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

• involves the formation of (dibenzylamido)yttrium complex 28 by the reaction of yttrium complex 26 with HNBn2. Then σ-bond metathesis between the Y–N bond of 28 and the ortho-C–H bond of pyridine gives η2-pyridyl species 29 which on imine insertion produces species 30. Subsequent protonation then provides

• yields generating a library of isonicotinic and nicotinic acid derivatives. Another inexpensive and non-toxic iron-catalyzed C–H arylation of pyridines has been reported by DeBeof and co-workers [98]. Using the imine in 147 as directing group, afforded the arylated pyridine products 150 in good to high

• reaction conditions. Also, the additive KF was employed in order to minimize the oxidative iron-catalyzed homocoupling of 148. An imine directing group at the para-position in pyridine 147 lead to activated ortho-position products 150 within 15 minutes. The imine group of the products can further be

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

• . recommended [24] a polar aprotic solvent such as DMSO that facilitates the formation of both α-thioiminium salt (III) as well as Eschenmoser contraction involving the attack of the exposed carbanion towards the imine/iminium group (V). Based on our previous experience [3][4] we favor dimethylformamide (DMF

• ) level of theory. Quantum calculations (Figure 2) have shown that the reaction pathway that involves an intramolecular proton transfer between the α-carbon and imine nitrogen through TS1 is much more favorable for imidothioate derived from 4-bromoisoquinoline-1,3(2H,4H)-dione (3) and 3-bromooxindole (1

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

• single electron transfer (SET), is proposed to be involved in the plausible reaction mechanism. Keywords: arylsulfonylimine; benzylic oxidation; benzyl sulfonamide; K2S2O8; sulfate radical anion; Introduction Among various imine compounds [1], N-arylsulfonylimines are perhaps the most prominent due to

• of the intermediate product 2c and 2-aminobenzamide gave 2-(p-tolyl)quinazolin-4(3H)-one (4b) in 85% yield. Furthermore, when various other ortho-substituted aniline derivatives such as 2-aminobenzylamine, 2-aminothiophenol, and o-phenylenediamine are reacted with imine 2a in a similar manner, the

• abstracts the activated NH proton to produce imine 2. The dual role of SO4·− involving HAT and SET is proposed in this plausible mechanism, which requires further investigation. Similarly, a plausible mechanism for the one-pot synthesis of N-heterocycles is shown in Scheme 6. Initially, the N

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• through oxidative cyclodehydrogenation and imine formation in a 72% yield. It was noted that no other regioisomer was detected for the asymmetrical precursor 30. The pair of enantiomers was confirmed by the racemic structure's single-crystal X-ray diffractometry and separated by chiral HPLC, and no

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

• situ generation of reactive imine species, we have disclosed iron- and bismuth-catalyzed three-component reactions for the synthesis of α-arylglycines [14][15][16], in which the arylboronic acid could be replaced with an electron-rich (hetero)arene as nucleophile. In parallel, we have developed

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

• been shown to impart high levels of enantioselectivity for these ketones [46]. We performed the conjugate addition for 2 h and then added imine 58 having a tosyl protecting group. The workup allowed the isolation of domino products 59 as a mixture of diastereomers with dr 3:2 and enantiomeric purities

• introduced during the conjugate addition). On the other hand, a typical problem of these reactions was also revealed. The diastereoselectivity with respect to the addition to the imine was only very modest. To address the problem of low facial selectivity of the imine addition, we continued our study with

• ligands is that they can also promote the conjugate additions of aryl-based or branched Grignard reagents (Scheme 17) [49]. Further extending this methodology, we have investigated formaldehyde imine equivalents. These kinds of imines are not readily available, but they are highly important synthetic

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

• .19.43 Abstract The C3-functionalization of furfural using homogeneous ruthenium catalysts requires the preinstallation of an ortho-directing imine group, as well as high temperatures, which did not allow scaling up, at least under batch conditions. In order to design a safer process, we set out to

• formation of the imine directing group and the C3-functionalization with some vinylsilanes and norbonene. Keywords: biomass; C–H activation; flow; furfural; homogeneous catalysis; Introduction The conversion of biomass derivatives into value-added products is one of the key branches of green chemistry and

• reaction conditions while providing products in shorter reaction times. In addition, the ability to couple multiple reactors with a flow apparatus could also enable us to perform these functionalizations directly from furfural by forming the imine in a first reactor. It should be noted that, in batch, in

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• reversibility can be reached at scan rates above 20 V/s allowing the E1/2 estimation. Similarly to previously studied complex (ΔAlaNi)L1 [36], electron transfer to (ΔAlaNi)L7 is mainly ligand centered. The DFT-estimated LUMO is formed as an overlap of the π antibonding orbitals of the dehydroalanine and imine

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

• occurs producing 144. Subsequently, coordination of the Rh(I) to the electrophilic cyano group leads to an intramolecular addition producing 145. The imine undergoes a hydrolysis releasing the final carboannulated product 141 as well as regeneration of the active Rh(I) catalyst. A similar mechanism can

