Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• -methylpregabalin (1) in an analogy to literature procedures (Scheme 4) [47]. Adduct 7 was transformed to lactone 13 via nitro group reduction with NaBH4/NiCl2 followed by spontaneous lactamization. In the last step, lactam 13 was hydrolyzed and decarboxylated to give 4-methylpregabalin hydrochloride (1·HCl). We

An alternative to hydrogenation processes. Electrocatalytic hydrogenation of benzophenone

• Cristina Mozo Mulero,
• Alfonso Sáez,
• Jesús Iniesta and
• Vicente Montiel

Beilstein J. Org. Chem. 2018, 14, 537–546, doi:10.3762/bjoc.14.40

• electrolyte upon the conversion and product yield of the electrochemical hydrogenation of benzophenone is explored. Results and Discussion Pd nanoparticles supported on Vulcan XC72R as electrocatalyst in cathodic reaction (electrocatalytic hydrogenation) were synthesised by reducing K2PdCl4 using NaBH4 in a

• using NaBH4 as reducing agent in a water-in-oil (w/o) microemulsion in the presence of polyethylene glycol hexadecyl ether, Brij@30 as capping agent and n-heptane as organic solvent (water/Brij@30/n-heptane). After precipitation and copiously washing with acetone and water, Pd nanoparticles were

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• used for the hydrogenation of fatty acids). In comparison to the Wolff–Kishner reaction, the use of hydrazine is replaced by the use of hydrogen gas, which can be seen as a double-bladed knife. The reduction step can also be performed with NaBH4 or other reductants. At the moment, a complete and clear

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

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• 62 (Scheme 8) [118]. To this end, GlcN hemiacetal 61 was reduced by treatment with NaBH4, the acetamido group was removed with barium hydroxide, and the resulting amine was transformed into azide 62. The primary alcohol in 62 was regioselectively protected as silyl ether, followed by benzylation and

Conformational preferences of α-fluoroketones may influence their reactivity

• Graham Pattison

Beilstein J. Org. Chem. 2017, 13, 2915–2921, doi:10.3762/bjoc.13.284

• atoms on the reactivity. The reactivity of α-fluoroacetophenone was compared to α-chloro- and α-bromoacetophenone in sodium borohydride reductions, using 0.2 equiv of NaBH4 to 1.0 equiv of α-fluoroacetophenone and 1.0 equiv of the second α-haloacetophenone to ensure the reaction stopped at low

• that additions to this conformation lead to the most stabilized transition state [17], whilst experimentally, nucleophilic addition of NaBH4 to 2-fluoropropiophenone leads to the anti-diastereoisomer that would be expected by polar Felkin–Anh addition to this conformation [18]. However, around a 90

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• (Scheme 3). Compound 2c was dissolved in a mixture of acetic acid and NaBH4, cooled to 0 °C to afford the highly functionalized (+/−)-streptopyrrolidine analogue 6 in 70% yield as a unique diastereomer. Streptopyrrolidine was isolated from the marine bacterium Streptomyces sp. and has exhibited a

Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

• Artur Jabłoński,
• Yannic Fritz,
• Hans-Achim Wagenknecht,
• Rafał Czerwieniec,
• Tytus Bernaś,
• Damian Trzybiński,
• Krzysztof Woźniak and
• Konrad Kowalski

Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249

• ; found: C, 73.57; H, 4.40; N, 17.77. Synthesis of compound 4 To a stirred solution of compound 2 (268 mg, 0.7 mmol) in THF (20 mL) was added NaBH4 (38 mg, 1.0 mmol) at room temperature. After 30 minutes the reaction mixture was poured into water (≈30 mL), extracted with chloroform (≈40 mL), dried over

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

• to avoid nucleophilic substitution of the halide at a late stage, we decided to start the synthesis with 4-azidobutanal, which was prepared by opening THF with iodine and NaBH4, nucleophilic substitution by sodium azide and Swern oxidation of the alcohol. 4-Azidobutanal was converted with chiral

• should be reduced. However, all attempts to reduce the isolated azide 7wx with NaBH4 or PPh3 failed, due to the competing triazole formation. Therefore, instant reduction of in situ prepared 6wy was envisaged. The nucleophilic addition of (trimethylsilyl)ethynyllithium to N-sulfinylimine 5w was monitored

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• agent used. Thus, the reaction of 3,6-diketones with K-selectride was shown to afford 3α-hydroxy-6-ketones [31]. On the other hand, treatment of the diketone 31 with NaBH4 followed by acetate deprotection led to 24-epiteasterone (34) having a 3β-hydroxy group on the A-ring (Scheme 7). 2α-Hydroxy-3

• , NaI, DMF, 150 °C (83%); (c) KOH, MeOH, 65 °C (96%). (a) MCPBA, CH2Cl2, 20 °C (90%); (b) NBS, DME, 20 °C; (c) KOH, MeOH, 20 °C (85% over 2 steps). (a) BnBr, DMAP, Bu2SnO, TBAI, DIPEA, 110 °C (94%); (b) PCC, CH2Cl2, 20 °C (84%); (c) H2, Pd/C, 20 °C (99%); (d) NaBH4, EtOH, −25 °C (61%); (e) KOH, MeOH, 65

