N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• for the aziridine ring opening and the removal of the 1-phenylethyl group and also for the reduction of the intermediate cyclic imine which appeared stereospecific. Two other piperidine alkaloids, (+)-deoxocassine ((2S,3S,6R)-190a) and (+)-spectaline ((2S,3S,6R)-190b) were synthesized as hydrochloride

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• addition with a subsequent intramolecular cyclization catalyzed by Cu(BDC)MOF. Further, the LC–MS study of the reaction mixture has shown the imine formation to be the major pathway rather than β-nitrostyrene. The reaction involved a two-step reaction mechanism in which aza-Michael adduct 13 was formed in

• the formation of radical intermediates, as use of TEMPO inhibited intramolecular C(sp3)–H amination of imine species. Aerial oxidation of the Cu(I) species bonded to the N-atom of pyridine and imine 39 resulted in Cu(II) superoxo radical intermediate 40. This was followed by intramolecular hydrogen

• sodium ascorbate (NaOAs) helped in the reduction of Cu(II) to Cu(I) which then reacted with the alkyne moiety. The species thus formed participated in the reaction by reacting with imine of aldehyde and amidine. The intermediate thus formed undergo 5-exo-dig cyclization and 1,3-H shift to form the final

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• nucleophilic substitution of chlorine in the chloroethynylphosphonate to form ynamine intermediate A, isomerization of which provides ketenimine B. Further formation of the imine tautomer C enables an intramolecular 5-exo-dig cyclization to furnish the title [1,2,4]triazolo[4,3-a]pyridines (Scheme 6

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• ylide, or by condensation of a primary amine with an aldehyde to give an imine followed by prototropy or deprotonation to give N-metalated azomethine ylides (see, for example, [5][6][7][8][9][10][11][12][13][14][15][16][17][18]). An alternative method is to prepare a salt of a heterocycle, typically by

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• materials for relevant MCRs such as those based on imine and isocyanide. The focus is mainly posed on proving the amenability of MCRs for the diversity-oriented derivatization of naturally occurring steroids and the construction of complex steroid-based platforms for drug discovery, chemical biology and

• first step of the Ugi-4CR reaction, i.e., the formation of the imine between the ketosteroid and the amine group of the aminopyridine derivative. Then, the imine suffers the nucleophilic attack of the isocyanide generating a nitrilium intermediate. Differently from the Ugi-4CR, the final step is the

• cyclization between the pyridine N atom and the isocyanide. TP3 plays the catalytic role by acidic activation of the ketone to favor the imine formation. 2.1.2 Steroids as amine and carboxylic acid components: Several groups have employed steroidal substrates as amino and carboxylic acid components of the Ugi

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• through an addition of copper acetylide, generated from terminal alkyne and copper, to the imine formed by the reaction between the amine and the formyl group. Then, the secondary propargylamine intermediate would act as a nucleophile in a cyclization process to form the lactam ring. The same

• became predominant. Similarly to the above mentioned method, the first step in this approach is probably the imine formation by reaction of amine 2 with the aldehyde functionality of benzoate 29. Next, addition of the enol form of ketone 31 onto the imine would provide a Mannich intermediate amine, which

• start with the formation of an imine intermediate between the aldehyde function of 33 and the amine 2, followed by a nucleophilic attack by the diketone and a final intramolecular cyclization, the Han group proposes a different pathway, with an initial deprotonation of ketoacid 34 (R2 = Me, Ar, R3 = OH

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride

• Aytekin Köse,
• Aslı Ünal,
• Ertan Şahin,
• Uğur Bozkaya and
• Yunus Kara

Beilstein J. Org. Chem. 2019, 15, 931–936, doi:10.3762/bjoc.15.89

• Schwarz [15]. In our continuing studies on the synthesis of isoindole derivatives, we have included the addition of CSI to unsaturated systems and obtained unexpected results. When the reactions were performed by heating without any solvent, the condensation product imine was the sole product. In this

• ] contribute to the formation of a stable structure (Figure 2a and Figure 2b). Based on the structure of the product, we propose the reaction mechanism shown in Scheme 4. First, CSI reacts with the carbonyl carbon in the imide ring to form a four-membered urethane ring. Afterwards the imine is formed by the

