One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• α,β-unsaturated aldehyde 71. A series of reductive amination and amidation reactions then led to the formation of the targeted substituted benzo[7]annulene 72 (Scheme 13). Moreover, the structure–activity study revealed that some of the compounds showed nano- to subnanomolar IC50 values on αvβ3 and

• reported that the oxidative amination of 2,3-benzotropone (12) with methylcopperamine sulfate in aqueous methylamine at room temperature afforded 4-methylamino-1-naphthalene carbaldehyde (215) with a trace amount of 4-methylamino-2,3-benzotropone (214) via reaction paths including the dishing of Michael

Hypervalent iodine(III)-mediated decarboxylative acetoxylation at tertiary and benzylic carbon centers

• Kensuke Kiyokawa,
• Daichi Okumatsu and
• Satoshi Minakata

Beilstein J. Org. Chem. 2018, 14, 1046–1050, doi:10.3762/bjoc.14.92

• applications have not been explored. We recently reported on the decarboxylative Ritter-type amination of carboxylic acids containing an α-quaternary carbon center using a combination of PhI(OAc)2 and I2 to produce the corresponding α-tertiary amine derivatives (Scheme 1) [25]. Mechanistic investigations

Preparation, structure, and reactivity of bicyclic benziodazole: a new hypervalent iodine heterocycle

• Akira Yoshimura,
• Michael T. Shea,
• Cody L. Makitalo,
• Melissa E. Jarvi,
• Gregory T. Rohde,
• Akio Saito,
• Mekhman S. Yusubov and
• Viktor V. Zhdankin

Beilstein J. Org. Chem. 2018, 14, 1016–1020, doi:10.3762/bjoc.14.87

• efficient electrophilic atom-transfer reagents useful for conversion of various organic substrates to the corresponding products of azidation [7][8][9][10][11], amination [12][13], cyanation [14][15][16][17], alkynylation [18][19][20], or chlorination [21][22]. Recently, Zhang and co-workers reported the

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

• desired products have been obtained in good to excellent yields. The nature and the position of the aniline substituent at the aromatic ring influenced the outcome of the couplings. 2-Amino-13α-estrone was also synthesized in a two-step protocol including an amination of 2-bromo-13α-estrone 3-benzyl ether

• 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

• application of a Pd-catalyzed Buchwald–Hartwig amination. In recent years, extensive efforts have been made on the Pd(0)-catalyzed amination of aryl halides or triflates in order to achieve the efficient synthesis of substituted anilines [6][7][8][9]. Buchwald et al. stated that the Pd source is determining

Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• pathways. For example, Liu and co-workers used Togni’s benziodoxolone reagent [35] in a radical-mediated vicinal 2,3-difunctionalization of allenes, which proceeded via CF3-radical adduct A (Scheme 1a) [36]. In contrast, Muñiz reported that with PhI(NTs2)2, an oxidative amination occurred via cation B

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• recycling, minimizing the amount of the used organic solvent and generated waste [67]. The same group reported another interesting catalytic micelle system, which is based on PTS (polyoxyethanyl α-tocopheryl sebacate) [68]. Using PTS-based micelles, they showed the amination of allylic ethers in water

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• to Vasellas' procedure [31][32] – with benzylamine under the reductive amination conditions afforded an inseparable mixture of two products differing in the configuration at the C2 center (12a and 12b; Scheme 2); such a phenomenon – epimerization under these conditions – is known [33]. The

• from the C6’-position gave alcohol 22 in 97% yield. Under the same "Swern oxidation–reductive amination–acetylation" conditions, alcohol 22 was converted into aldehyde 23, which reacted further with amine 18, furnishing diolefin 24 in 64% total yield. Cyclization of precursor 24 induced by the Hoveyda

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• prepare compound 6. It is well known that the direct one-step reductive amination of 6 to give 12 can be accomplished by simple heterogeneous reduction with H2/Raney-nickel [24]. However, THF is employed in all of our prior flow steps and is a poor choice as a solvent for the reductive amination step due

• to limited solubility of ammonia in THF. H2/Raney-nickel reductions are often carried out in alcoholic media where much higher concentrations of ammonia are achievable but would require a solvent exchange. There are many reports of continuous-flow chemistry methods for reductive amination of ketones

•  2, entries 1–6). Optimization of the flow rate with 1 M concentrations of each reactant (Table 2, entries 6–8) showed that a flow rate of 1.0 mL min−1 (tR = 20 min) was optimal, giving an isolated yield of 78% (Table 2, entry 7). The reductive amination of 11 performed in the first generation batch

