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

Coordination-driven self-assembly vs dynamic covalent chemistry: versatile methods for the synthesis of molecular metallarectangles

• Li-Li Ma,
• Jia-Qin Han,
• Wei-Guo Jia and
• Ying-Feng Han

Beilstein J. Org. Chem. 2018, 14, 2027–2034, doi:10.3762/bjoc.14.178

• have reported a suite of [2 + 2] tetranuclear metallarectangles, each formed using dinuclear molecular clips and pyridyl-based donor ligands [6][7][8][9][31][32][33][34][35][36]. The introduction of dynamic covalent bonds (such as imine C=N bonds), could allow the multicomponent assembly of such

• metallarectangle structures in one-pot reactions, thereby reducing both waste and the number of reaction steps. In this work we successfully combine coordination-driven self-assembly and dynamic covalent chemistry through imine bond formation between amines and 4-formylpyridine to construct the desired rectangular

• . Similar to that observed in complex 3a, a peak at m/z = 450.0868 was observed, which is attributable to [3b − 4OTf]4+, and its isotopic pattern is in good agreement with the theoretical distribution (Figure 3, right). The absorption band at 1620 cm−1 in the IR spectrum indicated the existence of an imine

Chiral bisoxazoline ligands designed to stabilize bimetallic complexes

• Deepankar Das,
• Rudrajit Mal,
• Nisha Mittal,
• Zhengbo Zhu,
• Thomas J. Emge and
• Daniel Seidel

Beilstein J. Org. Chem. 2018, 14, 2002–2011, doi:10.3762/bjoc.14.175

• available. This led to the selection of naphthyridine, pyridazine, pyrazole, and phenol building blocks. We opted to connect these linkers to oxazolines via amide bonds. The reasoning for this was twofold. Firstly, this should provide ligands with significantly improved stabilities over for instance imine

A hemicryptophane with a triple-stranded helical structure

• Augustin Long,
• Olivier Perraud,
• Erwann Jeanneau,
• Christophe Aronica,
• Jean-Pierre Dutasta and
• Alexandre Martinez

Beilstein J. Org. Chem. 2018, 14, 1885–1889, doi:10.3762/bjoc.14.162

• three imine functions is highly sable [12][13]. Hydrogen bonds between the amide group and the formed imine function could account for the high stability of this intermediate, shifting the equilibrium between the different oligomers and the cage in favor of this latter (vide infra). 1H NMR of cage 1 The

• another arm can account for this helical structure (Namine···Namide distances of 2.97 Å). This structure sheds light on the excellent yield achieved in the last step of the synthesis. Indeed, such intramolecular hydrogen bonding probably also occurred in the imine precursor, accounting for its high

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• to the triple bond of 22 to give the intermediate 26, followed by the reductive elimination of the trivalent iodine motif to afford the palladium-vinylidene 27. This would undergo a nucleophilic addition of the imine and a subsequent proto-demetallation to give enamine 29. A series of rearrangements

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• fused between two benzene rings. A range of compounds with interesting biological or photophysical properties contain the phenoxazine core, where the amine moiety is either functionalized or oxidized to the corresponding imine [1][2][3][4]. Phenoxazine derivatives can display antitumor activity [5][6][7

Recent advances in phosphorescent platinum complexes for organic light-emitting diodes

• Cristina Cebrián and
• Matteo Mauro

Beilstein J. Org. Chem. 2018, 14, 1459–1481, doi:10.3762/bjoc.14.124

• neutral imine substitutes in an attempt to further improved the stability and the performances of their N···H–C stabilized phosphors (Figure 5) [34][35]. Either when one, compound 10 [34], or two, compound 11 [35], carbene moieties were used, the resulting platinum compounds were basically nonemissive in

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• to 6a (possibly tautomerized from its imine isomer) [69]. Finally, the β-trifluoromethylated enamine 6a undergoes intramolecular azirination affording the corresponding β-trifluoromethylated 2H-azirine via a known pathway [56][57]. Conclusion In summary, we have reported an efficient hypervalent

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• our group. These were applied to the asymmetric alkylation reaction of benzophenone imine of glycine ester which has become one of the benchmark reactions for examining the performance of new phase-transfer catalysts [36]. Later in 2010, Shirakawa and Shimizu reported the synthesis of novel inherently

• reactions, optically active calix[4]arene-imine derivative 92 containing an L-prolinamide functionality was also tested as a catalyst for enantioselective aldol reactions between 70 and a variety of aromatic aldehydes 72. The anti-aldol adducts were obtained in high yields and ees (Scheme 26). Based on the