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• )) geometries for the transition structures of series a–f. Top: Cycloaddition of protonated hydrazones as inverse-demand reaction of cycloaddition of azomethine imines. Bottom: molecular orbitals involved in the reaction and energy diagram of the reactivity of ethylene with azomethine imine and protonated

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• nucleophilic attack of morpholine (C) on elemental sulfur may react with the intermediate 13 to afford another intermediate 15, which undergoes oxidation to release the thioamide-tethered pyrazole 1C. On the other hand, the pyrazole carbaldehyde 1 forms imine intermediate 16 by condensation with 2

• -aminopyridine. Thereafter, a nucleophilic attack of H2O2 on the imine carbon may afford the intermediate 17. Finally, the loss of a water molecule from the intermediate 17 may generate the pyrazole-pyridine conjugate with amide linkage 1F. Conclusion In summary, a simple, straightforward and efficient approach

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• , which undergoes a rapid migratory insertion to give intermediate 1-C. The protonation of 1-C produces the intermediate 1-D with the regeneration of the active Rh catalyst for the next catalytic cycle. Under acidic conditions, the further protonation of compound 1-D delivers an imine intermediate 1-E

• , which undergoes an intramolecular annulation to give 1-F. The final isocoumarin product 3ba can be generated from 1-F by elimination of imine 1-G [39]. Finally, the rapid hydrolysis of the resulting 1-G gives rise to acetaldehyde and dimethylamine as byproducts. Conclusion In summary, an efficient Rh

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

• , entry 4). The scope of the reaction with 3,4-dihydroisoquinoline substrates as cyclic imines was investigated under these conditions [35]. In the current work, we first opted to examine the activities of other Lewis acids in the aza-Nazarov cyclization of imine 5a with acyl chloride 6b. The reason of

• , were obtained as single diastereomers. In order to assess the scalability of the aza-Nazarov cyclization, we investigated the synthesis of the previously unreported lactam 7c via the reaction between imine 5b and acyl chloride 6b on a gram scale (Scheme 2). Acyl chloride 6b was prepared in four steps

• chloride at 60 °C in 95% yield (2.6 g) and with a dr (E:Z) of 3:1 (Scheme 2a). When imine 5b was reacted with 6b on an 8.0 mmol scale with the use of AgOTf (20 mol %) in acetonitrile at 80 °C, the aza-Nazarov product 7c was isolated in 61% yield (1.42 g) as a single diastereomer. This result clearly

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

• in the formation of spirolactam 157 in 73% yield (Scheme 13). The reaction is estimated to take place initially with the one electron reduction to α-amino radical 164. This step is thought to be facilitated after TFA protonates the formed imine. Afterwards, radical addition of 164 to 156, generates

• ). 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

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

• intermediate is depicted in Scheme 28). Quinone derivatives could also be generated in situ by anodic oxidation of phenolic compounds. An example of such process is the electrocatalytic biomimetic synthesis of secondary amines by o-azaquinone catalysis [130] (Scheme 29). Under anodic oxidation conditions imine

• of a hydroperoxide (terminal oxidant) on a ketone or imine, respectively, is followed by intramolecular cyclization with O–O bond cleavage and the formation of a strained 3-membered ring, an electrophilic oxygen atom donor for oxidative processes (Scheme 30). It should be noted that in the ketone

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

• derived from a common biosynthetic pathway starting from farnesyl pyrophosphate and glycine [5]. This prompted us to investigate a biomimetic synthesis in which the halichonic acids could be prepared from a common imine intermediate via divergent intramolecular aza-Prins cyclizations [8]. Herein, we

• 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

• evolution (likely H2) occurred. However, no reduction of the amide was observed, even after stirring at room temperature for 24 hours. In an effort to “salvage” the reaction by reducing the amide to the corresponding N-benzylamine (which could potentially be oxidized to the corresponding imine with IBX [18

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• bearing a free amino group (Scheme 4). However, this product was prone to a ring–chain isomerization forming an equilibrating mixture of azaadamantane 15, tris-imine 16, and bicycle 17 in solution as determined by NMR data (see Supporting Information File 1 for details). We were able to shift the

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• and preparation of suitable salen compounds, sometimes are described as bis-imine Schiff bases. Imines were originally synthesized by Schiff from the condensation of carbonyls with amines [25]. Thereafter, syntheses of salens were extensively reported using timely technologies [26][27][28][29

• ethylenediamine monohydrochlorides were grinded with a half equivalent of 4-diethylamino (Et2N‒), 3,5-dichloro (Cl‒), or 3,5-di-tert-butyl (t-Bu‒) salicylaldehydes (blue moieties in Scheme 2) for 10 minutes. The synthesis of diamine monohydrochlorides and characterization data of mono-imine ammonium salts were

