A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• carbon, and one methyl carbon. A spin system H-6 (δH 6.85)/H-7 (δH 7.33) with an ortho-coupling constant (8.5 Hz) was observed using homonuclear correlation spectrometry (COSY). The heteronuclear multiple bond correlation (HMBC) cross-peaks from H-6 to C-2 (δC 112.4) and C-4 (δC 145.2), and from H-7 to C

• -1 (δC 173.8), C-3 (δC 151.0), and C-5 (δC 129.4) indicated that 1 has a 2,3-dihydroxybenzoic acid moiety (Table 1 and Figure 2a; Figure S3, Supporting Information File 1). A spin system H-9 (δH 4.58)/H2-10 (δH 3.54 and 3.23) was observed in 1H,1H COSY (Figure S5, Supporting Information File 1). The

• HMBC cross-peaks from H-9 to C-8 (δC 173.5) and C-11 (δC 173.4), from H2-10 to C-8 (δC 173.5) and C-9 (δC 53.6), and from H3-12 (δH 1.94) to C-11 (δC 173.4) indicated that 1 has a N-acetylcysteine moiety (Figure 2a). The HMBC cross-peak from H-10 (δH 3.23) to C-5 revealed the linkage between C-5 (δC

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

• Ruichen Lan Brock Yager Yoonsun Jee Cynthia S. Day Amanda C. Jones Chemistry, Wake Forest University, 1834 Gulley Rd., Winston-Salem, NC, 27109, USA 10.3762/bjoc.20.43 Abstract Kinetic studies on the intramolecular hydroamination of protected variants of 2,2-diphenylpent-4-en-1-amine were carried

• of alkenes remains challenging. Advances in asymmetric catalysis [2][3][4][5][6][7][8][9][10], C–N [11][12][13][14][15][16][17] and C–C functionalization [18][19] reveal opportunities, but harsh conditions and limited substrate scope present problems. Intramolecular reactions almost invariably

• protodeauration was not confirmed [27]. Follow-up studies in our lab revealed that the alkylgold intermediate (2a, Scheme 1) reacts significantly slower than observed rates for catalytic hydroamination, suggesting it is not a viable intermediate in the catalytic cycle [28]. It has been shown that C(sp2)-vinylgold

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• (C-2 to C-5), and a –CH–CH2–CH= moiety (C-8 to C-10) (Figure 2). HMBC correlations from H-4 to C-2 and C-6, from H-5 to C-1 and C-3, from 1-OH to C-2 and C-6, and from 6-OH to C-1, C-5, and C-14, led to the construction of the cyclohexane ring for 1, while HMBC correlations from H-9 to C-11, and from

• H-12 and H-13 to C-10 and C-11 constructed the isopentenyl group. Further HMBC correlations from H-15 to C-1, C-7, and C-8 connected the cyclohexane ring and isopentenyl from C-1 and C-8 via the non-protonated carbon C-7. The assignment of the thio-ether bond between C-8 and C-14 was supported by

• the HMBC correlation from H-14 to C-8, as well as the molecular formula combined with chemical shifts (δC 35.9, CH2-14, and δC 45.8, CH-8) [12]. Furthermore, HMBC correlations from the protons of methoxy to C-2 attached the methoxy group to C-2. The relative configuration of compound 1 was determined

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• significant pharmaceuticals [lubiprostone (constipation), maraviroc (HIV), tafluproct (anti-inflamatory), ledipasvir (hepatitis-C)] and agrochemicals [isopyrazam (fungicide), riodipine (calcium channel blocker), primisulfuron-methyl (pesticide)] owe their enhanced bioactivity, in part, to the presence of

• rotated to maximize the distances between the lone pairs of the electron-rich fluorine and oxygen atoms. Usually, one of the fluorine atoms lies in a syn orientation to an oxygen (e.g., 3f has an F–C–C–O dihedral angle of 15.6°) creating a dipole. This dipole appears to aid crystal packing by forming weak

• extraction. Indeed, attempts to grow a single crystal of 5e from a mixture of EtOH and water led to the isolation of the corresponding gem-diol (Figure 3). There are very few examples of organic structures containing a C(OH)2–CF2–C fragment in the CCDC and only three acyclic examples (CSD 5.43 (Nov. 2021

