Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• 13in high yield, and most importantly, without a reduction in ee value. To our knowledge, this is the first asymmetric synthesis of 13. On the other hand, NaBH4, previously employed by Belliotti [8] for the reduction of rac-12, gave less satisfactory results. Then 13 was subjected to reaction with

Total synthesis of panicein A₂

• Lili Yeung,
• Lisa I. Pilkington,
• Melissa M. Cadelis,
• Brent R. Copp and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215

• the double bond in the presence of the α,β-unsaturated ketone, including Pd/C and H2, NaBH4 and Pd/C in the presence of acetic acid [9], and NaBH4 with CoCl2 [10]; all of these reductive conditions gave complex, inseparable mixtures of overreduction products of the ketone functionality. We therefore

• decided to selectively reduce the ketone to an alcohol – this would allow for the uncomplicated hydrogenolysis of the olefin. Following this, subsequent oxidation of the alcohol would give the desired ketone 13. The reduction of ketone 12 to alcohol 14 with NaBH4 was complete after a reaction time of 10

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• -iodoaniline, PPTS (pyridinium p-toluenesulfonate) and NaBH4 (64%) was followed by N-acylation of the aniline nitrogen atom (80%) provided the target precursor 10. The reaction of 7 with 1 equiv of tributyltin hydride was incomplete, but the use of 2.5 equiv of tributyltin hydride at fixed concentration ([7

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• , Seeberger and McQuade reported on further improvements of this strategy enabled by the development of a NaBH4-based flow reduction procedure of artemisinin (55) to yield dihydroartemisinin (61) as well as in-line purifications and derivatisations to also generate several related malaria medications (i.e., β

• in 2-Me-THF as a greener solvent [68]. Although this reductant is more expensive than NaBH4 this approach convinces through its simplicity and superior productivity (~1.6 kgh−1L−1). Beside the use of photochemical processing towards the synthesis of artemisinin and its derivatives, this strategy has

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• . Reagents and conditions: a) PhMe, reflux, 19 h, 74%; b) LiBr, NaBH4, THF, MeOH, −10 °C → rt, 20 h, 77%; c) PBr3, THF, 0 °C → rt, 20 h, 75%; d) (i) 13, MeCN, DMF, 80 °C, 15 min, (ii) Hg(OAc)2, CHCl3, AcOH, rt, 24 h, (iii) DDQ, PhCl, reflux, 4 h, 52% (from 12). Preparation of 7. Reagents and conditions: a

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• . Conditions: (a) piperidine, PhCOOH, toluene, reflux 4 h; (b) NaBH4, MeOH/MeCN, rt, 3.5 h; (c) KOH, H2O, reflux, 8 h; (d) H2SO4, H2O, reflux, 20 h; (e) MeOH, SOCl2, reflux, 4 h; (f) Meldum’s acid, HCOOH, Et3N, 100 °C, 4 h. The synthesis of the starting β-enaminones. Conditions: (a) H2SO4, 65 °C, 46 h; (b) 1

Discrete multiporphyrin pseudorotaxane assemblies from di- and tetravalent porphyrin building blocks

• Mirko Lohse,
• Larissa K. S. von Krbek,
• Sebastian Radunz,
• Suresh Moorthy,
• Christoph A. Schalley and
• Stefan Hecht

Beilstein J. Org. Chem. 2015, 11, 748–762, doi:10.3762/bjoc.11.85

• ), BF3·Et2O, DDQ, CHCl3, rt; b) Zn(OAc)2, CHCl3/MeOH, rt; c) dipyrromethane 6, BF3·Et2O, DDQ, CHCl3, rt; d) Zn(OAc)2, CHCl3/MeOH, rt; e) 1. benzylamine, trimethyl orthoformate, rt, 2. NaBH4, THF/MeOH, rt; f) Boc2O, triethylamine, CH2Cl2, rt; g) 1. ethynyltrimethylsilane, CuI, PPh3, Pd(PPh3)4, TEA

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• . NaOAc, Ac2O, 140 °C, 3 h; b. K2CO3, CH3OH, rt, 10 min; (iii) W-1 Raney nickel, acetone, rt, 45 min; (iv) NiCl2·6H2O, NaBH4, MeOH/THF (11:4), 0 °C, 10 min. Proposed reaction sequence for the synthesis of a mixture of carbaldehydes 5a and 5a’ using Raney nickel, Ni////{H}, as a desulfurizing agent. K2CO3

