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

• ). The function of squaric acid as a catalyst was not clear, but the authors suggested that the Brønsted acidity of squaric acid affects the reactivity and selectivity of this process. The tentative mechanism of this protocol was proposed (Scheme 13b), in which a reversible acid–base reaction of aniline

• bispyrroles in good yields and high selectivity. To control the selectivity for the synthesis of mono- and bispyrrole-containing compounds, two different reaction conditions have been used. One equivalent of 2,5-DMTHF (2) was used for the synthesis of monopyrroles under reflux conditions for 2 hours, whereas

• °C (Scheme 35). This solvent-free protocol has many advantages, including better selectivity and excellent product yields, mild reaction conditions, and ease of product isolation. (iii) Microwave-assisted reactions under organic solvents: Silveira and co-workers [90] developed the Clauson–Kaas

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

• the construction of a range of δ-olefin-containing aliphatic nitriles with (E)-configuration selectivity. This new method features wide substrate scope, mild conditions, and direct N–O activation. Keywords: direct N–O activation; E-selectivity; nitrile synthesis; ring-opening cross-coupling; sulfuryl

• 1a and facilitate the ultimate addition process. The selectivity of bases for different processes may attract significant attention for further applications. In order to understand the mechanism of the aforementioned transformation, some experimental investigations were performed as described in

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• , because of their particular chemical and physical properties [15]. In addition to ester/amide synthesis, enoyl imidazolides were developed as excellent Michael acceptors. Acylimidazoles are unique electrophiles that demonstrate moderate reactivity, relatively high stability, chemical selectivity, and high

A fluorescent probe for detection of Hg²⁺ ions constructed by tetramethyl cucurbit[6]uril and 1,2-bis(4-pyridyl)ethene

• Xiaoqian Chen,
• Naqin Yang,
• Yue Ma,
• Xinan Yang and
• Peihua Ma

Beilstein J. Org. Chem. 2023, 19, 864–872, doi:10.3762/bjoc.19.63

• aminopropyl-1-pyrenebutanamide (PBA) was also constructed to detect Fe3+ and Ag+ ions in aqueous solution [33], which can be used as a potentially useful fluorescent sensor. Pang and co-workers found that the fluorescent probe of cucurbit[8]uril (Q[8]) and squaraine dye (SQ2) has a high selectivity for Hg2

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 achieving selectivity is difficult due to its ubiquitous nature [40]. The metal-catalyzed C–H bond functionalization is a good strategy for synthesizing highly functionalized organic frameworks. In this context, the C–H alkylation is one of the most important C–C bond-formation reactions [41][42

• containing bioactive molecules (Scheme 10). To attain enantioselectivity a chiral phosphine oxide (43)-ligated Ni–Al bimetallic catalyst was used that was critical in improving the reactivity and controlling the selectivity of the reaction. Further, based on deuterium labelling experiments, KIE studies, and

• iridium catalysis was achieved by Shi [61] in 2010 through an unusual meta-selectivity for the first time (Scheme 11a). To achieve meta-selectivity, the group has screened various transition metals and revealed that a silyl-iridium complex promoted the addition of meta-pyridyl C–H bonds to aldehydes 50

Bromination of endo-7-norbornene derivatives revisited: failure of a computational NMR method in elucidating the configuration of an organic structure

• Demet Demirci Gültekin,
• Arif Daştan,
• Yavuz Taşkesenligil,
• Cavit Kazaz,
• Yunus Zorlu and
• Metin Balci

Beilstein J. Org. Chem. 2023, 19, 764–770, doi:10.3762/bjoc.19.56

• by NMR experiments. Mechanism: For the formation of the compound 6 we proposed the following mechanism: the double bond in norbornene is pyramidalized in the endo direction [11]. Norbornene exclusively undergoes an exo attack upon treatment with bromine. This exo selectivity [12][13] in norbornene

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• regioselectivity. A later correction to the article revised the yield from 99% to 70% and with overall poorer selectivity [59]. The correction is in line with reports of poor selectivity when performing intramolecular Heck reactions (cf. Jepsen et al. [60]). An analogous reaction pathway by Jepsen et al. [60] was

• used to synthesise dibenzo[b,f]thiapines 1c and dibenzo[b,f]oxepines 1b in three steps through a styrene (95 and 96) intermediate (Scheme 19). While the reported conversion was excellent, the yield was low due to moderate selectivity, resulting in a mixture of 7-endo (1c and 1b) and 6-exo (97 and 98

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• . Such a change in the reaction selectivity could be explained by the influence of a higher nucleophilicity of the examined alkylamines in comparison with benzylamine. Then, we tried to involve less nucleophilic amines to the proposed approach. For these, we examined a reaction of APBTT 1a with aniline

