Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• by X-ray photoelectron spectroscopy (XPS). This residue was introduced by reductive amination of the DAT scaffold with the respective benzaldehyde derivative. In one compound (60% yield over three steps) the ALA unit is directly bound to the DAT as a relatively electron-withdrawing amide. In solution

• accessed in three steps from diethyl succinate according to Wu et al. [41]. Reductive amination with trifluoromethylated benzaldehyde was accomplished with a mixture of ZnCl2 and NaBH3CN [42] yielding the respective N-benzylated compound 2 in good yield. After subsequent N-Boc-deprotection with TFA

• electronically decoupled by introduction of a propylene spacer. Therefore, we started the synthesis with compound 5 (Scheme 2), which was accessed from compound 1 in two steps by reductive amination with N-Alloc-3-aminopropanal and subsequent N-Boc deprotection as reported recently [44]. Reductive amination with

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

• obtained as a diastereomeric mixture via an Ugi–Nenajdenko reaction using the 4-methyl-2,6,7-trioxabicyclo[2,2,2]octyl (OBO) ester 46 to avoid epimerization of the isocyanide, followed by a reductive amination and chromatographic separation of the isomers; a Passerini–Dömling IMCR led to the heterocyclic

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• -Chloro- and 2-bromocyclohexanone were synthetized as previously described [38][39], to provide cis-2-chloro (Cl) and cis-2-bromocyclohexylamine (Br), respectively, by a reductive amination [40]. To a sealed tube were added the corresponding ketone (10 mmol), ammonium acetate (100 mmol) and sodium

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• % yield in 17 steps from 16. The pyrrolidine nitrogen was then further derivatized with several small substituents (Scheme 7). Reductive amination with several aldehydes resulted in 3a–c. The N-methyl analogue 3d was synthesized via methylation with MeI. The methanesulfonamide 3e and acetamide 3f, in

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• protected naturally occurring amines such as GABA and phenylethylamine as well as diamines with orthogonal protecting groups, cf. product 2c. The combination of this protocol with the diastereoselective reductive amination reported by Hughes and Devine [41], provides access to very high value chiral α

Rational design of boron-dipyrromethene (BODIPY) reporter dyes for cucurbit[7]uril

• Mohammad A. Alnajjar,
• Jürgen Bartelmeß,
• Robert Hein,
• Pichandi Ashokkumar,
• Mohamed Nilam,
• Werner M. Nau,
• Knut Rurack and
• Andreas Hennig

Beilstein J. Org. Chem. 2018, 14, 1961–1971, doi:10.3762/bjoc.14.171

• synthesized according to a reported literature procedure [32], and then converted into the desired BODIPY anchor dye by reductive amination with the respective aldehyde using sodium triacetoxyborohydride as a mild reducing agent (route B) [36]. 3 was also synthesized by reductive amination by reacting BDP-NH2

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

• . Finally, a [1 + 1] macrocyclization between 4 and 5 was achieved by a reductive amination in a 1:1 CHCl3/MeOH mixture. A remarkable yield of 92% was obtained for this last step. As this kind of reductive amination has been proved to be under thermodynamic control, the resulting intermediate cage bearing

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

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

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

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

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

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

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

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• ready access to the two lactol isomers 29,30 in quantitative yield (≈1:1 ratio of isomers) [10][22][23]. Lactol isomers 29,30 could potentially serve as precursors for the formation of substituted piperidines via reductive amination or be oxidised to yield lactones or lactam derivatives. Conclusion

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• ., boron salts from reductive amination [4]. Hydrogenation offers a greener approach but is often only applicable to simple substrates due to chemoselectivity issues. An approach that has received much attention recently is the concept of hydrogen borrowing catalysis [5][6][7][8][9][10][11][12][13][14][15

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• were prepared by reductive amination of γ-aminophosphonyl ketones using sodium borohydride [41], or by conjugate addition of diethyl methylphosphonite to 2-cyclohexenone followed by Bucherer–Bergs amino acid synthesis [42]. Another synthetic approach for a series of α-fluorinated-γ-aminophosphonates

Experimental and theoretical investigations into the stability of cyclic aminals

• Edgar Sawatzky,
• Antonios Drakopoulos,
• Martin Rölz,
• Christoph Sotriffer,
• Bernd Engels and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 2280–2292, doi:10.3762/bjoc.12.221

• tetrahydroquinazoline core (Scheme 4b). Thus, anthranilic acid was alkylated by reductive amination with acetone and NaBH4 in two steps to yield the isopropyl-substituted derivative 14. The derivative 14 and the commercially available N-phenylanthranilic acid were converted to amides 15a,b under standard conditions

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• containing ON1 and four nucleobases in the presence of a DNA-template: a) TC; b) TG; c) TT; d) TA. The chromatograms were performed after reductive amination of the samples (for more details see Supporting Information File 1). Representative HPLC chromatograms obtained using elevated pH, for samples

• collected from first purification step (in Figure 4 marked with dashed line). The samples were collected from the reaction of ON1 and four nucleobases in the presence of a DNA-template: a) TC; b) TG; c) TT; d) TA. The chromatograms were obtained after reductive amination of the samples (for more details see

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• -von-Laue-Straße 7, D-60438 Frankfurt am Main, Germany 10.3762/bjoc.12.176 Abstract Starting from (S)-β-phenylalanine, easily accessible by lipase-catalyzed kinetic resolution, a chiral triamine was assembled by a reductive amination and finally cyclized to form the title compound 10. In the crystals

• reductive amination to form 18 (58%). After removal of the Boc protecting group (quant.), triamine 19 was reacted with dimethyl trithiocarbonate in refluxing nitromethane. The thiourea intermediate was activated in situ by S-alkylation with MeI. Upon further heating the final cyclization occured forming the