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

• + ions [34]. Because of the synergistic combination of Q[8], SQ2 and Hg2+ ions, it shows fluorescence quenching. Cong's group found that Q[7] can encapsulate the benzimidazole part of N-(2-benzimidazolylmethyl)-N,N-bis(2-pyridylmethyl)amine cation (BIBPA+) to construct a host–guest fluorescent probe. The

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

• demonstrated that the reaction in the presence of cationic zirconium complexes derived from zirconium dibenzyl complexes bearing tridentate [ONO]-type amine-bridged bis(phenolato) ligands and [Ph3C][B(C6F5)4] (Scheme 5), gave rise to ortho-selective C–H alkylated pyridines 19 and 21. It was observed that the

• 205 were accessed in moderate to excellent yields and also naphthyridine derivatives (205k and 205l) were synthesized. In the proposed mechanism, the initial deprotonation of HNBn2 by Ln[N(TMS)2]3 provided the lanthanide amide. Activation of the vinyl-substituted pyridin-3-amine 204 by the lanthanide

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• MeCN undergoes a ring transformation [1][2] to give 2-phenyl-5-(2-aminophenyl)-4-hydroxy-1,3-thiazole (17') (Scheme 7) under kinetic control, the analogous intermediary hydroxythiazole 7a (Scheme 3) does not decompose into analogous thiazole 7a' due to much worse nucleofugality of the leaving amine

• elimination of the water molecule from 7a,b to give 8a,b to be preferred over the ring opening giving 7a,b'. The worse leaving ability of aliphatic amine nitrogen is also manifested in a much lower yield of thiazole 13 from salt 12b which preferably undergoes elimination, while salt 12a having a much better

• ). α-Bromophenylacetic acid amides (4a,b) were prepared from 2-bromo-2-phenylacetyl chloride [38] and the corresponding amine in DCM or toluene at reduced temperature (see Supporting Information File 1). Thiobenzamides and thiobenzanilides were prepared by magnesium chloride-catalyzed thiolysis of

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• abstraction (HAT) followed by single electron transfer (SET) enabled by the sulfate radical anion (SO4·−). Results and Discussion Initially, we investigated the reaction of N-benzenesulfonyl(benzyl)amine (1a) as a model substrate with K2S2O8 in MeCN at 80 °C for 12 h, conditions that were used earlier in our

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• carbonyl component was proposed, but these aldehydes did not have the structure of imidazo[1,2-a]pyridine. Interestingly, in 2019 [1], the synthesis of the amine component using GBB-3CR and the modification of the imidazo-pyrimidine scaffold by a peptidomimetic chain was carried out using the Ugi reaction

• . Without isolation, the corresponding aldehyde, amine and isocyanide were added to the resulting iminopyridine product and the mixture was then stirred at room temperature for 12 h. But again, the expected compounds could not be obtained. Following this trend and based on published data, we synthesized

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• imine species provide a very flexible approach to the arylglycine scaffold [2][9]. The Petasis borono-Mannich reaction constitutes a prominent example for such an imine-based multicomponent reaction (Scheme 1a). The reaction of glyoxylic acid, an amine component and an arylboronic acid offers a highly

• electrophilic iminium carbon, leading to the amine product as racemic mixture. Consequently, examples for asymmetric Petasis borono-Mannich reactions are rare [13] and usually rely on the utilization of chiral amine components in stoichiometric amounts [10][11]. As part of our research program utilizing the in

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

• of o-nitrotoluene (22) Reduction to 2,2'-diaminobibenzyl (20) Ring-closing via amine condensation Catalytic dehydrogenation 1.1 Oxidative coupling of o-nitrotoluene (22) and reduction to 2,2'-diaminobibenzyl (20) The preparation of dinitrobibenzyl (21) can be achieved by the oxidative coupling of

• transition metal (Ni, Fe, V) porphyrin catalysts and oxygen. Catalytic reduction (H2, Pd/C) affords 2,2'-diaminobibenzyl (20) in the subsequent step [28]. 1.2 Ring-closing via amine condensation The initial synthesis of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a) was reported in 1899 by Thiele and Holzinger

• '-dibromostilbenes 61 by means of a double Buchwald–Hartwig amination gave yields between 62% and 96% using aniline as the amine reactant (Scheme 13). The reaction proved to be compatible with both aromatic and aliphatic amines and the reaction time varied between 11 and 24 hours. Fluoro, chloro, nitrile, alkyl, and

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

• due to the solubility of the starting amine 11d and the corresponding products 12. In addition, in the reaction of APBTT 1a with mesidine (11b), we succeeded to isolate a side-product 14ab (Scheme 19). Similar side-products 14 were observed in all reactions of APBTTs 1 with arylamines 11 (UPLC–UV–MS

• nucleophilicity of the amine. Then, we examined the proposed approach to PBTAs by involving bulky nucleophilic compounds 16a–d to the reaction with APBTT 1a. Unexpectedly, product 17a was formed instead of the anticipated PBTA C (Scheme 20). Compound 17a was formed in good isolated yields (60–70%) and was

