogen ligands such as BPhen, Phen, dtbbpy, and bpy with TMSCN as the cyanating reagent promoted the direct conversion of flurbiprofen (1) to the desired product (2) in good yields (Table 1, entries 1 and 2). Cu ions are well

• -known to be highly susceptible to electroplating on the cathode and thus require the use of ligands to avoid detrimental cathode deposition during electrolysis (Table 1, entry 3). In addition, we discovered that the additional use of DMF as co-solvent is beneficial to the reaction efficiency–reactions

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• antibiotic-sparing anti-infective drugs. Building synthetic glycoconjugates for the inhibition and modulation of bacterial lectins have shown promising results. Light-sensitive lectin ligands could allow the modulation of lectins activity with precise spatiotemporal control. Despite the potential of

• photoswitchable tools, few photochromic lectin ligands have been developed. We have designed and synthesized several O- and S-galactosyl azobenzenes as photoswitchable ligands of LecA and evaluated their binding affinity with isothermal titration calorimetry. We show that the synthesized monovalent glycoligands

• due to stronger unfavorable entropy, they are in general of lower affinity. The validation of this proof-of-concept and the dissection of thermodynamics of binding will help for the further development of lectin ligands that can be controlled by light. Keywords: carbohydrates; glycosyl azobenzenes

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

• consistent with Bent’s rule in which greater p-character is directed toward more electronegative ligands [44]. We also consider a correlation between Vs,max of the halogen-bond donor and ΔG of the halogen bond (Scheme 6c) [45]. Although a modest linear correlation (R2 = 0.90) was observed over all data

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

• related to Ewing sarcoma [8], IGF-1 receptor inhibitors [9] or act as ligands on corticotropin releasing hormone (CRH) [10], γ-aminobutyric acid (GABA) [11] and melanocortin receptors [12]. Given the established potencies of this class of N-ring-fused compounds, planned syntheses that simplify their

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

• will then enable soft nucleophiles such as unadorned amides to readily participate in the ensuing olefin addition. In this regard, we wondered if the hypervalent iodine with difluoro ligands could undergo salt metathesis with lithium salts such as LiBF4 or LiPF6 to afford the more reactive cationic

• iodine catalyst with difluoro ligands. Interestingly, the use of different lithium salts also impacted the overall reaction rate, with the reaction using the less coordinating LiAsF6 salt proceeding faster than LiPF6 and LiBF4. This time study suggested that the hypervalent iodine precatalyst with the

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

• represented in the table below. The yields and selectivity were found to be superior compared to bisoxazoline (BOX) ligands, which was attributed to the steric bulk imparted by the ligand at the stereoinduction step. Increasing the steric size of the alcohol also contributed to the increased

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

• conventional metal hydrides, such as tin or silicon hydrides. The reaction mechanism is interesting since first, a Lewis acid–base adduct is generated by interaction of Et3N with a boron atom of bis(catecholato)diboron (B2cat2, 19). As a result, one of the catecholate ligands experiences an increase in

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

• ][23], dyes, preservatives and as ligands in complex chemistry [24][25][26][27]. In the context of our interest in the application of cross-coupling reactions to polyhalogenated heterocycles [28][29][30][31], we studied Sonogashira reactions of brominated 2-trifluoromethylquinolines. The optical

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• . The regioselectivity in the addition reaction of 1 with C70 was explained earlier in terms of the interaction between the HOMO of 1 and the LUMO of C70 [16]. The reaction mechanism of ethylene with a silylene substituted with thiolate ligands has been studied using theoretical calculations, in which

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

• alcohols [39]. Various ligands were screened for the N-alkylation of m-toluidine with benzyl alcohol using Mn(CO)5Br (5 mol %) and t-BuOK (1 equiv) in toluene at 140 °C (Scheme 9). Among these, L1 and L2 showed better activity for the N-alkylation reactions. Different substituted anilines and alcohols

• bearing bidentate amine-based ligands and studied them in the N-alkylation of aromatic amines with benzylic alcohols (Scheme 17). Under the optimized reaction conditions (140 °C, 24 h), complex Mn8 (2 mol %) was successfully applied for the coupling of various electron-donating and withdrawing primary