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• of the isosteviol moiety could be reduced to the alcohol with NaBH4–EtOH, thus furnishing a second set of modified amphiphilic organocatalysts. These isosteviol-modified hydroxyamino acid organocatalysts were tested with success in asymmetric aldol reactions, α-aminoxylation reactions and three

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• oxidative cleavage of the vicinal diol unit in the latter to a formyl group (not isolated) followed by its in situ reduction with NaBH4 delivered the hydroxymethyl chain in 17. Hydrogenolytic removal of the two benzyl ether functionalities with Pearlman’s catalyst then afforded the tetrahydroxyindolizidine

• , pyridine, rt, 12 h, 80%. (iv) HCl (2 N), THF, 18 h, 89%. (v) NaIO4, CH3CN/H2O, 5–10 °C, 30 min, (vi) NaBH4, MeOH, 0°C to rt, 30 min, 92% over two steps. (vii) H2, Pd(OH)2/C, MeOH, 3 h, 81%. Reagents and conditions: (i) OsO4, NMO, acetone/water, 6 h, 95%. (ii) NaH, THF, BnBr, Bu4NI, 0 °C to rt, 6 h, 82

• %. (iii) HCl (2 N), THF, 12 h, 80%. (iv) NaIO4, CH3CN/H2O, 5–10 °C, 30 min; (v) NaBH4, MeOH, 0 °C to rt, 30 min, 90% over two steps. (vi) H2/Pd(OH)2-C, MeOH, 6 h, 80% for 23 and 85% for 24. Supporting Information Supporting Information File 350: Experimental details and analytical data of all new

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• performed at an early stage of the synthetic route than on valuable advanced intermediates. Accordingly, the azide reduction with NiCl2/NaBH4 protocol [29] occurred smoothly on the previously described [25] silyl glycoside 4, and after standard N-acetylation furnished acetamide 5 in high yield (Scheme 1

• antibody levels in sera from conjugates 14–17. Each point represents individual mouse sera; horizontal bars indicate geometric mean titers (GMT) of each group with 95% statistical confidence intervals indicated by upper and lower bars. Reagents and conditions: a) NiCl2/NaBH4, MeOH; b) Ac2O, 86% over 2

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• target compounds. However, we found that compounds 5a–c easily underwent 1,4-additions in the presence of nucleophiles or were decomposed under basic conditions. In this respect, DL-dithiothreitol/diisopropylamine (DTT/DIPA), DIBALH and NaBH4/MeOH failed to furnish the desired reduction products

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• was dissolved in 250 µL water containing 20 mM imidazole (pH 8), 5 mM NaCNBH3, 1 mM EDTA and 1 mM cytidine derivative 1. The reaction was carried out at 37 °C. After 2 hours, 25 µL of 50 mM NaBH4 were added, and the reaction mixture was incubated for additional 15 min. Ethanol precipitation yielded

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• structures (right); bottom row: tc-T (Mol A, left, Mol B, right). Conditions: (a) NaBH4, CeCl3·7H2O, MeOH, −78 °C → rt, 1.5 h, 73% (+9% of C6-epimer); (b) TBS-Cl, imidazole, CH2Cl2, rt, 16 h, 79%; (c) Et2Zn in hexane (1 M), CH2I2, CH2Cl2, 0 °C → rt, 16 h, 86%; (d) PivCl, DMAP, pyridine, ClH2C–CH2Cl, 70 °C

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• and protection of 12a to 1,2-oxazine derivative 13. Conditions: a) 1. SnCl4, CH3CN, 4 h, −30 °C → rt; 2. TBSCl, imidazole, THF, 4 h, rt; b) NaBH4, EtOH, 4 h, −40 °C, 72%, dr 81:19; c) L-selectride, THF, 2 h, −10 °C, 73%, only 12a; d) TBSOTf, 2,6-lutidine, THF, 2 h, 0 °C. Synthesis of bicyclic diols 15

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• H2O/EtOH, 60–100 °C, 7 h–10 d; ii. H2, Pd/C or PtO2; iii. (1) 4-methylbenzenethiol, (2) Ni-Ra; iv. (1) MeI, (2) NaBH4; v. (1) MeI, (2) nucleophile. Reagents and reaction conditions: i. H2O, 90 °C, overnight. Reagents and reaction conditions: i. AcOH, H2O, 60 °C, 12 h-5 d; ii. AcOH, H2O, 60 °C, 8 h