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

• secondary amine 157 generated in the cyclization step (Scheme 40B). Consequently, the complex tetracyclic compound 158 was produced in 47% yield and with good stereoselectivity (84% ee, dr 7.5:1). At about the same time, comparable results were reported by the group of Zhang [82]. Their Cu-catalyzed cascade

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

• -situ imine formation is currently impossible with catalytic or stoichiometric amounts of amine due to decarbonylation of furfural under the reaction conditions [21]. We thus present here an adaptation of our Ru(0)-catalyzed C3-alkylation strategy of furfural derivatives to a continuous flow system

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

• (5). This compound was synthesized smoothly within three steps in 16.6% overall yield. The synthetic route commenced from the preparation of N-protected amine 3, followed by the deprotection of benzylamine 3 to furnish 4 and ended with the diazotization of 4 using tert-butyl nitrite. As a result, the

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

• lab reported the Rh-catalyzed domino reaction of doubly bridgehead-substituted oxabicyclic alkenes 134 with secondary amine nucleophiles 135 for the synthesis of bicyclo[2.2.2]lactones 136 (Scheme 24) [70]. This reaction proceeded smoothly with a variety of secondary amine nucleophiles, including

• undergo the domino reaction, generating the desired bicyclo[2.2.2]lactone 136. The authors proposed the reaction first takes place through an ARO of the doubly bridgehead-substituted oxabicyclic alkene with the secondary amine nucleophile ultimately producing 137. The Rh(I) catalyst then facilitates the

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• -linked porphyrin-fullerene dyads 100a–d and 104a,b. Firstly, meso-triazole-linked porphyrin conjugates 99a–d and 103a,b were synthesized from porphyrins 97a,b and 101, as shown in Scheme 20. For the click reaction between porphyrin 101 and alkyne 102a,b, one equivalent of tris(benzotriazolylmethyl)amine

• (TBTA) was also added as an additive to increase the yield of triazoloporphyrins 103a,b. When TBTA, a tertiary amine with a 1,2,3-triazole ring, is added to a Cu-catalyzed click reaction, it forms a complex to stabilize the Cu(I) oxidation state and speeds up the reaction. Further, these 1,2,3-triazole

• 124 in the presence of copper bromide and tris((1-benzyl-4-triazolyl)methyl)amine (TBTA) in DMSO/H2O to give a porphyrin-lantern (PL)-DNA sequence in 45% yield after cleavage and deprotection. These PL-DNA sequences were further used to construct strong and fluorescent G-wires that could be useful for

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• borylation of thiols with HBpin (Scheme 17) [79]. Through computational analysis, a mechanism was proposed whereby the ambiphilic amine-borane 73 underwent concerted addition to the thiol 74 S–H bond, to give a zwitterion 75. After loss of H2, a neutral thioborane 76 was generated, which underwent B‒S/B‒H

• transborylation with HBpin, to give the thioBpin 77 product and regenerate the amine-borane catalyst 73 (Scheme 17). Yamamoto reported the borane-catalysed hydroalumination of alkenes and allenes (Scheme 18) [80][81][82][83] in which the organoaluminium products were reacted in situ with various electrophiles to

• dihydride-catalysed the dehydrocoupling of HBpin or H-B-9-BBN with primary and secondary amines (Scheme 22) [84]. The reaction was proposed to proceed by double dehydrocoupling of the amine 87 and aluminium dihydride 88 to give a bisamido aluminium species 89 which underwent Al‒N/B‒H exchange with HBpin to

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

• readily reduced to mono(6-amino-6-deoxy)-CDs (NH2-CDs) opening the way for the preparation of amine, thioureido or amide-linked CD scaffolds [14]. Several other nucleophiles can react with mono-6-O-tosyl-CDs, such as iodide, dithiol, hydroxylamine, alkylamine or polyalkylamine to give iodo- [15], thio

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

• endocyclic nitrogen with a benzyl or alkyl unit functionalized either with non-polar hydrocarbons or a polar amine, amidine and guanidine group. The ensuing assay with the model GMIIb enzyme (fruit fly Golgi α-mannosidase II) revealed that N-substitution improved both potency and selectivity, achieving

• the acetonide and subsequent alkylation of the liberated amine with the corresponding arylalkyl bromides under basic conditions provided the desired N-arylalkyl iminosugars 8 and 9 in moderate yields. In addition, acidic hydrolysis of the acetonide group in 6 afforded the target derivative 7 which

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• potassium hydroxide tend to terminate at the 2-position. This results in the formation of POx containing a secondary amine and a cleavable ester terminal group [49]. Subsequent dehydration under conditions of MALDI-TOF mass spectrometry might lead to a dehydration, although this is speculative at this point

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• formation of the cis-vinylcyclopropanes (Scheme 18c and 18d). Desulfurization of the adducts again yields the product of a formal cyclopropanation with a ‘naked’ vinyl carbene species, as demonstrated by the stereoselective synthesis of the protected cis-2-vinylcyclopropan-1-amine 123 (Scheme 18d). 7