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• 1b. Wherein various alkyl and aryl olefins, including those that contain Lewis basic esters, carbamates and amines or α-branched moieties, may be used in efficient and exceptionally Z-selective cross-metathesis reactions [6][7][8]. A few years ago, some publications devoted to the cleavage of the C–F

• the formation of the corresponding olefin [12]. Another area of application of olefins 1a,b is based on C=C double bond addition reactions. As early as 1968, Atherton and Fields showed that (Z)- and (E)-butenes 1a,b reacted with diazotrifluoroethane to give 3,4,5-tris(trifluoromethyl)pyrazoline [13

• completion of the reaction the mixture of isomers 3a,b was separated from the water phase and distilled at 55 °C. Further increase in the amount of KOH led to the elimination of the second mole of HBr with the formation of hexafluorobut-2-yne (4). By controlling the course of the reaction by the 19F NMR

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• arm in an adjacent peptidyl carrier protein (PCP). The amino acid loaded on the PCP then undergoes coupling with the amino acid loaded on the downstream PCP in the condensation (C) domain. Finally, the linear peptide on the PCP in the last module is either hydrolyzed or cyclized by a thioesterase (TE

• purified recombinant GrsA, inhibitor 5 moderately inhibited labeling at 100 µM. Finally, we investigated whether the inhibitors could penetrate cells and inhibit intracellular GrsA labeling in A. miglanus ATCC 9999. In this study, A. migulanus ATCC 9999 cells were grown at 37 °C in YPG medium for 24 h

• penetrate cells. The application of this new scaffold to NRPS inhibitors involved in the production of virulence factors could thus facilitate the development of new antibiotics. Biosynthesis of gramicidin S. Modules comprise the PCP, A, E, C, and TE domains. PCP, peptidyl carrier protein; A1, ʟ-Phe

Enhanced host–guest interaction between [10]cycloparaphenylene ([10]CPP) and [5]CPP by cationic charges

• Eiichi Kayahara,
• Yoshiyuki Mizuhata and
• Shigeru Yamago

Beilstein J. Org. Chem. 2024, 20, 436–444, doi:10.3762/bjoc.20.38

• , [10]CPP⊃[5]CPP2+. While the same host–guest complex consisted of neutral CPPs, [10]CPP⊃[5]CPP, was already reported, the cationic complex showed an about 20 times higher association constant in (CDCl2)2 at 25 °C (103 mol L−1). Electrochemical and photophysical analyses and theoretical calculations

• + and neutral CPP was first examined by adding a solution of [5]CPP2+[B(C6F5)4−]2 in CD2Cl2 to a mixture of [8]-, [9]-, [10]-, [11]-, and [12]CPPs in CD2Cl2 at 25 °C (Figure 2a). In the 1H NMR spectrum of the resulting mixture, only the signals of [10]CPP and [5]CPP2+ shifted downfield by about 0.44 ppm

• complex was also formed by mixing a 1:1 mixture of radical cations of [5]- and [10]CPP, [5]CPP•+ (SbCl6−) and [10]CPP•+ (SbCl6−), respectively (Figure 1c, path C). The observed results can be explained by two reasons; one is the oxidation potentials of [10]- and [5]CPPs. In sharp contrast to linear π

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

• -catalyzed annulative π-extension of 1,8-dibromonaphthalene for the preparation of fluoranthenes in a single operation has been investigated. With specific arenes such as fluorobenzenes, the Pd-catalyzed double functionalization of C–H bonds yields the desired fluoranthenes. The reaction proceeds via a

• palladium-catalyzed direct intermolecular arylation, followed by a direct intramolecular arylation step. As the C–H bond activation of several benzene derivatives remains very challenging, the preparation of fluoranthenes from 1,8-dibromonaphthalene via Suzuki coupling followed by intramolecular C–H

• activation has also been investigated to provide a complementary method. Using the most appropriate synthetic route and substrates, it is possible to introduce the desired functional groups at positions 7–10 on fluoranthenes. Keywords: catalysis; C–H bond functionalization; direct arylation; fluoranthenes

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

• prostate cancer. The same apoptotic function can be observed in colon and pancreatic cancer, since BIMs (specifically DIM-C-pPhOCH3 (5)) can act as a Nur77 (Nuclear Receptor 4A1) antagonist, which modulates the life cycle of cells [6]. The correlation between lower lung cancer risk and the consumption of