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• ]. Due to the presence of an ester group in the prepared drug derivatives, NaBH4 could not be used as reducing agent for the in situ preparation of these gold nanoparticles [32][33]. The ABC- and 3TC-GNPs were then prepared by the so-called “thiol-for-thiol” ligand place exchange (LPE) reaction [34]. The

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• methodology. This method was used to prove indirectly the 6R configuration at the newly created stereogenic center in allylic alcohol 11. The double bond in 11 was cleaved with ozone and the resulting ozonide was reduced with NaBH4; this sequence afforded sucrose vic-diol 14 and (as a byproduct) sucrose

Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives

• Akshay Kumar and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2014, 10, 929–935, doi:10.3762/bjoc.10.91

• component process involving a domino Knoevenagel–Michael sequence was developed. 3,3'-Disubstituted oxindole could be transformed into spirooxindoles by reduction with NaBH4. Oxindole based Michael acceptors. Primary-tertiary diamine organocatalysts. Diamine catalyzed Michael addition of acetone to

First synthesis of meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2014, 10, 808–813, doi:10.3762/bjoc.10.76

• -triphenylporphyrin. The reaction of this porphyrin with 2,5-dimethoxytetrahydrofuran, followed by the reduction of the nitro group in the presence of NiCl2/NaBH4 afforded 5-(3-amino-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin. This triphenylporphyrin underwent a Pictet–Spengler cyclization after the reaction

• -dimethoxytetrahydrofuran in toluene/acetic acid mixture afforded novel 5-(3-nitro-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin (2) in 89% yield. The reduction of nitroporphyrin 2 was initially carried out by using Sn/HCl, SnCl2·2H2O/HCl, and Pd/C–NaBH4 as reducing agents but the reaction was found to be sluggish and

• provided an inseparable mixture of products. Instead, nitroporphyrin 2 was successfully reduced to 5-(3-amino-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin (3) in the presence of nickel boride, generated in situ by the reaction of NiCl2 and NaBH4 in a CH2Cl2/MeOH mixture at 25 °C. Finally, the

Chromatographically separable rotamers of an unhindered amide

• Mario Geffe,
• Lars Andernach,
• Oliver Trapp and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 701–706, doi:10.3762/bjoc.10.63

• differences and geometries for E- and Z-4 and both transition states (TS1 and TS2) in hexane. The dihedral angle of O–C–N–C1 () and the C–N bond length are given for each state (BP-D3/def2-SVP). Synthesis of formamide 4. Reagents and conditions: a) KHMDS, THF, −78 °C; then: NaBH4, MeOH, 63%. b) HCOOEt, reflux

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• hemiacetal with NaIO4 and reduction with NaBH4 gave triol 6b,which was monosilylated with TBDPSCl to give 7b. Conversion of the secondary hydroxy group in 7b to azide 8b according to the Mitsunobu protocol, and deprotection followed by oxidation of the primary hydroxy group gave azido acid 10b. Finally

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• carbamate protected amino acid derivatives 3 (remaining as impurity in the isolated products 2), quantitative benzylation (1→I) was ensured by successive addition of three portions of benzaldehyde/NaBH4 (Quitt´s procedure [61] → two portions) and by maintaining the pH at a value of 10–11. The extractive

• amidation (2→5) due to competitive formation of the corresponding benzyl esters. Depending on the NaBH4 batch the dibenzyl-protected derivatives 4 formed as side products (<10% referred to 2). The residual impurities (BnOH and 4) were separated either through work up (of amide 5a) or chromatographic

• 5e (along with 30% of reisolated starting material), illustrating the tendency of reagent 6 to attack the side chain ester moiety. Synthesis of syn-amino alcohols C Already the NaBH4 reduction (in MeOH at −40/0 °C) of ketones 7a and 7b and subsequent hydrogenolysis of the Cbz-group in one-pot

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• then poured into MeOH/CH2Cl2 (1:4, 5 mL) at 0 °C. To this solution, NaBH4 (5 mmol) was added, and the mixture was stirred at room temperature for 1 h. The reaction was quenched with saturated aqueous NH4Cl, and the mixture was extracted with Et2O. The organic layer was dried over Na2SO4, concentrated