Search results
Search for "intermediate" in Full Text gives 2122 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides
Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131
- Program, Taiwan International Graduate Program (TIGP), Academia Sinica, Taipei 115, Taiwan 10.3762/bjoc.21.131 Abstract Pyruvate ketal is a biologically essential moiety due to its key role as an intermediate in metabolic pathways, serving as a key precursor for the synthesis of various essential
- to synthesize a pyruvate ketal-containing PS A1 precursor associated with the commensal anaerobic bacteria capsule (Scheme 1) [7][8][9][10][11]. The target structure was β-ᴅ-Galf-(1→3)-α-ᴅ-Gal-(1→3)-β-ᴅ-Gal. This molecule acts as a critical intermediate for synthesizing various O4-linked PS A1
Influence of the cation in hypophosphite-mediated catalyst-free reductive amination
Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130
- reaction medium, thereby preventing their reduction. This fact and the result of the control experiment where Schiff base was used as a starting material (Scheme 3a) demonstrated that Schiff base was not an intermediate in the developed reaction. The reactions between carbonyl compounds and secondary
- amines proceeded forming products in moderate to high yields. In this process enamine can be the intermediate. Therefore, enamine was tested in the control experiment and the corresponding product was obtained in moderate yield (49%). To validate the experiment with enamine the reductive amination with
- equal amounts of the corresponding carbonyl compound and amine was carried out and the product was obtained in 69% yield (Scheme 3b). Therefore, enamine could be considered as an intermediate or resting state of the reaction, but more likely the real intermediate is an iminium cation or hemiaminal. To
Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO
Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127
- is the retrosynthetic analysis for the key intermediate 1, which can reach the final compound VI via chlorination and demethylation [19]. Target molecule 1 can be accessed by decarboxylation reaction from compound 13, prepared by an intramolecular Heck reaction between the β-ketoester and the vinyl
Transition-state aromaticity and its relationship with reactivity in pericyclic reactions
Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125
- ) of the butadiene + ethylene reaction proceeds with a lower barrier (up to 7 kcal/mol) than the corresponding stepwise pathway leading to a diradical intermediate (Scheme 1a) [19][20]. Similar preferences for concerted pathways over stepwise mechanisms were also found for dipolar cycloadditions and
- [81]. From a mechanistic point of view, this process involves the initial formation of a bent-allene intermediate, which leads to the final reaction product via hydrogen shifts (Scheme 2) [82]. The so-called Bergman cyclization of cis-3-hexene-1,5-diynes [83][84], which is suggested to proceed through
3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles
Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123
- intermediate formation of free radical species [9]. A similar reaction of N-acetyl substituted indole 9c produced [3 + 2] cycloaddition products 12 in even lower yield (4%). However, the main reaction product turned out to be unstable compound 13, which, nevertheless, was isolated in 40% yield as a single
- mechanisms of the formation of azirindine 16 under Ni(II)- and Cu(I)-catalysis. Oxidative dimerization of non-aromatic cyclic enols has been previously observed in their reactions with 3-arylazirines catalyzed by Cu(I) and Cu(II) complexes and was attributed to the recombination of intermediate free radicals
Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins
Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118
- bioactive fragments into a single molecule through a spacer. An alternative strategy of combining heterocyclic pharmacophores is to incorporate them into a spiro-jointed structure that lacks any intermediate link between the active parts [17]. Despite the fact that these strategies share numerous
General method for the synthesis of enaminones via photocatalysis
Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116
- -mediated reaction for the synthesis of enaminones from 3-bromochromones (Scheme 1D). Initially, a Ni(II)-catalyzed hydroamination protocol affords the intermediate 2-amino-3-bromochromanones, which upon photocatalytic dehalogenation and subsequent opening of the heterocyclic ring provide the corresponding
- semipreparative scale for the reaction of 3-bromochromone (7a, 5.0 mmol) to afford enaminone 9a in a 68% isolated yield (Scheme 3). In terms of the reaction mechanism, TEMPO completely inhibited the reaction, implying the possibility of a radical intermediate in the reaction (Scheme 4A). Moreover, the TEMPO
Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones
Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113
- terminal S‒CH2 position, leading to the formation of the sulfonium cation 11 and the delocalized heterocyclic anion 12 (Scheme 6). In the next step, competitive addition of both intermediate species yields either thioaminals 9 or dithioacetals 10. However, a slow isomerization of the thermodynamically less
Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids
Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111
- pathway of brassicicenes in Aspergillus oryzae and harnessing the promiscuity of a cytochrome P450 from the biosynthesis of fusicoccin A (Figure 1b). A key intermediate, brassicicenes I (5), was further used to achieve the collective synthesis of alterbrassicicene E (6), brassicicenes A (7) and R (8
- cotylenin A and cotylenol (Figure 3a). Oxidation of brassicicene I with Dess–Martin reagent afforded intermediate 9 in 92% yield. The tertiary hydroxy group of compound 9 was further protected with a TMS group to provide compound 10 in 90% yield, a key intermediate in the synthesis of cotylenol and
- oxaziridine [25], furnishing intermediate 18 in 72% yield. After deprotection of the TBS and TES groups, brassicicene R (8) was obtained in 70% yield. Therefore, alterbrassicicene E (6) and brassicicenes A (7) and R (8) were synthesized from brassicicene I over 4 or 5 chemical steps. Conclusion In summary
Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides
Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110
- resulting aryl radical is subsequently captured by an isonitrile molecule, forming an imidoyl radical intermediate X1. The intermediate X1 facilitates the reduction of the Ru(III) species back to Ru(II) thereby completing the photoredox cycle, with the formation of the cationic intermediate X2. We propose
Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper
Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108
- with the vessel pressurised under nitrogen (Table 2, entry 7). Under these conditions, the yield was 58%, demonstrating the superiority of an open vessel in a multimode cavity for this reaction. Since Cu salts facilitate both the nucleophilic attack of piperidine on benzoxazole to form the intermediate
- contrast, the presence of Cu facilitated the conversion of the intermediate to the desired aromatic benzoxazole 2a, demonstrating copper’s dual role as a Lewis acid in enhancing nucleophilic attack, and as an efficient catalyst for ring-closing oxidative rearomatisation. Of the conditions tested, the use
- of CuCl2 in toluene showed limited effectiveness, achieving 82% conversion but only a 28% yield of the final product. The remaining resulting mixture included 35% of the intermediate 2a-o and 19% of the hydrolysed product 2a-o-hydrol. However, the reaction performance in acetonitrile improved
Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds
Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105
- , populating both KE and KK, which undergo ground-state PT to E and K, respectively. Therefore, it is crucial to have the intermediate keto tautomers KE and KK higher in energy in the ground state, comparing to the paired terminal E and K, respectively, in order to provide efficient switching. The additional
Oxetanes: formation, reactivity and total syntheses of natural products
Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101
- /RPC mechanism starts with a single-electron oxidation of the cobalt catalyst followed by a reaction with the siloxane to generate a cobalt–hydride complex. Subsequent hydride transfer to the alkene produces radical pair 23 which collapses to alkylcobalt intermediate 24. Another single-electron
- intramolecular E2 elimination. Finally, the importance and power of the intramolecular Williamson etherification has also been demonstrated by the kilogram-scale synthesis of oxetane intermediate 41, which is a key intermediate in the preparation of the previously mentioned IDO1 inhibitor 2 (Scheme 9) [16
- , and 6-endo cyclization pathways – this may be attributed to precoordination of the Cu(I) catalyst to the alkoxide, which facilitates oxidative addition into the C–Br bond and results in the formation of a favorable five-membered Cu-containing intermediate [48]. Ten years later, while developing the
Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer
Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100
- it into the byproduct 46 and generating a carbon-centered radical 62. Species 62 is trapped by heteroarene 60, leading to the formation of the intermediate 63. This intermediate 63 undergoes SET and proton transfer with the assistance of O-anion 64 and the Br-5CzBN+• radical cation, delivering the
- abstracts a hydrogen atom from substrate 1 through HAT, producing an α-amido-acridinyl radical intermediate 92 and a substrate-derived carbon-centered radical 4. Radical 4 undergoes regioselective addition to the acceptor, forming transient radical adduct 93. A concomitant SET from 92 to 93 generates a
Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes
Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99
- -known Ziegler–Hafner azulene synthesis [35]. The key step in this method involves the synthesis of the intermediate pentafulvene, which is subsequently cyclized to yield the target azulene. An example of this strategy is the synthesis of the azulene-embedded isomer of benzo[a]pyrene which was reported
- acenes from anthracene to pentacene (57a–d) in rather low yields (16–38%). The synthetic pathway leading to the hexacene isomer 60 was more complex due to the high reactivity of intermediate pentacenes. Instead, pentacene-6,13-dione 58 was subjected to the reaction with di-n-butylacetylene (56) giving