• :0.05, under solvent-free conditions at 50 °C for 50 min, the product was obtained in 90% yield. To emphasize the role of DBDMH, when the reaction was performed without DBDMH, no product was observed. The generality of this protocol was also tested by employing various aromatic aldehydes, which formed

• mixture was heated at 50 °C. The generality of this approach was also excellent with substituted ketones, aldehydes and indoles, all forming the respective BIMs in yields ranging from 65–98% with ketones displaying the lowest reactivity, requiring up to 12 h for reaction completion. Thus, this protocol is

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• -hydroxyphthalimide (NHPI) esters (3) have emerged as convenient alternatives to Barton esters (Scheme 1) due in part to their ease of synthesis and greater stability (N–O BDE ≈ 75 kcal/mol) [28]. Their use as radical precursors was first described by Okada and colleagues in 1988 [29], who showed that C(sp3)-centered

• electronically excited substrate (*S) through an energy transfer (EnT) mechanism (path c). In addition to these mechanistic blueprints, the formation of charge-transfer complexes involving NHPI esters, as well as examples of photoinduced transition metal-catalyzed activation will be discussed. Depending on the

• isonicotinate tert-butyl ester) in C(sp2)-borylation methods under photochemical and thermal conditions, respectively [65][66]. The activation of NHPI esters through EDA complex formation is also possible by employing a catalytic donor species, which enables a range of redox neutral transformations. In 2019

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• short-term heating of the melted reactants at 220–250 °C is described, and the compounds were characterized by means of single-crystal X-ray crystallography, NMR, UV–vis, and IR spectroscopy, as well as cyclic voltammetry. The reaction with o-amino-, o-hydroxy-, and o-mercapto-substituted arylamines

• ][12]. At the first stage, this reaction follows one of three possible reaction pathways, including Schiff base formation (attack at the C(3) center), Michael addition at C(1), or nucleophilic substitution (SNH) at the C(2) center [13][14][15]. Most readily used is the pathway involving carbonyl–amine

• highly basic amines (Scheme 1) [6]. The choice for one of the other two possible reaction pathways (nucleophilic additions to either the C(1) or C(2) center) critically depends on the electrophilicity. Figure 1 shows the distribution of electronic density in 6,8-di-tert-butyl-3H-phenoxazin-3-one (1

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains

• Sharmila Neupane,
• Marcelo Rodrigues de Amorim and
• Elizabeth Skellam

Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32

• 2 was determined by Marfey’s method. A biosynthetic gene cluster (BGC) encoding unguisins B and J was compared to characterized BGCs in other Aspergillus sp. Since the unguisin family of heptapetides incorporate different amino acid residues at different positions of the peptide, the A and C domains

• of several catalytic domains organized into modules. Typically, a module possesses an adenylation (A) domain for selecting and activating amino- or keto acids, a thiolation (T) domain for shuttling intermediates between catalytic domains, and a condensation (C) domain that catalyzes amide or ester

• facilitate release from the NRPS. Of the fungal NRPS studied to date, many appear to have some tolerance for the range of amino acids incorporated by the A domains and the C domain has been highlighted as a gatekeeper [13]. Here, we describe the isolation of unguisin B, and a new congener named unguisin J

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• aligned the individual units of the tandem repeat CBM13 domains, indicated by the N-terminal (34-158) and C-terminal units (162-286) and compared those to the domains of ricin (Figure 1b). R-type lectins have a characteristic Q-x-W structural motif close to their binding site, which is highly conserved

• [21]. We report that CMA1 largely follows this trend, with three such binding sites in both N- and C-terminal domain, albeit with imperfect overlap. Based on the location of the known binding pocket of the R-type lectin ricin and the respective sequence conservation in CMA1, we postulate binding sites

• around W63 for the N-terminal domain and F273 for the C-terminal domain of CMA1. As binding specificities of melon lectins in general (beyond chitooligosaccharides), and CMA1 in particular, are still unknown, we set out to measure, quantify, and understand the glycan-binding properties of CMA1 in depth

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• performances. Since the synthesis of π-CPCs involving as final step the elimination of C-based molecules, i.e., a retro-Diels–Alder reaction or a decarbonylation, has already been thoroughly reviewed in the past years [4][5][9][10][11][12], this review focuses on the late-stage extrusion of chalcogen fragments