• described before [30][31][32][33][36]. This process generates mono-imine ammonium salts as the stable intermediates in the mortar. Without implementing treatment such as filtration, evaporation of solvents, or further purification, mono-imine ammonium salts were subsequently treated with triethylamine (Et3N

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• active site thiohemiaminal (amine to imine oxidation) or disulfide formation, respectively. Additionally, C6–Cl derivative 9 could probe cysteine alkylation. Reported herein is our exploration of this synthesis and the evaluation of GDP 6-chloro-6-deoxy-ᴅ-mannose 18 against GMD. Results and Discussion

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• ), Dunkerque, France 10.3762/bjoc.18.140 Abstract A simple method for the preparation of β-cyclodextrin derivatives containing covalently bonded aldehydes via an imine bond was developed and used to prepare a series of derivatives from 6I-amino-6I-deoxy-β-cyclodextrin and the following volatile aldehydes

• benzaldehyde) and static headspace-gas chromatography (for benzaldehyde, heptanal, and 5-methylfurfural). The aldehyde release rate from the imine was shown to depend substantially on the pH from the solution and the air humidity from the solid state. Keywords: aldehyde; controlled release; cyclodextrin

• ; imine; kinetics; pro-fragrance; Schiff base; Introduction The fragrance and flavor industry is one of the most intensively developing sectors of the chemical industry. Encapsulation techniques are widely used in both food and cosmetic industries to control the delivery of the encapsulated guest

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• species 2. This can undergo B–N/B–H transborylation with HBpin to give the N-Bpin imine 3, followed by a second hydroboration and B–N/B–H transborylation to give the N,N-bis-Bpin amine product 4. Alternatively, the imido-boryl intermediate 2 undergoes a second hydroboration to form the N,N-bis-borylamine

• comparable activity to H3B·SMe2 (Scheme 3b) and the reduced number of reactive B–H sites to reduce complexity. Following hydroboration of the nitrile by H-B-9-BBN to give the N-B-9-BBN imine 6, the reaction can proceed by two routes to give the N,N-bis-Bpin amine 4a: A) a second hydroboration by H-B-9-BBN to

• give N,N-bis-B-9-BBN amine 7 and two B–N/B–H transborylation reactions with HBpin; B) B–N/B–H transborylation with HBpin to give N-Bpin imine 8 and a further hydroboration by H-B-9-BBN and B–N/B–H transborylation (Scheme 3c). Route A was found to have a highest energy barrier of 25.5 kcal mol−1 for the

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• of L. Overman et al. in 1997 [18] towards the originally proposed structure of palau’amine (44), a [3 + 2]-dipolar cycloaddition of α-ketoester 41 and the thiosemicarbazide 42-derived azomethine imine VI to the triazacyclopenta[cd]pentalene 43 was utilized as a key step (Scheme 7) [18][19][20][21

• in the synthesis of (+)-gracilamine (83), a pentacyclic alkaloid isolated from the plant Galanthus gracilis, (Scheme 13) [28]. The synthesis started from readily available sesamol (79) and imine 78 which gave the advanced intermediate 80 in ten steps. An intramolecular Mannich reaction of compound 80

• of an α-ketoester through Riley oxidation and its use in an α-ketol rearrangement in the synthesis of (−)-jiadifenoxolane A (36) [15]. Azomethine imine cycloaddition towards the synthesis of the proposed structure of palau’amine (44) [19]. Intramolecular diastereoselective carbonyl-ene reaction of an

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• )) revealed that the stability of the two isomers was very similar, with a difference in ΔG of only 2.6 kJ⋅mol−1 and 2H-benzo-1,4-thiazine 11b being more stable (Figure 2). It seems likely that initially enamine dimer 11a formed, which then tautomerized to the more stable imine form 11b. As a continuation of

• benzothiazine dimers were isolated. Typical benzothiazine structures. DFT (ωB97xD/6-31G*)-calculated structures of enamine and imine tautomers 11a and 11b. Condensation reactions of 2-aminothiophenols 8 and bromopyruvic acid and esters 9. Direct synthesis of dimer 11a under oxidative reaction conditions

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• , alanine, serine and cysteine derivatives are formed as an antibonding combination of the Ni dx²-y² orbital with the group orbitals of the ligands; the π* orbital of the imine and the π orbital of the phenylene fragments are also partially involved. Reduction occurs at similar potential values and is

• the nucleophilic attack at the imine fragment yielding new complex 5 (Scheme 3), which was isolated in the form of two diastereomers in a total yield of 37%, indicating that this reaction route dominates. The compounds were characterized with NMR (2D technique, see Supporting Information File 1

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• -ones 4a–c occurs via the acid-catalyzed condensation of the aromatic aldehyde 1a–c and aniline (2) to produce imine intermediate 5 which is then protonated to the iminium species 6. In addition, ethyl 2,4-dioxovalerate (3) containing an activated methylene group is in fast equilibrium with enol