- constructed by condensation of dialdehyde 160 with compounds 161–163 yielding diketones 164–166. Next, diketones 164–166 were subjected to nucleophilic addition reaction by lithiated triisopropylsilyl (TIPS) acetylene, followed by SnCl2-mediated reduction of the intermediate diols. Finally, azulene-embedded
Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents
Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98
- radical A. This is followed by the conversion of a substrate containing C(sp3)–H bonds adjacent to an oxygen atom into an alkyl radical intermediate B. The alkyl radical intermediate then adds to the C=C bond of N-arylacrylamide, generating a second alkyl radical intermediate C, which undergoes
- intramolecular cyclization to form a benzene ring radical intermediate D. Finally, hydrogen abstraction from the radical intermediate by Fe3+(OH) leads to the formation of oxindole compounds 5. A similar reaction was reported by Liang’s group in the same year, as shown in Scheme 4. The study introduced a metal
- intermediate 12. Subsequent intramolecular cyclization and oxidative aromatization lead to the final isoxazoline-featured oxindole 9. In 2017, Li’s group reported an oxidative divergent bicyclization of 1,n-enynes through α-C(sp3)–H functionalization of alkyl nitriles using a Sc(OTf)3 and Ag2O system (Scheme 7
Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents
Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97
- deprotonation, followed by chloride elimination/neutralization from the zwitterionic tetrahedral intermediate 5 to give the target molecule 1. The standard protocol for the synthesis of (hetero)aroyl-S,N-ketene acetals 8 from (hetero)aroyl chlorides 6 and 2-methylbenzothiazolium salts 7 employs a twofold excess
- of an amine base in a binary 1,4-dioxane/ethanol mixture. Ethanol was used as a cosolvent to ensure solubility of the polar intermediate according to the mechanistic rationale (Scheme 2) [5][6]. Although, a broad scope of diversely substituted (hetero)aroyl-S,N-ketene acetals 8 was obtained (111
- addition, since condensations are affected by the bimolecular addition as an elementary step, special attention to the concentration of the nucleophiles has to be paid. According to Mayr’s nucleophilicity scales [8][9][10], a nucleophilicity parameter N for the specific S,N-ketene acetal intermediate 4 can
Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates
Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96
- radicals and product 3 can be described by several pathways. The direct oxidation of 2 by Cu(II) A leads to the formation of P-centered radical E and Cu(I) B. Under air atmosphere, the formed Cu(I) species B can react with molecular oxygen resulting in the formation of peroxycopper intermediate C [75][76
- hydroperoxide transfer from copper complex D with the formation of intermediate H and, therefore, regenerating Cu(I) B. Alternatively, the latter can be formed by oxidation of benzylic radical G with the formation of carbocation I. However, given that in the absence of oxygen the β-ketophosphonate was formed
Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups
Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94
- directing group facilitates this step as it stabilizes the complex through coordination to the Pd atom, thereby lowering the reaction barrier. A depiction of the CMD step is shown in Figure 1. Upon C–H bond breaking, the Pd atom moves into the plane of the aromatic ring, forming a palladacycle intermediate
- and carboxylic acid. The palladacycle intermediate can undergo further (coupling) reactions and form a variety of products via reductive elimination. In previous studies, the rate- and regioselectivity-controlling step was identified as the formation of the palladacycle [5][6][7]. The regioselectivity
- be predicted by calculation and comparison of the relative energies of the proceeding palladacycle intermediate, as postulated in the Bell–Evans–Polanyi (BEP) principle [10][11]. Focussing on the intermediates allows for easier automation of the calculations since a minimum instead of a saddle point
A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones
Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92
- reaction followed by the cleavage of the alkyl group to give intermediate II as a free amine. Annulation of II with CDI gave product B which is an HIV reverse transcriptase inhibitor (Scheme 1B) [17]. We have reported a three-component [3 + 2] cycloaddition followed by IMDA reaction for making heterocyclic
- compounds [18]. Presented in this paper is a new synthetic route involving GBB, N-acylation and IMDA reactions for making intermediate III followed by dehydrative re-aromatization to give imidazopyridine-fused isoquinolinones C (Scheme 1C). Results and Discussion Following the reported procedures [10], the
- intermediate 7, the carbonyl oxygen interacts with AlCl₃, enhancing the electrophilicity and promoting the rearrangement to form stable oxonium ions. The removal of water from 7 is facilitated by protonation, producing reactive carbocations which undergo dehydrative aromatization to produce products 8