• recognized as valuable synthetic tools in organic chemistry [54], with the most famous S-extrusion process to generate new C–C bonds probably being the Ramberg–Bäcklund reaction [55]. In the case of heteropines, chalcogen extrusion leads to a six-membered ring via the intramolecular formation of a C–C bond

• thiepine precursor 3a exhibited a mass decrease at 300 °C in agreement with the expected elimination of sulfur to yield almost quantitatively the corresponding PBI 6a. Its sulfoxide analogue 4a exhibited higher thermal reactivity, with the loss of SO identified at lower temperature (225 °C). As a proof of

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• different reaction times revealed that the reaction was complete within 2 hours (Table 1, entry 14). We then explored the effect of the temperature on the reaction and found that 25 °C was the most suitable temperature, resulting in a 91% yield (Table 1, entry 14). Lower temperatures of 0 °C and 10 °C led

• to decreased yields of 24% and 49%, respectively (Table 1, entries 16 and 17). Increasing the temperature beyond 25 °C resulted in the formation of impurities and a decrease in the yield of the target compound (Table 1, entries 18 and 19). Finally, the optimal reaction conditions were determined as

• follows: 1a (1.0 mmol), 2a (1.5 mmol), Et3N (2.0 mmol), in acetonitrile at 25 °C with stirring for 2 hours (Table 1, entry 14). With the optimized reaction conditions in hand, we next investigated the scope of the current reaction (Scheme 2). As shown in Scheme 2, a series of α-halogeno hydrazones 2b–l

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• (fulleroid) derivatives. The aim is to shed light on the regioselectivity of the process through both experimental and computational approaches. In addition, the photooxidation of one of the C–C double bonds in the synthesized bis(fulleroids) affords open-cage C70 derivatives having a 12-membered ring

• cages. However, in other cases, some of the bonds between the C atoms of the cage are broken and the cage is opened. The first example of an open-cage fullerene was reported in 1995 by Hummelen, Prato, and Wudl [21] through the reaction of C60 with azides followed by photooxygenation. Since then, many

• heating at 90 °C for 4 hours. The crude reaction mass obtained with these conditions was then purified by column chromatography (toluene). After eluting unreacted pristine C70, a dark reddish fraction was isolated and analyzed by HPLC. A major peak was observed at a retention time of 17.5 minutes, which

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• ; Introduction Proton-coupled electron transfer (PCET) enables the generation of various radical species under ambient conditions (Figure 1, top) [1]. In PCET processes, hydrogen bond formation between weak bases and acidic X–H bonds (X = N, O, C) is a key step, which is followed by concerted proton- and

• electron-transfer to give the corresponding radical species through oxidative X–H bond cleavage. One such species is the amidyl radical, which is broadly synthetically useful as a nitrogen source in hydroamination reactions and as a hydrogen atom transfer (HAT) reagent for remote C–H activation [2][3][4][5

• avoided [9]. The initial aim of this study was the electrochemical generation of an amidyl radical as a HAT source for the synthesis of 1’-C functionalized nucleosides via the generation of an anomeric radical species from uridine derivative 1 (Figure 1, bottom) [10]. Although the HAT reaction failed

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• ][5][6][7][8][9][10] have been extensively utilized as readily accessible synthetic building blocks in organic synthesis, particularly in the ipso-functionalization of C–S bonds. Of the sulfonium salts, organothianthrenium salts exhibit distinct structural properties and reactivities, thereby offering

• regioselectivity. Significant advancements in the synthesis of arylthianthrenium salts have prompted a growing interest in their utilization as versatile precursors for the conversion of C–H bonds in arenes into C–C/X bonds through transition-metal-catalyzed cross-coupling processes [12][13][14][15][16][17][18][19

• -stage C–H functionalization of arenes, Wickens’s group has introduced an oxidative alkene aziridination strategy that relies on thianthrenation of an alkene under electrochemical conditions [27]. Subsequently, cyclopropanation, [28] aziridination, [29] allylic C–H functionalization, [30][31] transition

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• of KMnO4 at 100 °C. The variation of the nucleophile did not give positive results either. For example, the replacement of dimethylamine with higher-boiling piperidine and n-butylamine or using liquid ammonia, which is highly reactive in such transformations, dipyridoacenaphthene 5 still returned

• unchanged, although quinoline and its derivatives are easily aminated under the same conditions [17]. No interaction occurred under the conditions of the Chichibabin reaction in an attempt to aminate compound 5 with sodium amide in N,N-dimethylaniline at 140–155 °C for an hour. Thus, quinoquinoline 5