• for the direct β-alkylation of secondary alcohols with primary alcohols [71]. The reaction conditions were investigated for the alkylation of 1-phenylethanol with benzyl alcohol using manganese complexes containing pyridyl-supported pyrazolyl-imidazolyl ligands and bases. Among these complexes, Mn17

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• of HeE1-2Tyr (1), it must be considered that the synthesized ligands were significantly smaller in size. Normalization of the obtained results using the binding efficiency index (BEI) [32] suggest that both ligand types, 3a–c and 4a,b, bind more efficiently to the SARS-CoV-2 RdRp when compared to 1

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• design diaryliodonium(III) salts including a commercially available and inexpensive auxiliary group to achieve efficient preparation of the salts and a high degree of chemoselectivity for transferring the required aryl group. Electron-rich aryl ligands derived from anisole, mesitylene, and particularly

• various new applications. Synthetic approaches of diaryliodonium(III) trifluoroacetates. Synthesis of diaryliodonium(III) carboxylates. Scope of dummy ligands. Substrate scope of aryl(TMP)iodonium(III) acetates. a) 0.50 mmol scale of 1i. b) 1,3,5-Trimethoxybenzene (2.1 equiv) was used. c) Bis

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

• as ligand, because it was already known that catalysts derived from palladium(II) salts and bidentate nitrogen ligands were highly reactive systems for the reduction of o-nitrostyrenes [28][29][30]. The catalytic system Pd(OAc)2/1,10-phen worked better than Söderberg´s one (Pd(OAc)2/PPh3) under mild

• -2,3-diyl)bis(3-nitropyridine) was performed. All reactions were carried out in the presence of Pd(dba)2 as catalyst, dppp and 1,10-phen as ligands under 6 bar of CO at 120 °C for the appropriate time. The processes to 2,2′-bi-1H-indoles, 2,3′-bi-1H-indoles, and 3,3′-bi-1H-indoles were selective

• of the Pd(dba)2/dppp/1,10-phen catalyst system. Synthesis of indoles from o-nitrostyrenes by using Pd(OAc)2 and Pd(tfa)2 in conjunction with bidentate nitrogen ligands: 1,10-phen (1,10-phenanthroline) and tm-phen (3,4,7,8-tetramethyl-1,10-phenanthroline). Synthesis of substituted 3-alkoxyindoles via

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• . Classically, these prenyl analogs have been used as co-crystallization ligands [38], inhibitors of specific TSs [39], and tools to study the reaction mechanisms of cyclization cascades [40][41] which have been comprehensively addressed in important previous reviews [8][13]. Currently, noncanonical prenyl

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• commercial drug baclofen as hydrochloride. Keywords: desymmetrization; enantioselective Heck–Matsuda reaction; lactam synthesis; N,N-ligands; palladium; Introduction Desymmetrization reactions consist in the modification of a molecule with the loss of one or more symmetry elements, such as those which

• preclude chirality as in the transformation of a prochiral molecular entity into a chiral one [1]. It is a powerful and elegant strategy in asymmetric synthesis [2], which combined with the use of chiral ligands and transition-metal catalysts enabled many valuable transformations to increase molecular

• before. Before exploring the reactivity of the olefin towards other aryldiazonium salts, we performed a brief optimization of the process by testing several other N,N-ligands. Therefore, five other N,N-ligands were evaluated as follows: PyraBox (L2), QuinOx (L3), PyOx L4 and L5, and PyriBOx (L6) (Figure

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• effort was then focused on the optimization of the intramolecular Heck reaction of 5a for making 1,2,3,4-tetrahydroisoquinoline 6a. A systematic evaluation of different catalysts and ligands, solvents, bases, as well as reaction temperatures and times was conducted (Table 1). The Heck reaction of 5a was

• both gave cyclized product 6a in 70% yield (Table 1, entries 3 and 4). An increase of the reaction time to 12 h did not improve the yield (Table 1, entry 5). The reaction was further evaluated in the absence of ligand which afforded the product in 35% yield (Table 1, entry 6). Screening of ligands, e.g