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• enolate-trapping tandem sequence using various vinylsilanes 33 (Scheme 8B), allyl halides 35, and benzyl bromide (37) (Scheme 8C) [36]. Although the asymmetric conjugate addition step routinely provided excellent selectivity (93–96% ee), only a moderate to good diastereomeric ratio was achieved

• trapping by adding MeLi (1.05 equiv), which indeed led to a significant increase in yield and selectivity due to the high reactivity of the lithium dialkyl zincate enolate. Various 1,3-diketones 39 were prepared using this method with good yields and excellent enantioselectivities while only the trans

• %) but low trans/cis selectivity (Scheme 11). Organoaluminum reagents (Me3Al, Et3Al) were also compatible with the reaction, however, they gave lower yields than the corresponding organozincs. The authors have also shown that these products are suitable for forming [6,7]-bicyclic adducts. Conjugate

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• system was thus found to be compatible with the realization of this type of C‒H functionalization. This process led to a significant reduction of the reaction time compared to the batch, in particular by increasing the temperature to 200–250 °C, without significant losses of activity and selectivity

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• confirm the lack of selectivity during the cyclopropanation process with terminal alkenes, the reaction mechanism between the diazo reagent 5 and styrene as a model substrate in the presence of CuI catalyst was investigated by density functional theory (DFT) calculations (Table 2). In the first step, CuI

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• 10. The selectivity for the non-dehydrogenated coumarins 10d is not understood, but 10b likely does not undergo dehydrogenation because there is no formation of aromaticity to drive the reaction forward. When the bicyclic alkene is substituted unsymmetrically at the bridgehead position, the reaction

• ) [67]. Again, nitrogen-containing bicyclic alkenes proved difficult, as diazabicyclic alkenes produced the desired product in low yields while azabenzonorbornadienes failed to react entirely. It was found the introduction of a methyl group α to the boron on the dienylboronate caused the selectivity to

• be shifted to the 1,4-addition producing a cyclopentene product leading to the conclusion that the substitution pattern on the boronate ester played a significant role in the selectivity between 1,6-addition and 1,4-addition. The mechanism proposed by the authors initially begins in the same manner

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• trifluoromethylthiolation persist. In particular, the functionalization of a C(sp3)–H bond with a trifluoromethylthiolated moiety by transition-metal-catalyzed C–H activation remains a challenging task both in terms of reactivity and selectivity. In 2015, Besset reported the first C(sp3)–SCF3 bond formation of unactivated

• acrylamide derivatives [140]. Using the same directing group, a panel of α-arylacrylamide derivatives 39a–f was successfully functionalized with a high Z-selectivity (yields up to 98%, Scheme 18). Both, thermal reaction conditions (DMSO at 70 °C for 16 h) and microwave irradiation (100 °C using microwaves in

• only 1 h) turned out to be efficient in the process. α-Methyl- and α,β-dimethylacrylamides 39g and 39h were also functionalized. Furthermore, a series of β-substituted acrylamides 39i–m with various substituents readily underwent the trifluoromethylselenolation reaction with high selectivity in

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• necessary to give compound 17 in 85% yield after the two steps. Subsequent reaction of the aldehyde 17 following a modified Still–Gennari protocol [29] employing the phosphonate 18 gave the alkene 19 in 90% yield and high selectivity (cis/trans = 25:1). Removal of the silane group with TBAF furnished the

• proved to be important for the selectivity of the reaction, where significant cleavage of the benzyl group resulted when ethanol was the solvent of choice. Subsequent ester hydrolysis gave compound 112 (Scheme 22) [55]. In parallel, a Still–Gennari olefination using aldehyde 52 lead to the cis-alkene 113

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• processes in the pharmaceutical industry [1][27]. During continuous flow reactions, the target molecules can be produced with better purity, selectivity and in higher yields, as well as in consistent quality due to the precise parameter control, low volume ratio and small quantities. The temperature control

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• .19.24 Abstract A synthesis of 1,4-imino-ᴅ-lyxitols and their N-arylalkyl derivatives altered at C-5 is reported. Their inhibitory activity and selectivity toward four GH38 α-mannosidases (two Golgi types: GMIIb from Drosophila melanogaster and AMAN-2 from Caenorhabditis elegans, and two lysosomal types

• -deoxy-DIM was 3.5 times more potent toward AMAN-2 than DIM, their selectivity profiles were almost the same. N-Arylalkylation of 6-deoxy-DIM resulted only in a partial improvement as the selectivity was enhanced at the expense of potency. Structural and physicochemical properties of the corresponding