• °C (96%). (a) TsCl, DMAP, Py, 30 °C (91%); (b) Py, 115 °C (65%); (c) KOH, MeOH, 20 °C (52%). (a) NaBH4, EtOH, −25 °C (49%); (b) KOH, MeOH, 65 °C (85%). (a) Anisaldehyde, TMSCl, MeOH, 20 °C; (b) BnBr, DMAP, Bu2SnO, TBAI, DIPEA, 110 °C (86% over 2 steps); (c) PCC, CH2Cl2, 20 °C (81%); (d) H2, Pd/C, 20

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

• mixture of two anomers (α:β = 2:1). Treatment of azido ester 5 with NaBH4 gave predominantly azidodiol 6 (66%) and small amounts of aminodiol 7 (5%). Application of LiAlH4 as the reducing agent afforded only compound 7 (Scheme 1). The former result may open, eventually, a new possibility for the

• , 1260.5561; Anal. calcd for C77H79N3O12: C, 74.61; H, 6.51; N, 3.39; found: C, 74.70; H, 6.58; N, 3.38. Preparation of compounds 6 and 7 Method a: To a solution of 5 (0.23 g, 0.18 mmol) in THF/methanol (3:1 v/v, 30 mL), NaBH4 (3 g, 79 mmol) was added in few portions and the mixture was stirred for 3 h at 20

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

• Yoko Hamada,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 1507–1512, doi:10.3762/bjoc.13.149

• trifluoroacetate at −80 °C, a Horner–Wadsworth–Emmons reagent [17] activated by LiBr and Et3N [18][19][20] was introduced to this solution at room temperature, leading to the formation of (E)-6 after the NaBH4 reduction of the resultant products (see Supporting Information File 1 for the detailed procedure). As

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• reduced with NaBH4 under standard conditions. Compound 18 was prepared for comparison of the analytical data with that of compound 15. Although the IR spectra look fairly similar, the two isomers can be distinguished from their NMR spectra, in particular the 1H and 13C signals of the atoms in 2 and 3

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

• data retrieved from literature [25]. Overview of the hydrolysis–reductive amination procedure to produce primary glycamine 3 and byproducts. Overview of synthetic procedures, yields and specific rotation of glycamines 3, 7, 8, epi-8, 9 and 13. a) 0.1 M TFA, 80 °C; b) NaBH4; c) 2.0 M TFA, 110 °C; d

Sugar-based micro/mesoporous hypercross-linked polymers with in situ embedded silver nanoparticles for catalytic reduction

• Qing Yin,
• Qi Chen,
• Li-Can Lu and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 1212–1221, doi:10.3762/bjoc.13.120

• an excess amount of NaBH4 as the reducing reagent [45]. In our study, the process of the catalytic reaction was readily followed as the color of the solution turned from yellow to colorless. Both the reactants and products are easily monitored by UV–vis spectroscopy without any formation of

• absorption peak at 317 nm of observed for the neutral 4-NP solution, the absorption at 400 nm is attributed to the 4-nitrophenolate ion. The latter is generated through deprotonation of 4-NP (pKa = 7.15) upon the addition of NaBH4 [41]. As can be seen from Figure 5a, the absorption peak of the substrate

• of 4-NP at time t, and k is the first-order rate constant. Figure 5b shows the ct/c0 and ln(ct/c0) changes with time for the reduction of 4-NP in the presence of NaBH4 with the AgNPs/SugPOP-1 composite as catalyst. By the Beer–Lambert law we find that ct/c0 is proportional to At/A0. At/A0 was

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• Penadès and co-workers [15] is a modified Brust–Shiffrin method [17], based on the in situ Au3+ reduction by means of NaBH4 in the presence of thiol-ending neoglycoconjugates. Following this approach, a rapid synthesis of AuNPs characterized by elevated glycan density on the NP surface and a 1–10 nm

• simply mixing at room temperature Au3+ salts and thio-glucoside as reducing and stabilizing agents, without the addition of NaBH4 [19]. The two-step synthetic procedure consists in the initial synthesis of AuNPs stabilized by temporary compounds (i.e., citrates, amines or phosphines), followed by the

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• the latter with K3PO4 generates the alkyl selenolate anion (RSe−) which reacts with another RSeCN molecule to give the corresponding diselenide R2Se2. Reduction of the latter diselenide by treatment with NaBH4 affords an alkyl selenolate anion, which reacts with styryl halide to give the desired

Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif

• Tetiana Bykova,
• Nawaf Al-Maharik,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72

• h, rt, 30%; c) Et3N·3HF (10 equiv), 4 days, 120 °C, 30%; d) NaBH4 (10 equiv)/NiCl2·6H2O (5 equiv), MeOH, 1 h, 0 °C, 18 h, rt, 50%; e) 10% Pd/C (10 mol %), H2, Et3N/CHOOH: molar ratio 1:37, THF, 18 h, rt, 78%. Reagents and conditions: a) Et3N·3HF (8 equiv), 18 h, 140 °C; b) Tf2O (4 equiv), pyridine

