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

• stereoselectivity of KR is controlled solely by KRC, and KRS does not influence its catalytic selectivity. Moreover, A2- and B2-type KRCs formed a separatable clade from A1- and B1-type KRC, respectively, suggesting that phylogenetic analysis can be used for stereochemical prediction. It is noteworthy that A0- (0

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• distinct advantageous such as (i) the methodology does not require the presence of any metal moities, (ii) enables the synthesis of corresponding oxyfluorinated analogues with high yields and selectivity, (iii) allows derivatization of natural chiral molecules, (iv) uses a safe solvent in mild reaction

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

• possibly due to greater dispersive and lesser repulsive forces for larger halogens. This finding may prove useful in catalyst design where close spatial proximity of the substrate to other important structural information (i.e., chirality) has an impact on selectivity. Our analysis of selected XB complexes

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

• furnishing the corresponding alcohol (D) and acid molecule (E). Review Modernization of the Cannizzaro reaction Researchers have always aimed to improve the efficiency, selectivity, and sustainability of reaction processes. The development of reagents, solvents, and application of modern technology frame the

• 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

• % enantioselectivity. They employed a double asymmetric induction with (+)/(−)-menthol (12), and CuX2 bis(oxazoline) catalyst where the corresponding chiral mandelate ester 13 was obtained in 81% yield and high selectivity (90% de) (Scheme 6). The proposed mechanism of the reaction is depicted below. Hong et al

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

• and acyl radicals and maintaining a high degree of selectivity with respect to the desired outcome are key obstacles to the growth of alkyl and acyl radical chemistry. With this in mind, the emergence of new chemical transformations involving radicals generated via C–O bond cleavage by visible light

• light, a sustainable and abundant energy source, to initiate chemical reactions. This approach offers milder reaction conditions, which often result in improved selectivity and functional group compatibility. Additionally, it allows the activation of typically inert bonds and can enable the development

• of novel synthetic strategies. It has expanded the scope of available synthetic methods and contributed to the synthesis of complex molecules with high efficiency and selectivity. Ongoing research in this field continues to explore new catalysts, photosensitizers, and reaction mechanisms to further

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• a hydride donor [5][6][7][8]. On the other hand, aryl radical-involved hydroarylation would be a promising alternative for the synthesis of alkylarenes with high anti-Markovnikov selectivity [9][10]. Aryl halides have received increased attention as ideal radical precursors because of their

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• diameter range. The diameter selectivity is supported by the theoretical calculations with the GFN2-xTB method, indicating that the most preferred SWNT diameter for the square Cu-nanobrackets is 1.04 nm. Keywords: complexation; diameter; extraction; interlock; nanobracket; single-walled carbon nanotubes

• square in its shape by changing anthracene in 1a to pyrene in 1b. To interpret the results of the diameter selectivity, the theoretical calculation using the semiempirical tight binding quantum chemical method GFN2-xTB was employed instead of the molecular mechanics used in our previous works, because it

• summarized in a graphene map (Figure 5c). This shows that Cu-nanobrackets 1b preferentially recognize larger diameters with wider range (0.94–1.10 nm) than 1a (0.90–0.92 nm) due to the larger cavity with more flexibility of 1b than 1a. Theoretical calculations To interpret the diameter selectivity, the

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• the chromone moiety was observed for 3-(2-nitrobenzoyl)chromone, presumably due to steric hindrance. The same selectivity was observed also for 3-trifluorochromone and 3-perfluoroalkanoylchromones which might be explained by the fact that the carbonyl adjacent to the perfluoroalkyl group exists as a

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

• compounds. To achieve the selective C–C and C–N bond formation via hydrogen borrowing, controlling the selectivity is an important factor since the formation of possible side-products such as overreduction of unsaturated compounds or dialkylation. Hence, developing an efficient catalyst, capable of

• indicates that the cation-coordinative interaction with the catalyst plays a significant role. Moreover, the mechanistic investigation suggested that the observed selectivity is due to the more reactive potassium manganate hydride towards the hydrogenation of imines to amines than the sodium manganate

• Mn-pincer (PNP) complex Mn1 at various concentrations. An extraordinary TON (9233) could be achieved at low catalyst loading using 3.5 equiv NaOMe at 200 °C for 48 h with 91% selectivity and 29% yield (Scheme 45) [73]. In 2020, Kempe's group reported an elegant example for the β-methylation of

