Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• esters. This started with a study of its condensation with various arylacetals to give ethyl 3-aryl-2-nitroacrylates followed by a reduction (NaBH4 and then zinc/HCl) into α-amino esters. The scope of this method was explored as well as an alternative with arylacylals instead. We also focused on various

• conditions could be detrimental to the stability of some of these α-nitro acrylates. In the past, such reductions have been achieved under fairly uncommon conditions (NaBH4 in a mixture of isopropanol and chloroform over a large proportion of silica gel) [11][12]. However, when tried, no real overall

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions

• Miriam Schehr,
• Daniel Hugenbusch,
• Tobias Moje,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2018, 14, 2799–2804, doi:10.3762/bjoc.14.257

• conditions: i) MeCN, AIBN, NBS; ii) NaBH4, THF; #commercially available iii) BH3·THF complex, THF, *product 17 is not stable; iv) 1. Zinc powder, ammonium chloride, ethanol, 2. Fe(III)Cl3 hexahydrate, H2O/ethanol, acetic acid. Comparison of previous diazocine syntheses approaches compared to the present

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

• Pavel Yanev and
• Plamen Angelov

Beilstein J. Org. Chem. 2018, 14, 2602–2606, doi:10.3762/bjoc.14.238

• comparison of selected peak areas, the partial overlap and broadening of other signals prevented a full and unequivocal assignment. To circumvent this issue, we chose to lock the chain form by reducing the keto group in 11 with NaBH4 (Scheme 7). The alcohols 12 obtained in this way gave clean and well

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

• reported by many researchers [67][68][69]. 3-1. Methyl transfer to thiols Chemical reductants such as NaBH4 or electrochemical reduction could provide Co(I) species, so that α-methylated and β-methylated B12 could be formed by the oxidative addition reaction with a methyl donor. The supernucleophile Co(I

• (III) form of 1 has recently been found to catalyze atom transfer radical addition of alkyl halides to olefins (phenyl vinyl sulfone and acrylates) in the presence of NaBH4 [115]. In addition, a new light-driven method for generating acyl radicals from 2-S-pyridyl thioesters was developed through the

A novel and practical asymmetric synthesis of eptazocine hydrobromide

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan,
• Kuaile Lin and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• reaction, a second strategy was proposed as illustrated in Scheme 4. Tetralone 4 was converted to dihydronaphthalene 11 by reduction with NaBH4 in methanol, followed by dehydration with POCl3/pyridine at reflux (85% yield). In order to get ketone 12, a series of oxidation conditions was tested (Table 2

• improved the reaction yield (Table 3, entries 4 and 5). The reductive methylation of 14 under Eschweiler–Clarke conditions (HCOOH/formalin/reflux) furnished 15 in quantitative yield. The latter was reduced by NaBH4 in methanol at room temperature, and then dehydration and hydrogenation with H2/Pd/C in

• , 54.37, 48.86, 36.18, 26.52, 26.06, 25.82; MS (ES+) m/z: 252.13 [M + Na]+. Preparation of (S)-1-methyl-1-cyanomethyl-7-methoxy-1,4-dihydronaphthalene (11) To a solution of 4 (20 g, 0.087 mol) in MeOH (200 mL) was added NaBH4 (1.98 g, 0.053 mol) in portions at 0 °C. The mixture was stirred at 0 °C for 20

Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• solid was formed (30 min). The solution was allowed to cool down at room temperature and dry MeOH (4.0 mL) was added. The mixture was kept under stirring for 2 h and then cooled at 0 °C. NaBH4 (1.12 g, 11.0 mmol) was added and the mixture was kept under stirring at 0 °C for 15 min and then allowed to

• formation of the two atropoisomeric pseudo[2]rotaxanes 3+1cone and 3+11,2,3-alt. Synthesis of threads 2+ and 3+. Reagents and conditions: a) hexamethyldisilazane, LiClO4, 30 min, 60 °C; b) CH3OH, NaBH4, 2 h, 25 °C; c) TFPBNa, dry MeOH, 25 °C, 18 h. Supporting Information Supporting Information File 408: VT

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• and treated with NaBH4, protected by di-tert-butyl pyrocarbonate to get compound 3. The esterification reaction was carried out subsequently between hydroxy compound 3 and allylacetic acid to afford compound 4, which was further reacted with CF3COOH and followed by the anion exchange in the methyl

• +, 894.6808; found, 894.6813. Compound 3: A mixture of 1 (3.0 g, 10.63 mmol) and 2 (4.0 g, 12.75 mmol) in methyl alcohol (100 mL) was refluxed overnight under a nitrogen atmosphere. After the reaction mixture was cooled to room temperature, NaBH4 (1.6 g, 30.5 mmol) was then added to the solution in portions

Cobalt-catalyzed nucleophilic addition of the allylic C(sp³)–H bond of simple alkenes to ketones

• Tsuyoshi Mita,
• Masashi Uchiyama,
• Kenichi Michigami and
• Yoshihiro Sato

Beilstein J. Org. Chem. 2018, 14, 2012–2017, doi:10.3762/bjoc.14.176

• mixture. The approximate yield of 3 was determined at this stage using 1,1,2,2-tetrachloroethane (δ = 6.1 ppm in CDCl3, 2H) as an internal standard. If the ketone remained, NaBH4 was added to convert it into the corresponding alcohol, which could be easily separated from 3 by silica-gel column

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• the natural product stepharine (3) by reaction with PIDA (15) in trifluoroethanol (TFE) followed by the reduction with NaBH4. The synthesis of the natural product stepharine (3) was obtained in 90% yield by starting from phenolic substrate 116 (Scheme 42). In 2008, Kita and co-workers [117] developed

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• diarylmethyl alcohols with hydride sources. These reactions require a preliminary C–OH bond activation by Brønsted or Lewis acids. Several reagent systems have recently been employed to achieve this goal, including: NaBH4–CF3COOH [26], ZnI2–NaBH3CN [27], HI–Pred [28], H3PO2–I2 [29][30], Mo(CO)6-Lawesson’s

• hydride donors, such as NaBH4 and LiAlH4 in various combinations with ZnI2 and AlCl3 failed [61][62][63]. For instance, the reaction with NaBH4 itself and NaBH4/ZnI2/THF at room temperature and reflux only recovered the substrates. The same result was obtained at room temperature with NaBH4/AlCl3/THF

• , while at reflux the whole substrate was consumed and three unidentified products were formed lacking the SCHS and ArCH2Ar characteristic signals in 1H NMR spectra. With NaBH4/CF3COOH/rt, the substrate underwent decomposition. In our case, the use of the Lau’s procedure in DCE for the reductive

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

• toward alcohols of 61+.BF4− in the auto-recycling process was also reported. However, to test the reactivity, the reactions of 61+.BF4− with a nucleophile such as NaBH4, diethylamine, and methanol were carried out to afford 7-adducts 64–66. Compound 64 was oxidized by DDQ to regenerate 61+.BF4− in good

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