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• isocyanide 57 and acetic acid, followed by reaction of the resulting formamide with triphosgene (Scheme 12). Compound 58 was obtained as a 78:22 diastereomeric ratio without any racemization of the pre-existing stereocenter and then used in the key step Ugi-type 3CR with cyclic imine 59 (generated in situ

• has been found in the use of dynamic combinatorial chemistry (DCC) [42]. One of the most accessible reversible bonds is the imine bond and has been widely used in DCC. In this context, a freezing process of a dynamic combinatorial library (DCL), which is a system of recognition and thermodynamic

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• milling frequency of 22.5 Hz (Figure 6b) [59]. The stoppers were constructed in situ with 1,8-diaminonaphthalene through the formation of an imine via dehydration of the amine and aldehyde. Interestingly, a synthesis of the smallest [2]rotaxane also has been demonstrated by the same group [60]. They

• stabilities by exhibiting a decomposition temperature up to 320 °C. In 2013, Severin and co-workers reported the mechanochemical synthesis of large macrocycles with borasiloxane and imine links using a ball mill (Figure 12). In a polycondensation reaction using diamines, 4-formylbenzeneboronic acid and t

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• component that leads to the formation of an imine intermediate A. The formed Schiff base is in equilibrium with its iminium cation B as a result of an intramolecular proton exchange with the carboxylic acid moiety which activates the iminium ion for the nucleophilic addition of isocyanide. Consequently, the

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• gave the best results (method A) and in a few examples ammonium bicarbonate was tested as alternative (method B) [29][33]. The plausible mechanism of this transformation involves the formation of an α,β-unsaturated imine G and its cyclization to H followed by water elimination. As characteristic

• reaction of pivalonitrile (1) with lithiated methoxyallene 2 leads to allenyl-substituted imine 3 which upon reaction with trifluoroacetic acid affords β-ketoenamide 5 and pyridin-4-ol derivative 6. Proposed mechanism of the LANCA three-component reaction to β-ketoenamides KE and pyridin-4-ol derivatives

Design, synthesis and spectroscopic properties of crown ether-capped dibenzotetraaza[14]annulenes

• Krzysztof M. Zwoliński and
• Julita Eilmes

Beilstein J. Org. Chem. 2019, 15, 617–622, doi:10.3762/bjoc.15.57

• bands at ca. 1590 and 1560 cm−1, assignable to the olefinic and imine skeletal stretching modes, implies the macrocyclic scaffold integrity. The FTIR-ATR spectra consist also with the characteristic, but modest in intensity, the absorption band at ca. 1646 cm−1 attributable to the carbonyl moiety

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• polymerizations; E) alkyne-sulfonylazide-alcohol interactions; F) sulfur-amine-isocyanide combination. Concept of multicomponent macrocyclization. Supramolecular structures out of MMCR macrocyclizations. Macrocyclization by MMCRs. A) Staudinger MCR; B) boronic-imine MCR. Selective Sequential MMCRs. A and B) MCRs

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• , after hydrazinolysis with N2H4.H2O in slight excess. The crude product was reacted with formaldehyde in boiling MeOH, and after 1 h, crystalline N-(adamantyloxy)formaldimine (6a) was isolated in 90% yield. The spectroscopic data indicate that this imine exists in solution in monomeric form exclusively

• . Thus, the 1H NMR spectra confirmed this structure by the presence of two doublets located at 6.39 and 7.01 ppm with J = 12 Hz, characteristic for the =CH2 group. In addition, the 13C NMR spectrum showed the absorption of this group at 136.1 ppm. Having imine 6a in hands, syntheses of a series of 2

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• acids take advantage of the intermediary formation of the pyrrolidine ring. Addition of the dianion of 43 to acrolein gave a 69:31 mixture of diastereoisomers with compound 44 predominating which was easily separated on silica gel. When imine 45 was treated with iodine a stereoselective

