Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• evaluated (Scheme 1). Results and Discussion Chemistry The unsubstituted DHBER was prepared by treating BER with 2.5 equivalents of NaBH4 in pyridine at room temperature [66][67], and employed in the reaction with α-bromohydrazone 1a chosen as the representative model, to determine the optimal reaction

• mmol), 1 (1.0 mmol), DCM 3.0 mL, 25 °C. Isolated yields in parentheses. Synthesis of hydrazono-THBERs 3a–n. Reaction conditions: DHBER (0.5 mmol), NaBH4 (2.0 mmol), MeOH, 3.0 mL, 25 °C. Isolated yields in parentheses. Reaction conditions optimization. Supporting Information Supporting Information File

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• afforded the α-hydroxy esters 166a,b. Dess–Martin oxidation [79][80] of the latter, followed by hydrolysis of the ester gave keto acids 167a,b. Finally, the reductive amination of 167a,b with 25% aqueous ammonia and NaBH4 afforded the racemic β,β-difluorophenylalanine derivatives 168a,b in 67% yield [81

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• accomplished as illustrated in Scheme 3. Reduction of cyclohexanone 15 with NaBH4 gave cyclohexanol 16 in a ratio of 2:1. The major trans product 16a was purified as a single entity by column chromatography and was isolated in 45% yield. Vinyl ether 17 could be efficiently prepared using the methodology

• conditions: a) NBS, HF·Py, DCM; b) t-BuOK, DCM, 42% in two steps [15]; c) TMSCF3, NaI, THF, reflux, 46%. Synthesis of compound 10. Reagents and conditions: a) NaBH4, MeOH, rt, 45%; b) C4H9OCH=CH2, Pd(TFA)2, BPhen, Et3N, 75 °C, 62% [16]; c) TMSCF3, NaI, THF, reflux, 50%. Synthesis of compounds 11. Reagents

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• free aziridine 5a in 81% yield while maintaining the ee value. The reduction of the carbonyl moiety with either NaBH4 or LiAlH4 produced hydroxy-substituted CF2-functionalized aziridine 5b in excellent yield with exclusive diastereoselectivity [47]. Furthermore, the ring-opening of 4a under acidic

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• containing piperazine), respectively. In the next step, Gx-AAA–SBA-15 was dispersed in an aqueous solution of HAuCl4 and stirred for a short time. The reduction of Au was accomplished using an aqueous solution of NaBH4. The obtained material was then centrifuged and washed with deionized water. The resulting

• solid was dispersed in an aqueous solution of CuCl2⋅3H2O for 10 min. The copper species was reduced with an aqueous solution of NaBH4. The metal–dendron SBA-15 material was filtrated, washed with deionized water, and dried to produce x wt % CuYAu–Gx-AAA–SBA-15 (x wt % = weight percent loading of Cu, Y

• graphene oxide (rGO) with copper and palladium species (Scheme 15) [77]. In this study, graphite oxide (GO) was generated according to the modified Hummer’s method. Copper(II) was anchored on GO via ultrasonication. In the next step, copper ions were reduced by adding NaBH4. The mixture was then heated at

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• , regioselective synthesis of hitherto unknown organyl 1,3-thiaselenol-2-ylmethyl selenides 6a–l in high yields (Scheme 8). The synthesis was based on the generation of sodium 1,3-thiaselenol-2-ylmethylselenolate by the reaction of NaBH4 with compound 4 in methanol followed by nucleophilic substitution reactions

• 1,3-thiaselenol-2-ylmethylselenolate through reduction of the Se–Se bond with NaBH4 followed by nucleophilic substitution with alkyl halides (Scheme 11). Thus, two efficient methods for the preparation of novel 1,3-thiaselenol-2-ylmethylselanyl derivatives 6a–l from selenocyanate 4 and diselenides 8