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

• performed on a Bruker Apex Kappa-II CCD diffractometer. The solvents used, dimethyl sulfoxide and 1,4-dioxane, were purchased as dry solvents and applied without further purification. Other reagents, catalysts, ligands, acids, and bases were used as purchased from commercial suppliers. Column chromatography

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

• Jan Bartacek Karel Chlumsky Jan Mrkvicka Lucie Palousova Milos Sedlak Pavel Drabina Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic 10.3762/bjoc.20.62 Abstract The new chiral ligands I–III

• depends on the relative configuration of the ligand used; cis-configuration of ligand affords the nitroaldols with major enantiomer S- (up to 97% ee), whereas the application of ligands with trans-configuration led to nitroaldols with major R-enantiomer (up to 96% ee). The “proline-type” ligand IV was

• also tested in asymmetric aldol reactions. Under the optimised reaction conditions, aldol products with enantioselectivities of up to 91% ee were obtained. Keywords: asymmetric aldol reaction; asymmetric Henry reaction; chiral ligands; enantioselective catalysis; imidazolidine derivatives

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• introduced by the groups of Lassaletta [4] and Glorius [5], is the most widely explored framework for L-shaped ligands (Figure 1a). Even when only considering gold catalysis [6], the ImPy framework has been used to great effect [7]. The motif has been used to introduce sterically demanding NHCs with

• secondary gold-ligand interactions [8][9][10], chiral environments [11][12][13] including those enabling secondary interactions with substrates for asymmetric catalysis [14], cooperative and bimetallic catalysis [7][15], and redox-enabling function for Au(I)/(III) cycles [16][17]. Such L-shaped ligands

• only two sharp CO stretching frequencies were observed in the IR (Scheme 2) and so a value for Tolman’s electronic parameter (TEP) could be estimated. [33] At TEP[Ir] = 2053.1 cm−1 and 2052.8 cm−1 for 15a and 15b, respectively, the values for these AImOx ligands are towards the electron-deficient end

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• with emphasis on the structural diversity of small-molecule ligands. In this context, acyl-acyl carrier protein (acyl-ACP) thioesterase inhibitors have shown a remarkable variability. Fatty acid thioesterase (FAT) enzymes represent a family of proteins exclusively found in higher plants. They mediate

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

• can abduct it from the terpyridine. The luminescence properties in the closed state can also be modulated by the formation of host–guest complexes. This happens with ligands complexing the metal center only, such as terpyridines and phenanthrolines. In fact, the counterions of the zinc2+ cation and

• bisalkynylplatinum(II)–terpyridine clips [54]. The dimer showed photocatalytic activity in the photooxidation of a secondary amine to the corresponding imine that could be deactivated and reactivated by opening or closing the tweezers. Variations on multidentate N-donor ligands have also been developed by Lehn and

• regulated guest binding. Other groups developed coordination-switchable molecular tweezers with several ligands based on nitrogen coordination sites. Plante and Glass reported tweezers 23 using a bisimidazole-pyridine unit with anisole arms (Figure 14a) [55]. This system can coordinate copper(II) in a

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

• out under a variety of conditions with cationic gold catalysts supported by phosphine ligands. The impact of ligand on gold, protecting group on nitrogen, and solvent and additive on reaction rates was determined. The most effective reactions utilized more Lewis basic ureas, and more electron

• require geminal substitution or backbone heteroatoms, internal alkenes are often not tolerated, and intermolecular reactions require high temperatures which can lead to significant catalyst decomposition [20]. This is usually addressed by employing bulky or strong donor ligands [21][22]. Novel strategies

• 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

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• ligands was examined. Slightly better yields of 1 were obtained using the diphosphine ligands dppe, dppb or dppf associated with Pd(OAc)2, and the preformed catalyst PdCl(C3H5)(dppb) gave 1 in 74% yield (Table 1, entries 7–10) [26]. The influence of a variety of solvents was also examined. DMF and NMP