• skeleton, an L-prolinamide analogue was prepared as a model catalyst from p-butoxybenzenamine. Without calix[4]arene backbone, only 9% ee was obtained. It was also proposed that the observed enantioselectivity resulted from the approach of the enamine double bond to the Re face of the imine via a stable

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• nucleophiles, thus increasing the structural diversity of the resulting products. The first asymmetric catalytic versions were reported only in the 2010s despite tremendous achievements in catalytic asymmetric imine addition reactions [20][21][22]. Ever since, a number of catalytic asymmetric nucleophilic

• ]. An extensively used two-component variant of this reaction consists in using a preformed imine. Among chiral metal complexes, a wide variety of organocatalysts [26][27][28][29][30][31][32][33][34] has been used to promote asymmetric Mannich reactions. Among them, cinchona alkaloid 1 was employed in

• -donating and electron-withdrawing groups. The lowest yield (51%) was obtained in the reaction of a fluorinated isatin imine (R1 = Me, R2 = 7-F). The utility of this methodology was demonstrated by its application in the formal synthesis of the anticancer agent AG-041R. Furthermore, several of the formed

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• with benzophenone imine and subsequent hydrogenolysis. Keywords: aminoestrones; Buchwald–Hartwig amination; 13α-estrone; functionalization; microwave assisted reactions; Introduction Aminoestrones are of particular interest thanks to their diverse biological applications [1][2][3][4]. There exist

• derivative [17][18]. The C(sp2)–N cross-coupling of the triflate was achieved with benzophenone imine or benzylamine. The removal of the protecting groups resulted in 3-aminoestrone in high yields. Schön et al. developed two convenient protocols for the preparation of 3-aminoestrone using Pd(OAc)2 and Pd2

• -13α-estrone (13). The efficient C(sp2)–N coupling method elaborated above proved to be suitable for the reaction of 2-bromo-3-benzyl ether 2 and benzophenone imine as an amine precursor (Scheme 2). The deprotection was achieved by hydrogenolysis using a Pd/C catalyst. The resulting newly-synthesized 2

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• , there are certain bonds like imine, oxime, hydrazone, orthoester, acetal, vinyl ether and polyketal [103] that are known to undergo hydrolysis at acidic pH, while being extremely stable during blood circulation. Therefore, acid-labile bonds could be hydrolyzed in the slightly acidic microenvironment and

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• alkenylation reaction of pivalophenone N–H imine with an alkenyl phosphate. The reaction tolerates various substituted pivalophenone N–H imines as well as cyclic and acyclic alkenyl phosphates. Keywords: alkenylation; C–C bond formation; C–H activation; cobalt; imine; Introduction Transition-metal-catalyzed

• -directed arene C–H alkenylation reaction with alkenyl phosphates using a different cobalt–NHC catalyst (Scheme 1b) [28]. Meanwhile, we have also demonstrated that pivaloyl N–H imine serves as a powerful directing group for cobalt-catalyzed arene C–H functionalization reactions such as the hydroarylation of

• alkenes and alkylation/arylation using organic halides [29][30]. These previous studies have prompted us to expand the scope of cobalt catalysis for the C–H alkenylation and thus to develop an ortho C–H alkenylation reaction of pivalophenone N–H imine with alkenyl phosphates using a new cobalt–NHC

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• respect to the use of an enantiomeric cyclic imine in this type of reaction [83]. The formation of the possible naphthoxazino-quinoxalinone diastereomers 46 was investigated and studied by theoretical calculations (Scheme 5). In this and all previous cases, the conformational behaviour of the

Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• in 64% and 58% yield, respectively. Substituted styrenes and 1-ethynylbenzene were also tolerated well, giving corresponding products 3ai–3aj in 45–50% yields. The formations of 3ah–3aj likely derives from an azo-Diels–Alder reaction of styrene or ethynylbenzene with an imine intermediate, in situ

• gives imine intermediate product 5, which was detected by TLC and GC–MS. Moreover, when separated synthesized 5 was subjected to react with 2a, the corresponding product 3aa was isolated in 89% yield. These control experiments indicate that 5 is a possible reaction intermediate. Based on these control

• homogeneous reaction with N-arylglycine esters, N-iodo intermediate 4 was generated. Eliminating a molecule of HI affords imine intermediate 5. In the presence of acetic acid, the protonated 5-H+ undergoes nucleophilic addition with C–H nucleophiles 2 to give the desired products 3. Conclusion In summary, an

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• as ABT-737 [28]. As shown in Scheme 11, the key step of this synthesis was a highly diastereoselective zinc-mediated aza-Reformatsky reaction of methyl bromoacetate (9d) with enantiopure N-tert-butylsulfinyl imine 29. It led to the corresponding chiral β-amino ester 30 in both high yield (85%) and