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• chemoselective carbonyl reduction to obtain the corresponding allylic alcohol derivative 36 was achieved in 92% under Luche reduction conditions employing NaBH4/CeCl3 in MeOH/DCM, resulting in the selective synthesis of the syn-alcohol, as a consequence of the formation of the equatorial alcohol favored by

• and Pauson–Khand multicomponent reactions. Follow-up chemistry on compound 5 taking advantage of the enone chemistry. Reaction conditions. (i) NaBH4 (2 equiv), CeCl3.7H2O (2 equiv), DMC/MeOH 1:1 (20 mL/mmol), 25 °C, 1 h; (ii) m-CPBA (1 equiv), DCM (6.5 mL/mmol), 0 °C, 4 h; (iii) EtMgBr 3 M in Et2O (5

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• , 4) as an organocatalyst and meso-tetraphenylporphyrin (H2TPP, 5) as a photosensitizer followed by in situ reduction with NaBH4, proceeded similarly to the reported results for simple, achiral aldehydes giving the desired diols 6–8 in 31–41% yields with moderate conversion and alcohols 9–11 as

• bubbling under irradiation (green high power LED) for 3 h. The light was turned off and a solution was transferred to a round bottom flask with MeOH (1 mL). The reaction mixture was then cooled to 0 °C before NaBH4 (50 mg, 1.3 mmol) was added. After stirring for 15 min at 0 °C the reaction was diluted with

• high power LED). The light was turned off and the mixture was left for phase separation. The organic layer was transferred to a round bottom flask and mixed with MeOH (1 mL). The reaction mixture was then cooled to 0 °C before NaBH4 (50 mg, 1.3 mmol) was added. After stirring for 15 min at 0 °C the

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• of the hydroxymethyl group to the oxoammonium one favours the reaction. Treatment of 15 with NaBH4 in EtOH caused quantitative reduction of the aldehyde group to the hydroxymethyl one, thus yielding 12a identical to that prepared by the alternative method (see below). To prevent oxidative reactions

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• of the desired β-hydroxy ketone was observed. In our experience, the hydrogenolysis of a 2-isoxazoline having a 5-ester group was troublesome. Thus, the 5-ester group was reduced with NaBH4 to give 5. The hydroxy group was subsequently protected with benzoyl (Scheme 3), which also worked as a

• reduction [4][5][6][7][8][9][10][11] of 7 using Et2BOMe and NaBH4 at −78 °C gave stable ethylboronate 8 in 96% yield. Several ethylboronate compounds have been reported [9][10][11][56][57][58][59][60][61][62]. From 8 to 9, no H2O2 treatment was necessary. Rotary evaporation of 8 with CH3OH at ca. 40 °C

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• N-(1-phenylethyl)aziridine-2-methanols 7 Aziridine alcohols 7 are usually prepared by LiAlH4 reduction of the corresponding esters 5 [22][35][36] although a milder method with a NaBH4 and LiCl mixture was also elaborated [37]. A multistep synthesis of (2S,1'R)-7 employing the aziridine ring closure

• NaBH4/ZnCl2 mixture (chelation controlled) gave the aziridine alcohol 20 as a major product. Reductive opening of the aziridine ring produced the amino alcohol 21 which was transformed into the substituted oxazolidin-2-one 22. Its catalytic hydrogenation effected deoxygenation at the benzylic position

• synthesize N-Boc-norephedrine ((1R,2S)-29) the epimeric aziridine alcohol (2S,1'R,1''R)-28 was needed (Scheme 9) [47]. To this end the aziridine ketone (2S,1'R)-30 prepared from Weinreb amide (2S,1'R)-18 was reduced with a NaBH4/ZnCl2 mixture to give almost enantiomerically pure (>99:1) alcohol (2S,1'R,1''R

Synthesis of 9-O-arylated berberines via copper-catalyzed C_Ar–O coupling reactions

• Qiaoqiao Teng,
• Xinhui Zhu,
• Qianqian Guo,
• Weihua Jiang,
• Jiang Liu and
• Qi Meng