• , 1 h, 0 °C, 3 h, rt, 40% (10b), 15% (10c); c) Et3N·3HF (10 equiv), 4 days, 120 °C, 51% (11b), 31% (11c); d) NaBH4 (10 equiv)/NiCl2·6H2O (5 equiv), MeOH, 1 h, 0 °C, 18 h, rt, 65% (5b), 23% (5c). Reagents and conditions: a) terephthaloyl chloride (1 equiv), Et3N (4 equiv), DMAP (20 mol %), DCM, 18 h

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• with aryl iodides at 90 °C in the presence of CuI as catalyst to afford biaryl disulfides and polysulfides, which could be further converted to aryl thiols through a followed reduction using NaBH4 or PPh3 (Scheme 59) [103]. A wide range of functional groups including methoxy, hydroxy, acyl, carboxy

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• this methodology for the synthesis of 1-arylethylpiperazine-2,6-diones intrigued us to examine them in 6-exo-trig cyclization using TfOH followed by reduction with NaBH4/MeOH to accomplish the synthesis of tetrahydropyrazinoisoquinoline. Surprisingly, the reaction of 7a furnished a mixture of ene

• -diamide 9a and substituted pyrazinone 10a in 90:10 ratio. Generally, the syntheses of these types of units are very limited in the literature [31]. Under controlled experimental conditions, in the absence of NaBH4/MeOH, the ene-diamide 9a was successfully generated in 90% yield using 4 equivalents of TfOH

• the potassium salt of N-benzyliminodiacetic acid in THF at reflux to furnish the expected imides 8a–c, 8h, and 8i in good yields (Scheme 6). The imide 8h was subjected to the cyclization reaction conditions using 6 equivalents of TfOH under neat conditions at 70 °C followed by reduction using NaBH4

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• hydride donors (Scheme 6). Alternatively, secondary amines could involve an elimination of HCN and reduction of the formed imine. NaBH4 [45][46][47][48][49][50][51] or NaBH3CN [47][52][53][54][55][56][57][58][59] are widely used hydride donors and, less frequently, BH3 [60][61], AgBF4/Zn(BH4)2 [62][63][64

• treatment with NaBH4 in 2-propanol by using both basic and nucleophilic properties of the hydride ion. The proposed mechanism involves a double-bond isomerization to the α-aminonitrile intermediate which is then reduced by the hydride ion in a classical way (Scheme 7). Interestingly, deuterium-labelling

• phenanthroquinolizidines (13, n = 2). Anticancer activities of these 18 compounds were evaluated against three human cancer cell lines. BH3·THF containing NaBH4 has been used for the reduction of diimines [72][73] and was studied in-depth by Zhang and co-workers in the reductive decyanation reaction. In their work, the

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

• selective Luche reduction [49][50] of the γ-ketophosphonate 2a using NaBH4 in the presence of CeCl3·6H2O in methanol at 0 °C. The TLC of the reaction mixture and analysis of 1H NMR and 31P NMR spectra showed the exclusive formation of the 1,2-adduct 5 (Scheme 5). The literature survey revealed that γ

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• introduction of the methylseleno moiety was performed by nucleophilic substitution of the α-bromide in 5 with methylselenol obtained by in situ reduction of dimethyl diselenide with NaBH4 [23]. The obtained crude methyl β-selenofucoside was anomerized under Lewis acid catalysis to give the anomeric mixture in

• -methylation in position 2 could solve the phase problem for Lb-Tec2 structure determination. Synthesis of 3 through initial introduction of the seleno aglycon and subsequent O-methylation. Reagents and conditions: (a) NaOAc, Ac2O, 140 °C, 3 h; (b) TMSBr, CH2Cl2, 0 °C–rt, 6 h; (c) Me2Se2, NaBH4, MeCN, 90 °C

• ) PdCl2, CH2Cl2, MeOH, rt, 24 h; (f) NaOAc, Ac2O, 90 °C, 1.5 h; (g) TMSBr, CH2Cl2, 0 °C, 2.5 h; (h) (Me2Se2, NaBH4, MeCN, 90 °C, 1 h), CH2Cl2, 90 °C 15 min–1 h; (i) NaOMe, MeOH, rt, 30 min–2 h; (j) Ac2O, pyridine, 0 °C to rt, 3 h; (k) Ac2O, BF3·OEt2, 0 °C to rt, 17 h; (l) BF3·OEt2, CH2Cl2, rt, 20 h

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• aqueous NaOH followed by NaBH4 reduction of the crude inosose mixture. Although these pioneering results were not of synthetic significance, they elucidated for the first time the biosynthetic correlation between D-glucose and myo-inositol through the intermediate formation of D-xylo-hexos-5-ulose. A more

• anti reduction using NaBH4 as a reducing reagent in an alcoholic solvent (condition A). In particular, it has been proven that the axial OH group β to the keto function plays a fundamental role in directing the nucleophilic attack [45][46][47]. It has also to be mentioned that by changing the