• of quinoquinolines, their planar structure, and very easy coordination to acidic and electrophilic sites (including water [15][22] or the C–H bond of chloroform [11]) almost always lead to co-crystallization. For example, there is no such crystallographic information for quinoquinoline 3 itself. In

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• towards indigo and its derivatives have been recently reviewed in detail by Hecht and Huang [9]. Strucutre and photophysical properties of indigo Indigo dye is blue crystalline powder, which starts to melt at above 390 °C and sublimes in vacuum at above 170 °C [2]. In 1980, it was discovered that indigo

• melting point of indigo is bifurcated intra- and intermolecular hydrogen bonding [11], and face-to-face π–π stacking of parallel aromatic rings (Figure 2) [12]. Single crystal X-ray diffraction analysis showed that the indigo molecule is almost planar and exists in the E-conformation. The central C=C bond

• and C=O bonds of the indoxyl groups are somewhat longer than typical double bonds of these types (Figure 3). On the contrary, the C–N bonds in indigo are much shorter than the single C–N bond in pyrrolidine, while the lengths of the C–C bonds in the fused benzene rings are approximately the same as in

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• conditions such as transitioning from 0 °C to room temperature and extending the reaction duration from 3 to 24 hours, we did not observe the anticipated enhancements (51% yield, entry 1, Table 1). This trend persisted when we attempted glycosylation between C6-acetylated MurNAc derivative 2b and 1a, where

• , followed by in situ re-acetylation of the C2-amino group and C6-alcohol with acetic anhydride, resulting in the formation of disaccharide 4 in a one-pot fashion. The anomeric benzyl protecting group in disaccharide 4 was then removed via a Pd/C-catalyzed hydrogenation reaction, producing a mixture of α/β

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• reacts with the copper catalyst generating the Cu-carbene intermediate B, which undergoes nucleophilic attack by acetonitrile to form the intermediate C. Subsequently, nucleophilic addition of benzoic acid to intermediate C affords the acetimidic anhydride D with the release of CuI catalyst for the next

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• enantioselectivity decreased when the reaction temperature was reduced to 0 °C (Table 2, entry 7). With the optimal reaction conditions in hand, the substrate range of 2-alkynyl-3,3-difluoro-3H-indoles 1 for this transfer hydrogenation reaction was investigated (Scheme 2). Fluoro-, chloro-, and bromo-substituted 3,3

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• (DBDAPs) is disclosed in this article through a palladium and copper-catalyzed amination (Buchwald–Hartwig (B–H) or Chan–Lam (C–L)) followed by a palladium-catalyzed intramolecular aminocarbonylation with Mo(CO)6 as CO surrogate (to avoid toxic CO handling) of readily available o-phenylenediamines and

• either 1,2-dibromobenzene or 2-bromophenylboronic acid. The 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepinone could be synthezised in good yield using a sequential catalytic procedure, using both C–L and B–H approaches. Gratifingly, the use of the C–L reaction was more impressive, and afforded the

• review in 2018 focused on a variety of routes to these compounds [8]. The well-known Buchwald–Hartwig (B–H) and Chan–Lam (C–L) reactions have proven to be highly useful procedures that allow the step-economical synthesis of diverse biologically relevant heterocycles through C–N bond formation [9]. These

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• concentration ranges featured by different supramers. However, a more careful examination of the data clearly suggests the presence of two concentration ranges, where the differences in SR values are statistically significant (see the grey boxes in Figure 1a): the high concentration range (c = 0.15–0.20 mol·L−1

• ), where SR values are close to each other ([α]D28 = −102.1 ± 0.9 deg·dm−1·cm3·g−1) and the low concentration range (c = 0.02–0.10 mol·L−1), where the SR values are noticeably different from those in the high concentration range ([α]D28 = −108.3 ± 1.7 deg·dm−1·cm3·g−1). Similarly, two ranges of

• concentrations exist in solutions of sialyl donor 2 in MeCN (see the grey boxes in Figure 1b): the high concentration range (c = 0.085–0.15 mol·L−1), where [α]D28 = −109.3 ± 1.8 deg·dm−1·cm3·g−1) and the low concentration range (c = 0.02–0.05 mol·L−1), where [α]D28 = −102.5 ± 0.9 deg·dm−1·cm3·g−1. According to