• diastereoselective aza-Reformatsky-type carbethoxyallylation of (S)-N-tert-butylsulfinyl imine 25u with bromide 35 performed in isopropanol as solvent in the presence of zinc, LiCl and K2CO3, which afforded the corresponding chiral acrylic ester 36 as single diastereomer (98% de) in 82% yield (Scheme 14). However

• halofluoroacetate. When the opposite enantiomer of the ligand (1S,2R)-59 was used under the same reaction conditions, it provided the corresponding (3R,4S) product 62a in 70% yield and 90% ee starting from the corresponding imine 60a (Scheme 23). Unfortunately, the scope of this domino Reformatsky/cyclization

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• , isolated imine intermediate 30 under similar conditions provided 4-substituted pyrazolo[3,4-b]pyridine 31 in DMF (Scheme 5). This intramolecular coupling reaction provided highly efficient synthetic procedure for the design and synthesis of pyrazolo[3,4-b]pyridine-nucleus-based pharmacological agents with

• in situ intramolecular cyclization of 5-aminopyrazole-4-caroxylate 35 with β-haloaldehydes 36 via the corresponding imine derivative was carried out in presence of Pd(PPh3)2Cl2 (1.0 mol %), Cu2O (1.0 mol %), 1,10-phenanthroline (2.0 mol %), TBAI (6 mol %), by Batra et al. [50] to generate the

Synthesis and spectroscopic properties of β-meso directly linked porphyrin–corrole hybrid compounds

• Baris Temelli and
• Hilal Kalkan

Beilstein J. Org. Chem. 2018, 14, 187–193, doi:10.3762/bjoc.14.13

• -porphyrin, β-corrole-linked hybrid structure described a Suzuki–Miyaura cross-coupling reaction between a β-borylated corrole and meso-bromoporphyrins (Scheme 1D) [37]. Recently, we have successfully synthesized meso–meso and β-meso-linked imine-bridged porphyrin–corrole conjugates and investigated

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• formation of 1,3,4-thiadiazoles (Scheme 34) [69]. Again, the sulfur anion is photooxidized by Eosin Y to produce a thiyl radical intermediate. Aerobic oxidation regenerates the photocatalyst and forms a superoxide radical anion. Subsequent thiyl radical addition to the imine moiety forms the five-membered

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols

• Xinyun Liu,
• Johnny H. Phan,
• Benjamin J. Haugeberg,
• Shrikant S. Londhe and
• Michael D. Clift

Beilstein J. Org. Chem. 2017, 13, 2895–2901, doi:10.3762/bjoc.13.282

• Xinyun Liu Johnny H. Phan Benjamin J. Haugeberg Shrikant S. Londhe Michael D. Clift Department of Chemistry, The University of Kansas, 2010 Malott Hall, 1251 Wescoe Hall Drive, Lawrence, KS, 66045, United States 10.3762/bjoc.13.282 Abstract A new method for imine synthesis by way of quinone

• -catalyzed oxidative deformylation of 1,2-amino alcohols is reported. A wide range of readily accessible amino alcohols and primary amines can be reacted to provide N-protected imine products. The methodology presented provides a novel organocatalytic approach for imine synthesis and demonstrates the

• preparation of imines (Scheme 1). The condensation of an amine with an aldehyde or ketone is the oldest and most commonly employed method for imine synthesis [4]. More recently, the catalytic dehydrogenation of amines mediated by metal and organic catalysts has begun to emerge as an alternative approach for

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• iminyl anion 19. After protonation and hydrolysis of the imine function, the α-trifluoromethylated ketones 16 were obtained in moderate to good yields (Scheme 8) [27]. Alkenyl MIDA (N-methylimidodiacetic) boronates 20, as functionalised alkenes, were transformed into α-trifluoromethyl-α-boryl ketones 21

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• salts 27 in equilibrium with their tautomeric imine form 28 (Scheme 18). Depending on the nature of the substituent R, the enamine or the imine form predominated (Table 3) [33]. In 2004 Mazurkiewicz and Fryczkowska discovered that the same type of compounds can be obtained in good or even very good

• ylide resonance structures. Furthermore, the authors did not observe an imine tautomeric form of the synthesized compounds as described by Schweizer (1H NMR). The isotopic exchange of acidic protons using a D2O solution in CD3CN revealed that the isotopic exchange of a proton in the α-position was

• for the synthesis of 2-aminovinylphosphonium salts 30 by reaction of (formylmethyl)triphenylphosphonium chloride (29) with aromatic amines in isopropanol in yields of 47–91% (Scheme 21). The initially obtained imine form of the product underwent tautomerization to a more stable enamine form, usually