• groups were removed by concentrated acid. A very efficient synthesis of (2S,3S,4S)-4 starts from another serine-derived chiron, namely O-benzyl-N-Boc-D-serine [111], which was readily transformed to the Z-olefin 120 containing a benzophenone imine residue as a nitrogen protecting group (Scheme 29

• of (+)-polyoxamic acid (Scheme 30) [113]. To this end the anion generated from benzophenone imine of tert-butyl glycinate 124 acted as a Michael donor in the presence of homochiral catalyst to give a ca. 1:1 mixture of diastereoisomeric iminoselenides 125 with an ee up to 96% (Scheme 30). Next, a 9

Reactions of 3-(p-substituted-phenyl)-5-chloromethyl-1,2,4-oxadiazoles with KCN leading to acetonitriles and alkanes via a non-reductive decyanation pathway

• Akın Sağırlı and
• Yaşar Dürüst

Beilstein J. Org. Chem. 2018, 14, 3011–3017, doi:10.3762/bjoc.14.280

• − anions, cyanoimine salt intermediate A forms by addition to a nitrile. Then, a possible cyanogen release would occur to form intermediate B. The imine–enamine tautomerization of B by the effect of in situ-generated HCN results in the desired decyanated product 4 (Scheme 2). Conclusion In summary, we

1,8-Bis(dimethylamino)naphthyl-2-ketimines: Inside vs outside protonation

• A. S. Antonov,
• A. F. Pozharskii,
• P. M. Tolstoy,
• A. Filarowski and
• O. V. Khoroshilova

Beilstein J. Org. Chem. 2018, 14, 2940–2948, doi:10.3762/bjoc.14.273

• rotation of the NH2+ fragment in dications. Keywords: hydrogen bond; imine; NMR; proton sponge; superbase; Introduction It is well known that the extremely high basicity of 1,8-bis(dimethylamino)naphthalene (1, DMAN; pKa = 12.1 in H2O [1][2], 18.62 in MeCN [3], 7.5 in DMSO [4]) and its derivatives

• only be imine nitrogen, i.e., the structure corresponds to monocations 4b’–7b’ (Scheme 7). Indeed, around 10 ppm, a new signal appears which corresponds to two NH protons. To our knowledge, this is the first example of an imine to be basic enough to successfully compete for a proton with the proton

• sponge moiety: for example, the basicity of benzophenone imine (pKa = 6.82) and even that of cyclohexanone imine (pKa = 9.15) [12] is much lower than that of DMAN (pKa = 12.1) [1][2]. Moreover, as it was already mentioned in the introduction, this is the third known example of a DMAN derivative with a

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• . Analyzing the mechanism of the reaction between the 2-formylbenzoic acid 4 and α-amino acid arylhydrazides 3, we assumed that the first steps lead to the formation of the imine intermediate A, which is the result of the nucleophile addition of the α-amino group on the most electrophilic center in 4. This

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• useful synthons [72][73] in the presence of open atmosphere (Scheme 1b). Results and Discussion We have commenced the model reaction between cyclic N-sulfonyl imine 1a as interesting C,N-binucleophiles [74] and MBH carbonate of acrylate 2a using 20 mol % of DABCO in toluene at room temperature for 14 h

Carbonylonium ions: the onium ions of the carbonyl group

• Daniel Blanco-Ania and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2018, 14, 2568–2571, doi:10.3762/bjoc.14.233

• followed by a suffix indicating the positively-charged groups has made nomenclature richer and more fluent. IUPAC has given name to several functional groups as protonated species and organyl derivatives thereof: imine–iminium, amide–amidium, nitrile–nitrilium, amine–aminium [34]. In this sense, we propose

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• cathodic reactivity of the monoalkylated complex of 1 was found to be critical to the selectivity of the migrating group. Interestingly, the electrochemical carbon-skeleton rearrangement reactions were successfully mediated by simple B12 model complexes 2 (Figure 3). The imine/oxime-type square planar

• ligands of cobalt complexes 2 are superior to porphyrin ligands in terms of the model for the corrin framework of B12; both the imine/oxime-type and corrin ligands are monoanionic [57][58][59][60]. The imine/oxime-type cobalt complex 2 can be isolated in both the monoalkylated and dialkylated forms [59