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• suffer from the generation of stoichiometric amounts of byproducts and often encounter selectivity troubles. To mitigate these issues, we extended the greener peroxide-bromide halogenation method, initially developed for monobromides, to afford aryl-cored polybromides in high yields. The same method can

• ] resulting in easier recyclability. Light irradiation often significantly influences the selectivity of halogenation processes. Photolytic cleavage of molecular halogens gives rise to radicals that are known to favour benzylic functionalisation [17]. Conversely, the same molecular halogens exhibit prominent

• CCl4 to prevent undesired solvent degradation. Furthermore, the direct use of Br2, even if used in low concentration, exhibits limited selectivity towards benzylic bromination, primarily due to co-bromination occurring on the aromatic ring. This side process produces awkward halogenated byproducts that

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

• ] nucleophiles due to their excellent reactivity and aryl group selectivity over aryl(anisyl)iodonium(III) salts [32] and aryl(mesityl)iodonium(III) salts [33]. Based on our previously reported conditions for the synthesis of diaryliodonium(III) salts [21], we designed a more practical synthetic protocol for the

• (TMP)iodonium(III) trifluoroacetate (4m) was obtained in 91% yield. These aryl(TMP)iodonium(III) acetates were recently utilized by our group for the arylation of phenols [13] and N-alkoxyamides [26][29], exhibiting excellent reactivity and aryl group selectivity. In subsequent experiments, we sought

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

• selectivity with the noncanonical prenyl substrates. To enable the biotechnological synthesis of irregular terpenes, the product selectivity of 2-methylenebornane synthase from Pseudomonas fluorescenes was altered using a semi-rational engineering approach [56]. In contrast to GPP methylation, modification of

• products, 3-ethyl-3-buten-1-ol (139) and 3-propyl-3-buten-1-ol (140), have potent fuel properties, highlighting the potential of this strategy for producing isoprenol analogs as next-generation biofuels (Figure 10b) [62]. Conclusion During terpenoid biosynthesis, most TSs have strict substrate selectivity

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• was formed (internal standard: PhCF3, Table 1, entry 1). Pleasingly, changing the base to K2CO3 led to the formation of 2a in 7% 19F NMR yield (Table 1, entry 2), while the selectivity of the reaction could be switched significantly upon employing organic amine bases (Table 1, entries 3 and 4). Using

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

• product 3 show similar reactivity under the employed reaction conditions. Therefore, the reaction had to be optimized to overcome this competition and to achieve a higher yield and selectivity for the desired product (Supporting Information File 1, Table S1). Finally, the transformation was realized by

• using Pd(PPh3)Cl2 (5 mol %), CuI (5 mol %), NEt3 (10 equiv), DMSO, at 25 °C for 6 h as reaction conditions with excellent yield and selectivity. With the optimized conditions in hand, the next step was to investigate the scope and afford 3a–j. The corresponding results are depicted in Scheme 2. The

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

• reaction of azoles with alkynes and iodine(III) electrophile, benziodoxole triflate (BXT, 1; Scheme 1c). Displaying exclusive trans-selectivity, the reaction tolerates a broad range of azoles, including pyrazole, 1,2,3-triazole, tetrazole, indazole, and benzotriazole, with internal alkynes as coupling

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• . Keywords: annulation; arylocyclization; 3,4-benzocoumarin; diaryliodonium salts; naphthol; Introduction Diaryliodonium salts as electrophilic reagents have attracted significant attention in the field of organic synthesis owing to their efficiency and selectivity [1][2][3][4][5][6][7]. Particularly, they

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• mixture of ketone 9e and the O-alkylated enol ether by-product, which was then reduced using NaBH4 to give alcohol 10e with 98:2 selectivity. Similarly, the reaction of 4-methoxybenzyl bromide and 2 gave ketone 9f in 35% yield without chromatography, and when reduced resulted in only a single alcohol

• stereoisomer 10f in 91% yield. The selectivity of the NaBH4 reduction was confirmed for both 10d (see discussion in Supporting Information File 1) and 10e by X-ray crystallography (Figure 2 and Scheme 1, respectively). The oxygen-migration reaction giving 11a was initially observed using the readily available