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• °C and with the use of 1.3 equivalents of AgOTf. Finally, we sought to check the reactivity of other substituents on the amine component of acyclic imine substrates. With the use of benzyl-substituted aldimine, the aza-Nazarov product 19l was obtained in 49% yield and with 10:1 dr. Similarly, the aza

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

• chiral aldehyde 127 and Boc-protected amine 128, followed by zinc reduction of the nitro group and subsequent protection of the amine by a tosyl group in 27% overall yield. Irradiating 129 with blue light at 30 W in the presence of 1 mol % of [Ir(dtbbpy)(ppy)2]PF6 and 5 equiv of KHCO3 in THF resulted in

• ). Thus, upon irradiation, iridium polypyridyl photocatalyst allowed the oxidation of the phosphate complex 207 to radical cation 206, which can be readily trapped by TEMPO, and hence stabilizing the imine and allowing cyclization with the pendant amine to form the pyrroloindoline core 210 in 81% yield

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• analysis to control the acid concentration. Good extraction efficiency and purification were achieved for an amine as a test substrate that was contaminated with a minor impurity. Remaining challenges such as time-consuming optimization and the need for several pumps can be overcome through careful

• of the ethyl acetate solvent (used as acetyl donor) whereas the recovered aqueous phase contains the unreacted amine that can be recirculated in the system (Scheme 3) [54]. Amongst the commonly cited challenges of implementing these membranes are their high cost and the perceived difficulties

• impurity might also contain the same functional group that has affinity to the resin (Scheme 10). QP-SA is a commonly used resin which contains –SO3H groups and can sequester amines, whereby a solution of ammonia in MeOH can be used to release the product [94]. Amine-functionalized resins like A-900 can be

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• classified according to the catalytically active species or key intermediates: N-oxyl radicals, oxoammonium cations, amine cation radicals, thiyl radicals, quinones, dioxiranes and oxaziridines, hypervalent iodine compounds, etc. However, some examples of organocatalyzed oxidative processes, in which an

• play an important role in redox-neutral asymmetric organocatalysis by forming nucleophilic enamine intermediates or electrophilic iminium cations. The same principles are used in oxidative transformations, where an amine can play the role of chirality source and the activator of substrate for oxidation

• improved stability and tunable reactivity by structure modification. Amine-N-oxyl radical/oxoammonium cation catalysis Compared to the N-oxyl radical catalysis discussed above, where reactive N-oxyl radicals represent an active organocatalyst form generated in situ, in oxoammonium cation catalysis [74][76

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• ] which underwent aromatization with the loss of sulfur dioxide and N-Boc-aniline. The multicomponent character and the fairly large scope of this reaction allows to place pairwise reactive groups in the aldehyde and the amine components, which would set a scene for further elaboration of the product’s

• ) [6]. Indeed, if an alkyne and an azido group were strategically positioned within the structure of the amine and the aldehyde components for the reaction with 1, subsequent intramolecular azide–alkyne cycloaddition would be a feasible event which would create a polycyclic bis-1,2,3-triazole framework

• (Figure 1). Herein, we report on a successful realization of this strategy. Results and Discussion To test the possibility of a tandem double cycloaddition reaction between 1, an alkyne-containing amine and an azide-containing aldehyde, we set up a reaction of 1 with o-azidobenzaldehyde (3a) and

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• amine derivatives (e.g., hydrochloride salt, mandelic acid salt, phthalimide, ketopinic acid amide, salicylaldehyde imine, p-toluenesulfonamide, acetamide, etc.), all attempts to separate the resulting isomers (which were oils) were similarly unsuccessful. Seeking an alternative to column chromatography

• anticipated that the amide 5 could be hydrolyzed to give a single enantiomer of amine 4. However, we found that amide 5 was remarkably resistant to hydrolysis, even under forcing conditions. For example, no amide hydrolysis was observed in concentrated aqueous NaOH solution at reflux (with or without an

• using hydride reducing agents [13]. Nevertheless, specialized conditions for achieving C–N-bond cleavage of amides using SmI2 [13], Tf2O/Et3SiH [14], and stoichiometric Schwartz’s reagent [15] have been reported; however, none of these methods was successful in reducing amide 5 to the desired amine 4

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• . Subsequent reduction with sodium dithionite then afforded triamine 9. Another way comprised the installation of a nitroso group in compound 6 through reaction with in situ-generated nitrous acid giving nitroso compound 8. The subsequent reduction to the corresponding amine with hydrogen sulfide afforded the

• 3,4-dihydropyran in dimethylformamide to obtain the corresponding tetrahydropyranyl-protected amine 17. Subsequently, a copper-catalyzed C–O bond formation at C6 using benzyl alcohol in the presence of caesium carbonate, copper(I) iodide, and 1,10-phenanthroline furnished benzyl ether 18 in excellent

• yields [22]. The switch from 2-tetrahydropyranyl to tert-butyloxycarbonyl protected compound 19 was required for an efficient installation of the exocyclic amine via regioselective nitration in the presence of trifluoroacetic anhydride (TFAA) and tetrabutylammonium nitrate (TBAN) to give a mixture of the