• . This explains why potent GMII inhibitors like swainsonine tend to lack significant selectivity. Therefore, the search for potent and selective GMII inhibitors is rather challenging. Over the last decades, almost all attempts at overcoming the selectivity challenge posed by swainsonine have not been

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• following criteria: position/stage of the key cyclooctane ring formation in the synthesis plan, the selectivity, and the opportunity for late-stage functionalization. Review 1 Metathesis: ring-closing metathesis and related methods The metathesis reaction, first discovered by serendipity in the 1950s, has

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• ) dimerization has some limitations, such as its controlling selectivity for intermolecular reactions in differently activated alkenes, and low reactivity. Han and co-workers [6] addressed the latter one by designing a substrate in which nucleophile functionality is also present in the Michael acceptor to

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

• synthesis by Taber that used dichromate as an oxidant [13] led to a less diastereoselective reaction furnishing the three ketones 9, 10, and 11 in a ratio of 36:2:5. The cis-conformation of the decalin backbone of 9 and 11 originates from the endo-selectivity of the Diels–Alder reaction and the boat

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• aromatic Grignard reagents which do not bear ω-magnesium alkoxide functionalities: in that case, EtOMgX can be used as an external additive to enhance the cross-coupling selectivity, in line with the alkyl–alkenyl and aryl–alkenyl cross-coupling methods discussed earlier (Scheme 5) [32]. The beneficial

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• [14], we had undertaken some preliminary investigations into the use of commercially available Diversinate™ reagents and showed the bicyclic nitrogen-rich core of Series 4 was amenable to this chemistry, with radical sulfinate substitution occurring with high-selectivity at C-8 and in respectable

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• isolated in 34% yield indicating that steric effects play a role during the oxidation step. We further wanted to investigate different arenes, but due to the lack of selectivity of the primary benzyl acetates in the Friedel–Crafts step, we were limited to para-substituted arenes, which unfortunately all

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• platforms [66], the group considered a system in which a photoexcited catalyst oxidatively cleaves a siloxycyclopropane with endo selectivity [67], leading to aryl–nickel capture and reductive elimination. Thus, when substrates 121 and 122 were photoirradiated with blue LED light at 45 °C in the presence of

• drastically the radical stability, nucleophilicity, and selectivity of 139 [73]. Furnishing of the common scaffold 130 can be carried out via an attack of intermediates of this type (e.g., 139) on Michael acceptors. Tosyl group deprotection of 130, followed by selenium anhydride oxidation and catalytic

• process, two major families of natural compounds are formed, namely the aporphine and the morphinandienone alkaloids. Mimicking the selectivity of the natural process in laboratory setups commonly proves tricky, producing an irreproducible yield of isomers for both classes. Recently, Felpin’s group

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• IC50 0.96 µM) and 4.85 µM (amphotericin B IC50 4.87 µM), respectively. Furthermore, digyalipopeptide A (1) produced IC50 values of 10.07 µM (ampicillin IC50 0.18 µM) and 10.01 µM (ampicillin IC50 1.53 µM) for Staphylococcus aureus and Shigella sonnei, respectively. The selectivity and toxicity profile

• of compound 1 was investigated using normal cell lines, macrophages RAW 264.7. When tested against normal macrophages, compound 1 gave an IC50 value of 71.32 μM. Selectivity indices (SI) were obtained by calculating the ratio of the IC50 in RAW 264.7 to the IC50 in the respective microbe and

• 10.01, 18.71, and 10.01 µM, respectively. The laboratory standard itself produced IC50 of 1.53 µM for Shigella sonnei, Shigella flexneri 1.76 µM, and Staphylococcus aureus 0.18 µM, respectively (Table 3). The selectivity and toxicity profile of compound 1 was also investigated using normal cell lines

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

• selectivity was achieved by chelation of the Sm(III) intermediate with hydroxy groups present on the structure. As the direct coupling with the A-ring precursor failed, a strategy to build this part was developed, starting with a sequence involving a protection of the alcohols as MOM ethers, lactone

• suitable starting material for the SmI2-promoted pinacol coupling, directed by the free hydroxy group, affording a complete selectivity in the formation of the 7-membered ring B. The synthesis of grayanotoxin III was then achieved by acetylation of the secondary alcohols, oxidative cleavage of the MOM

• , obtaining excellent selectivity in all cases. Alternatively, the same year, the authors published a vinyl radical cyclization occurring in presence of n-Bu3SnH, providing a stereoselective access to the bicyclo[3.2.1]octane unit corresponding to the CD rings [25]. Newhouse’s synthesis of principinol D In