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• to note that CavA exhibits limited substrate promiscuity, predominantly targeting the drimenol skeleton with minor variations. This selectivity may be attributed to the structural configuration of the enzyme, which appears to be finely tuned to recognize and interact with specific features of the

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• 19 with HCl/Et2O [44]. This selectivity is notable, especially when compared to reports by other groups indicating the formation of the corresponding phenol derivative under prolonged reaction times (see Scheme 9). Honda reported a quantitative yield in the hydrochlorination of 21 with an ethereal

• octahydronaphthalene (31) and hexahydroindene 33 (Table 2 and Table 3). However, in the case of compound 31, the cis-selectivity was relatively low (Table 2, entry 1). Recently, Frøyen and Skramstad studied the hydrochlorination of 1,2-disubstituted alkenes with HCl gas (Scheme 6) [50]. Numerous unsuccessful attempts

• affording chloride 51 as a mixture of cis- and trans-isomers. The hydrochlorination of 1,2-dimethylcyclohexene (29) resulted in high selectivity for trans-30. The authors also showed that an increase in ethanol to 40 equivalents led to a dramatic drop in yield, likely due to an overall lower concentration

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• [8]. Further improvement of the PDT method requires the search for new photosensitizers having higher photoactivity, tumor selectivity, and high singlet oxygen quantum yield, as well as low in vivo toxicity [7]. Therefore, some strategies have been developed to enhance the therapeutic efficiency of

• known to enhance the aqueous solubility and tumor selectivity of hydrophobic drugs through the enhanced permeability and retention effect [46]. It was also shown that porphyrin 6 undergoes reaction with taurine (2-aminoethanesulfonic acid, 25) which is an essential nutraceutical with diverse

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• cyclization and hydrolytic activities that are not easily predictable, related mechanism studies indicated that the pre-reaction states of the enzyme and substrate are critical for selectivity [15][16]. Thus, both the mutation of key residues in the active pocket and the addition of a nonionic detergent can

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• hours without compromising selectivity. Although tetrabutylammonium azide (TBAA) is better soluble in DMSO than NaN3, practical challenges associated with its use led to the preference for NaN3. Confirmation of regioselectivity for the sulfonyl group dance products The regioselectivity and the structure

• MeCN and THF gave only product 17a, but in DMSO resulted in the mixture of 17a/18/6,7-dimethoxy-2,4-di(pyrrolidin-1-yl)quinazoline = 36:15:48% (HPLC analysis). The selectivity of 17a/18 was interesting but was not further developed in the scope of this study. Consequently, an investigation into the

• selectivity was reached only in polar solvents such as DMF, DMSO, and MeCN. In other solvents, no reactivity was observed at the C2 or C4 positions. Selective modification of the C2 position of 6,7-dimethoxyquinazoline Products 12 are useful intermediates to achieve selective modification at the C2 position

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• temperature (rt), the desired unsaturated ε-AA derivative 4a was obtained in 75% isolated yield (Table 1, entry 1). Isolation and NMR analysis demonstrated that this model reaction provided amino acid 4a with good E-selectivity and excellent regioselectivity (E/Z = 91:9, 1,4-/1,2-addition >20:1). Control

• case of 1,3-cyclohexadiene 2e, the amine was expected to attack the π-allyl palladium from the exo side. Considering that substituent effects might affect the regioselectivity in this MCR, we further investigated the 1,4-/1,2-addition selectivity with 1-phenyl-substituted 1,3-dienes 2f–i. Interestingly

• , the corresponding 1,2-addition products 4p–t were formed with high selectivity (E/Z > 20:1, 1,2-/1,4-addition >20:1), presumably due to steric hindrance by the phenyl group. Furthermore, the 1,3-diene bearing a 1-furan group with smaller steric hindrance afforded product 4u with moderate

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• contrast, heteropolyacids (HPAs) have been reported as greener catalysts not only for being a safer alternative to toxic catalysts [41] but also for providing easy recovery and reuse linked to high selectivity [42]. An example of HPA is phosphotungstic acid, H3PW12O40 (HPW), an inexpensive, non-toxic, and

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• . In a recent study, a structural model of AdrI was constructed by AlphaFold2 [14], and its product 9 was docked into the model [15]. In the complex structure, H76 and K187 are located close to the D ring of 9, and are expected to determine the selectivity of the product. The AdrI H76F/K187A variant