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

• formed by addition from the less sterically hindered amino group. The free amino group was alkylated by reductive amination on reaction with substituted aldehyde or ketones to provide the corresponding pyrazolo[1,5-a]pyrimidine derivatives 139 (Scheme 39). The pyrazolo[1,5-a]pyrimidine derivatives 139

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• starting aldehyde 2 was subjected to a reductive amination with aminoacetaldehyde dimethyl acetal and NaBH4, followed by N-tosylation and hydrochloric acid-mediated cyclization under concomitant N-detosylation and aromatization. Direct ring metalation of 3 with TMPMgCl∙LiCl was performed as described by us

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• ]. Protocols using water/isopropanol [3], optimally coordinated triols [4][5], and hexafluoroisopropanol (HFIP) [6][7] as the corresponding hydrogen bond donors have shown considerable success. This mode of activation has been demonstrated for amination [3][4][5] and Friedel–Crafts reactions [6][7] on benzylic

• C–F amination reactions employing water/isopropanol [3] and triols [4][5] as hydrogen-bond donor activators. Through these studies, the authors suggested that multiple donors (even when using a triol) surround the fluorine atom of the benzyl fluoride, thus stabilising the transition state through

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• functionalized carbohydrates (Figure 1c). Various types of reaction, such as reductive amination [32], oxime formation [33], amidation [34], and perfluorophenyl azide (PFPA) photocoupling [35][36], have been used to functionalize the surface of AuNPs with carbohydrates. The detailed information regarding the

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• local anesthetics: (a) a lipophilic aromatic ring, (b) an amide (or ester) linker, and (c) a terminal tertiary amine [9]. The original synthesis of these bioactive compounds involved a Perkin condensation followed by an amination reaction. An alternative pathway to AL-12B has been described by Couture

• [41], followed by amination [42] furnishes the desired target compounds. The amino group is introduced in the final step as it would otherwise interfere with the desired photoreaction. In fact, amines are very potent electron donors and are easily oxidized by the excited phthalimide chromophore [43

• ring and the olefinic =CH group (see Supporting Information File 1). The final amination step was achieved following a modified procedure by Marzabadi and co-workers [42]. Catalytic amounts of potassium iodide were added for in situ halogen exchange. The dehydrated products 7a–q were heated in the

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• , oxidation of the secondary alcohol with pyridinium dichromate into the corresponding cyclopentanone derivative and subsequent olefination using CBr3F gave the monofluoroalkene 96 with a modest selectivity towards the (Z)-alkene. A Negishi coupling then gave alkene 98. Stereoselective reductive amination

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• propargylamines by nucleophilic addition. The synthesis of propargylamines by diastereoselective reductive amination requires alkynyl ketones, which are difficult to prepare and are unstable towards reductive conditions. In approach I, organometallic nucleophiles are added to N-sulfinyl propargylimines, derived

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• to provide the desired 2-aminoheptenoic acid derivative 11. Several syntheses of this important amino acid have appeared which include Lubell’s palladium-catalyzed allylation [15], Riera’s asymmetric epoxidation protocol [16], Rich’s enolate amination [17] and Hruby’s asymmetric alkylation [18] of a

An efficient synthesis of a C₁₂-higher sugar aminoalditol

• Łukasz Szyszka,
• Anna Osuch-Kwiatkowska,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2017, 13, 2146–2152, doi:10.3762/bjoc.13.213

• building blocks. The synthesis was realized by a regioselective introduction of the azide group and subsequent protection–deprotection transformations. The chemical reactivity of the aminoalditol was tested in the reductive amination reaction with a selectively protected sucrose monoaldehyde. Keywords

• : higher carbon sugars; reductive amination; sucrose; Introduction Carbohydrates, because of their availability in a variety of optical pure forms, are particularly useful in planning and executing the synthesis of chiral macrocyclic compounds [1][2][3][4][5]. In this context, polyhydroxylated derivatives

• ][20]. Our synthesis towards a sucrose derivative with a long alditol pendant was initiated from aldehyde 12 (readily prepared from the known [15] alcohol 11 with the free 6-OH group) and C12-aminoalditol 10 (Scheme 2). Coupling of these two species under the reductive amination conditions provided

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• (II) acetate-catalyzed aerobic oxidative amination and it proceeds through a tandem Michael addition followed by an intramolecular oxidative amination. Therefore, our target molecules A could be synthesized by the oxidative coupling of 2-aminopyridines with α,β-unsaturated ketones B, themselves easily

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• PEG with tosyl, bromide, thiol, carboxylic acid or amine functionalities in good to quantitative yields and with no polymer chain oligomerization, proving the versatility of the method. Keywords: amination; bromination; carboxylation; mechanochemistry; poly(ethylene glycol); solid state; thiolation

Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• . Compound 18 (Scheme 7) was generated via a double reductive amination, in analogy to the syntheses of compounds 9a–q. Because none of the aromatic rings contained any activating group, the cyclization was performed with 70% HClO4 as catalyst. However, in the experimental conditions used it was not possible

• between ring formation in para- or meta-position to an activating group such as a methoxy group, when both were possible. For this, compound 22 (Scheme 8) was synthesized via a double reductive amination, as per synthesis of 9a–q. As expected, when the precursor was treated with 6 M HCl, the cyclization

• procedures were followed unless indicated otherwise. Some representative examples of spectroscopic data are reported below. The complete sets of data are reported in Supporting Information File 1. General method for the double reductive amination reaction NaBH(OAc)3 (3.3 g, 15 mmol) was added to a stirring

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• the first step, and then carry out the amination reaction in the second step using the appropriate ammonia source (Scheme 11a). As a test reaction, the amination of 1-[(4-bromophenyl)thiocarbamoyl]benzotriazole (27d) in ammonia vapours by the so called aging or vapour digestion was selected. It was

• absorption bands of N-(4-bromophenyl)thiourea (32d) at 1617 and 509 cm−1. Several other thiocarbamoyl benzotriazoles were also quantitatively transformed to primary thioureas by this method. For the purpose of performing the amination reaction in a ball mill, ammonia gas was generated in situ by milling the

• thiocarbamoyl substrate with a mixture of sodium carbonate and ammonium chloride. This mixture released ammonia gas during milling and allowed the amination reaction to take place under solvent-free mechanochemical conditions. Following a simple aqueous work-up and filtration, the desired primary thioureas 32

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• most important field of application of this catalytic principle. Based on several highly spectacular recent reports, we thus wish to discuss some of the most important achievements in this field within the context of this review. Keywords: amination; chlorination; fluorination; hydroxylation

• precursors and carry out the direct α-amination with a suitable electrophilic N-transfer reagent in the presence of a chiral catalyst to ensure an efficient face-differentiation in the C–N bond formation. This strategy has been investigated under chiral phase-transfer catalysis in the past and the results

• have been rather promising, as will be discussed in the following chapter [61][138][139][140]. One of the key-questions in this field is the nature of the electrophilic N-transfer reagent. One class of reagents that has been employed for α-amination reactions for almost one century now are

New electroactive asymmetrical chalcones and therefrom derived 2-amino- / 2-(1H-pyrrol-1-yl)pyrimidines, containing an N-[ω-(4-methoxyphenoxy)alkyl]carbazole fragment: synthesis, optical and electrochemical properties

• Daria G. Selivanova,
• Alexei A. Gorbunov,
• Olga A. Mayorova,
• Alexander N. Vasyanin,
• Igor V. Lunegov,
• Elena V. Shklyaeva and
• Georgii G. Abashev

Beilstein J. Org. Chem. 2017, 13, 1583–1595, doi:10.3762/bjoc.13.158

• ], Ullmann coupling [13][14], Buchwald–Hartwig amination [15] or N-alkylation of carbazole in the presence of alkali metal carbonates under MW irradiation [16]. In our case, the N-arylation was realized under phase transfer conditions using triethylbenzylammonium chloride (TEBA) as a catalyst [17][18

Nitration of 5,11-dihydroindolo[3,2-b]carbazoles and synthetic applications of their nitro-substituted derivatives

• Roman A. Irgashev,
• Nikita A. Kazin,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2017, 13, 1396–1406, doi:10.3762/bjoc.13.136

• of acetyl nitrate. Therefore, attempts to enhance yields of compounds 3 by using large amounts of acetyl nitrate have proved to be unsuccessful. Notably, 2,8-diamino-substituted ICZ derivatives have previously been prepared by using the Buchwald–Hartwig amination of the corresponding 2,8-dibromo-ICZs

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• starting material to produce primary, secondary and tertiary C-glycoside glycamines, including mono- and disaccharide structures. The semisynthetic approach utilized was generally based on polysaccharide-controlled hydrolysis followed by reductive amination. All reactions were conducted in aqueous media

• and without the need of hydroxyl group protection. We were able to identify optimal conditions for the reductive amination of agar hydrolysis products and to overcome the major difficulties related to this kind of reaction, also extending it to reducing anhydrosugars. The excess of ammonium acetate

• , methyl- or dimethylamine, and the use of a diluted basic (pH 11) reaction media were identified as important aspects to achieve improved yields, as well as to decrease the amount of byproducts commonly related to reductive amination of carbohydrates. This strategy allowed the transposition of the 3,6