• was vital for the activation of 1-octanethiol [76]. A similar reaction was successfully mediated by the imine/oxime-type cobalt complex 2a using zinc powder [77]. 3-2. Methyl transfer to inorganic arsenic for the detoxification of arsenic The wide utilization of inorganic arsenics causes large-scale

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• reagent. Then, imine 9 assisted an ortho C–H metallation by oxidative addition and provides Co–H intermediate D1. Coordination of alkene with D1 and insertion of the alkene to Co–H gives intermediate D3 or D3’, which is converted into product 27 or 28 and low-valent cobalt by reductive elimination

• hydroarylation of glyoxylate with pyrimidine containing indoles and pyrroles 7 to provide products 63 with high productivity (Scheme 40) [79]. Similar to the imine, isocyanate is also an efficient electrophile for hydroarylation of C=N bond. It provides a high atom- and step-economical method for the preparation

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• imine intermediates to produce chiral amines. Results and Discussion N-Chloramine formation N-(Di)alkyl-N-chloramines have been prepared in continuous organic–aqueous biphasic flow using either static mixers or a single-stage CSTR [26]. The choice of reactor and definition of tres for this reaction is

• ) over 42 hours, which proved unsuitable for continuous flow (Table 4, entry 1). Whilst KOt-Bu and NaOMe bases allowed rapid imine formation (Table 4, entries 2–6), though their low solubility in MeOH or toluene would require slurry pumping in flow mode which is undesirable. In addition, the isolation

• procedure is not straightforward, requiring multiple unit operations. To avoid this, a phase-transfer catalyst (TBAB) was used along with NaOH (Table 4, entries 7–9). This reagent, in a toluene/water mixture, promoted full conversion to imine 19 (Table 4, entry 8). The separation of the toluene phase

Selective formation of a zwitterion adduct and bicarbonate salt in the efficient CO₂ fixation by N-benzyl cyclic guanidine under dry and wet conditions

• Yoshiaki Yoshida,
• Naoto Aoyagi and
• Takeshi Endo

Beilstein J. Org. Chem. 2018, 14, 2204–2211, doi:10.3762/bjoc.14.194

• ). Characterization of zwitterion adduct 2 and bicarbonate salt 3 by FTIR-ATR and solid-state 13C-CPMAS NMR IR spectra of 2 and 3 were measured by FTIR-ATR methods (Figure 3). The two peaks were clearly observed at 1573 cm−1 and 1706 cm−1 due to carbonyl and imine moieties, respectively, in the spectrum of 2. On the

• bicarbonate and guanidinium moieties were observed at 161.3 ppm and 163.1 ppm, respectively, in the spectrum of 3. This chemical shift of 2 suggested that the electron density on the carbonyl carbon of 2 increased by the donation of an electron from the imine nitrogen, and also the electron at the iminium

• carbon was localized due to the imine structure stabilized by the direct binding with CO2. Therefore, both the peaks of carbonyl and iminium carbons in 2 shifted to higher magnetic field compared to that of 3. On the other hand, both the peaks of bicarbonate and guanidinium carbons in 3 were observed at

Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles

• James T. Fletcher,
• Matthew D. Hanson,
• Joseph A. Christensen and
• Eric M. Villa

Beilstein J. Org. Chem. 2018, 14, 2098–2105, doi:10.3762/bjoc.14.184

• et al. The efficiency of condensation between 4-formyltriazole and amine reactants as well as the propensity of imine products towards rearrangement was each strongly influenced by the substituent identity. It was observed that unsymmetrical condensation reactions conducted at 70 °C produced up to

• four imine products via a dynamic equilibrium of condensation, rearrangement and hydrolysis steps. Kinetic studies utilizing 1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carbaldehyde with varying amines showed rearrangement rates sensitive to both steric and electronic factors. Such measurements were

• facilitated by a high throughput colorimetric assay to directly monitor the generation of a 4-nitroaniline byproduct. Keywords: colorimetric assay; condensation; imine exchange; rearrangement; 1,2,3-triazole; Introduction Examples of multidentate chelators comprised of 1,2,3-triazole units have surged in