Beilstein J. Org. Chem. 2019, 15, 1575–1580, doi:10.3762/bjoc.15.161

• the ketone structure is the predominant one [20]. To destroy such resonance, the isoquinoline core was thus reduced to tetrahydroisoqinoline 1 by NaBH4 [21]. To our delight, this reduced form of berberrubine smoothly underwent Ullmann-type cross coupling with iodobenzene, leading to the 9-O-Ph product

Introduction of an isoxazoline unit to the β-position of porphyrin via regioselective 1,3-dipolar cycloaddition reaction

• Xiujun Liu,
• Xiang Ma and
• Yaqing Feng

Beilstein J. Org. Chem. 2019, 15, 1434–1440, doi:10.3762/bjoc.15.143

• Vilsmeier reaction was carried out after insertion of Cu2+ into the cavity of TPP. In the presence of concentrated H2SO4 the Cu2+ was removed to give the 2-formyl derivative TPP-CHO. Subsequently, the formyl group was reduced by NaBH4, accompanied with chlorination by SOCl2, to afford the chloromethyl

Reversible end-to-end assembly of selectively functionalized gold nanorods by light-responsive arylazopyrazole–cyclodextrin interaction

• Maximilian Niehues,
• Patricia Tegeder and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2019, 15, 1407–1415, doi:10.3762/bjoc.15.140

• solution was stirred at 25 °C for 10 min. Then, a freshly prepared ice-cold aqueous solution of NaBH4 (600 μL, 0.01 M, prepared by diluting an 0.1 M solution) was added in one portion under vigorous stirring. After 10 min, stirring was slowed down to 200 rpm and continued at 25 °C. The seeds were kept at

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• Information File 1 for full experimental details). Both derivatives 9 and 10 (Scheme 2) yielded α,β-unsaturated esters 12 and 13 after treatment with Martin sulfurane [16]. Reduction of compound 12 using NiCl2/NaBH4 in methanol as solvent yielded derivative 14 with excellent diastereomeric ratio (dr = 1:0.03

• )/(Z) = 1:1]; c) Martin sulfurane, DCM, 0 °C, 10 min, 95%; d) NiCl2, NaBH4, −60 °C to −40 °C, 1 h, 96% (dr = 1:0.03); e) Li, EtOH, NH3, −70 °C, 10 min, 61% (dr = 1:0.4); f) i. O2, methylene blue, light, DCM, −30 °C, 30 h; ii. then O2, cat. TFA, DCM, rt, 2 d, 24%; g) i. O2, methylene blue, light, DCM

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• reducing reagent, the solvent used for the reaction and the reaction temperature. Sodium borohydride (NaBH4) and sodium dithionite (Na2S2O4) are the most studied reducing agents for the reduction of N-substituted pyridinium derivatives. Unlike Na2S2O4 which reduces NAD+ regioselectively to 1,4

• -dihydronicotinamide adenine dinucleotide (NADH), NaBH4 reduces NAD+ to a mixture of the 1,2-, 1,4-, and 1,6-NADH isomers [65][66]. Recent attempts to reduce substituted pyridinium salts using less powerful and more selective sodium cyanoborohydride also failed to produce 1,4-DHP derivatives in good yields [56]. As a

• general observation, one may note that dithionite reduction of pyridinium salts, especially those carrying electron-withdrawing substituents in the 5 and 3 positions of the pyridinium core, offers mainly or even exclusively the 1,4-DHP products. NaBH4 reduction does not demonstrate such a selectivity [67

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• investigated (Scheme 11) [48]. While attempts to access the free alkylidene(aminocyclopropanes) from the corresponding trichloroacetamides proved unsuccessful by hydrolysis (1 M aqueous HCl or KOH, EtOH) or reduction (DIBAL-H or NaBH4), Hyland et al. showed that the treatment of (arylmethylene)cyclopropane 13f