Synthetic approach to borrelidin fragments: focus on key intermediates
Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91
- approach for constructing Morken’s C2–C12 fragment In 2019, Uguen and co-workers introduced a strategy to assemble Morken’s C2–C12 intermediate 20 [41]. Their approach utilized iterative base-catalyzed condensation of sulfone compounds with epoxides. As illustrated in Scheme 1, the monoalcohol 20 was
- . Intermediate 25 was prepared through TBDMS protection and desulfonylation of 24, itself derived from the condensation of epoxide 23b and sulfone 27. The precursor 27 was synthesized from Roche ester 29 via a sequence of steps, including reduction, three-carbon homologation, and enzymatic desymmetrization. An
- 94% yield. Like 40, iodination of ent-40 gave crystalline product ent-42, and its structure was confirmed by XRD crystallography. The intermediate ent-40 was then subjected to the same tosylation/thiolation/oxidation sequence used for the 40 to 41 conversion, yielding ent-41 in comparable yield (82
A versatile route towards 6-arylpipecolic acids
Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88
- aryl modifications in C6 position by utilising the chiral pool of a non-proteinogenic amino acid in combination with transition metal-catalysed cross-coupling reactions. Moreover, we present an in-depth NMR analysis of the key intermediate steps, which illustrates the conformational constraints in
- a key intermediate product. This late-stage approach was previously described by us while utilising Suzuki–Miyaura or Sonogashira–Hagihara cross-coupling reactions to generate pipecolic acid derivatives with alkynyl substituents in the C6 position [35]. Here, we present a robust synthetic route to
- to investigate how the configuration of the stereocenter in C2 position influences diastereoselectivity. In the first approach, NaBH3CN was used under acidic conditions to reduce the acyliminium intermediate formed from the N-acyl enamine upon protonation at C5, while in the second approach
Recent advances in synthetic approaches for bioactive cinnamic acid derivatives
Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85
- amidation in 5 min reaction time via the formation of the isolable enol ester intermediate 23 (Scheme 8A). Similarly, Feng and co-workers (2019) studied one-pot two-step esterification of cinnamic acid (7) by applying electrophilic sp carbon center of methyl propiolate (25) as the coupling reagent via in
- it with a triflate surrogate, 4-acetamidophenyl triflimide (AITF), to generate the intermediate reactive acyl triflic anhydride 28 which afforded the corresponding amide 27 in good yield (Scheme 9) [41]. On the other hand, Braddock and co-workers (2022) employed methyltrimethoxysilane (MTM) to
- acid (7) by using trichloroisocyanuric acid/triphenylphosphine (TCCA/PPh3) assisted by ultrasound to give the corresponding amide 34 in good yield (Scheme 12) [44]. Herein, PPh3 attacks chloride atoms in TCCA to subsequently generate phosphonium intermediate 35, followed by the formation of reactive
Recent total synthesis of natural products leveraging a strategy of enamide cyclization
Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81
- acetylcholinesterase (AChE) inhibitory activities [18]. In the presence of a catalytic amount of PPh3AuCl and AgSbF6, the enamide–alkyne cycloisomerization of bromo-substituted alkyne 8 proceeded via a 5-endo-dig cyclization to afford tricyclic compound 10 through the formation of iminium intermediate 9. The azepane
- cyclopentane ring, dihydroxylation, and oxidation of the diol to a diketone, produced intermediate 25 in its enol form. From this common intermediate, regioselective etherification at the less hindered position formed an enol ether. Final reduction of both the amide and the ketone using alane completed the
- 0.4% amount of cat. 1 provided adduct 30 in 72% yield with 92% enantioselectivity, and the reaction could be scaled up to decagrams. Subsequent decarboxylation and recrystallization of the resulting ketone 31 yielded an enantiopure product (99% ee), which serves as a versatile intermediate for the
Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline
Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79
- , Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary 10.3762/bjoc.21.79 Abstract A new total synthesis of the β-carboline alkaloid brevicarine is disclosed. The synthesis was carried out starting from an aromatic triflate key intermediate, allowing the introduction of various substituents into
- salt for further confirming their structures. A new synthesis of the related alkaloid brevicolline was also attempted from the same intermediate. However, after successful coupling of β-carboline with N-methylpyrrole, the trials to saturate the pyrrole ring under various conditions led to unexpected
- , versatile key triflate intermediate 3, which allowed the introduction of substituents attached by a C–C bond to position 4 of the β-carboline scaffold by cross-coupling reactions. Sonogashira reaction of compound 3 with N-(3-butynyl)phthalimide (4) led to coupled compound 5. Cleavage of the phthalimide
Other Beilstein-Institut Open Science Activities