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• become luminescent when exposed to reducing agents such as NaBH4, LiAlH4 or BH3 [13]. Procedures for high yield and selective modification of octavinylsilsesquioxane (OVS) via CM with a variety of substituted styrenes, including the ones bearing highly π-conjugated substituents such as phenyl, 1-naphthyl

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• sequence. Reagents and conditions: a) (CF3CH2O)2P(O)CH2COOMe, KHMDS, 18-crown-6, THF; b) PTSA, MeOH; c) NaOCl, TEMPO, KBr, NaHCO3, water/acetone; d) 3 M HCl, 80 °C. Synthesis of the orthogonally protected (2S,3R)-2 from a chiral aziridine. Reagents and conditions: a) LiHMDS, AcOt-Bu, THF; b) NaBH4, iPrOH

• (2S,3R)-2 via Sharpless epoxidation. Reagents and conditions: a) TBHP, D-(−)-DIPT, Ti(OiPr)4, MS, CH2Cl2; b) t-BuMe2SiCl, imidazole, DMAP, DMF; c) NaIO4, RuO2, AcOEt/H2O. Synthesis of (2S,3S)-2 from the imide 51. Reagents and conditions: a) NaBH4, MeOH/CH2Cl2; b) Ac2O, pyridinium perchlorate; c) furan

• of (2S,3S,4R)-4 and (2R,3S,4R)-4 from cyclic imides 106. Reagents and conditions: a) NaBH4, MeOH; b) Ac2O, pyridine; c) Me3SiCN or Bu3SnCN, BF3·OEt2, toluene or CH2Cl2; d) Ce(NH4)2(NO3)6, MeCN/H2O; e) 6 M HCl, reflux, then Dowex 50W-X8. Synthesis of (2R,3R,4R)-4 and (2S,3R,4R)-4 from the cyclic meso

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• ) Na2CO3, ACN, 80 °C, 24 h, 33%. a) MsCl, Et3N, DMAP, DCM, −78 °C to rt.; b) Na2CO3, KI, ACN, reflux. a) AllBr, TBAB, PhMe, 50% NaOH, 50 °C, 18 h, 94%; b) i. O3, DCM, −78 °C; ii. NaBH4, DCM, MeOH, rt, 16 h; c) MsCl, Et3N, DMAP, DCM, −78 °C to rt, 43% over 3 steps; d) Na2CO3, KI, ACN, 15, reflux. a) 50

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• ) thymine, BSA, NIS, DCM, 0 °C to rt, 4.5 h; ii) Bu3SnH, AIBN, toluene, 90 °C, 30 min, 70%; b) HF-pyridine, DCM/pyridine 5:1, 0 °C to rt, 1.5 h, 71%; c) CeCl3·7H2O, NaBH4, MeOH, 0 °C, 1 h, 92%; d) DMTr-Cl, pyridine, rt, 3 d, 76%; d) CEP-Cl, DIPEA, THF, rt, 4 h, 62%. Synthesis of the cytidine phosphoramidite

• building block 16. Reagents and conditions: a) Ac2O, pyridine, 0 °C to rt, 17 h, 87%; b) N-benzoylcytosine, BSA, TMSOTf, ACN, 0 °C to rt, 3.5 h, 41%; c) HF-pyridine, DCM/pyridine 5:1, 0 °C, 15 min, 91%; d) i) CeCl3·7H2O, NaBH4, MeOH, −78 °C, 20 min; ii) Bz2O, DMF, rt, 7 h, 94%; e) DMTr-OTf, DCM/pyridine 1

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• addition of less than one equivalent of the sodium borohydride as well as the use of tetramethylammonium borohydride or sodium cyanoborohydride, but none were overly successful. Indeed, a representative assay (dry THF, 24 hours at 0 °C, 0.7 equivalents of NaBH4) led to the isolation of 49% of compound 3ae

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