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

• ] (Scheme 2). Furthermore, copper-catalysed reactions or oxidation with sodium hypochlorite were also described to yield the aromatic quinazoline core [26][29][30] (Scheme 2). Besides all the oxidation reactions described, also reductive conditions applying NaBH4 onto the tetrahydroquinazoline-based aminal

• 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

• , 70 °C, 1–3 h. Reagents and conditions: (a) (i) MeNH3Cl, Et3N, DMF, 70 °C, 3 h; (ii) AcOH, 70 °C, 4 h; (iii) n-PrBr, t-BuOK, DMF, 110 °C, 16 h; (iv) LiAlH4, THF, 70 °C, 2–3 h; (b) (v) 1) acetone, MeOH, 80 °C, 5 h; 2) NaBH4, rt, 3 h; (vi) MeNH3Cl, Et3N, EDCI, HOBt, DMF, 70 °C, 8–14 h. Calculated

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• cyclopentanone 3. Reagents and conditions: (a) Al2O3, SiO2, MS 5 Å, DCM, rt, 5 d; (b) cation exchanger Dowex 50WX4, MeOH/H2O 5:1, rt, 3 N HCl (drops), column chromatography. Synthesis of rosaprostol stereoisomers 1a and 1c. Reagents and conditions: (a) KOH/Al2O3, OHC(CH2)5CO2Me, C6H6, 3 h rt; (b) Te, NaBH4, EtOH

• , 6 h, rt; (c) 1 N NaOH, EtOH, 3 h, 45 °C; (d) L-Selectride, THF, −75 °C, 4 h. Conversion of methyl ester (+)-6 into rosaprostol (−)-1a. Reagents and conditions: (a) L-Selectride, THF, −45 °C, 3 h; (b) O2 (air), Pd/C, NaBH4, KOH, H2O/MeOH 2:1. Synthesis of rosaprostol stereoisomers 1b and 1d. Reagents

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

• equiv NaBH4, 1.2 equiv I2, THF, 66 °C, 18 h, 86%; (e) 1 equiv Boc2O, 1.2 equiv triethylamine, CH2Cl2, 0 °C, 3 h, 100%; (f) 1.1 equiv MsCl, 1.1 equiv triethylamine, CH2Cl2, 0 °C, 3 h, 79%; (g) 3 equiv NaN3, DMF, 24 °C, 120 h, 96%; (h) 2 equiv SO3*Py, 2.3 equiv pyridine, 4.1 equiv triethylamine, DMSO

• , CH2Cl2, 0 °C, 10 min, 24 °C, 2 h, 87%; (i) H2, Pd/C, MeOH, overnight, 84%; (k) 1 equiv 17, THF, 48 h, 2 equiv NaBH4; MeOH, 96 h, 58%; (l) 10 equiv TFA, CH2Cl2, 40 °C, 24 h, 100%; (m) 1.3 equiv dimethyl trithiocarbonate, MeNO2, 101 °C, 2 h, 4 equiv AcOH, 2 equiv MeI, 101 °C, 3 h, 67% as iodide salt 10a

Experimental and theoretical insights in the alkene–arene intramolecular π-stacking interaction

• Valeria Corne,
• Ariel M. Sarotti,
• Carmen Ramirez de Arellano,
• Rolando A. Spanevello and
• Alejandra G. Suárez

Beilstein J. Org. Chem. 2016, 12, 1616–1623, doi:10.3762/bjoc.12.158

• chemical transformations under microwave irradiation [17], affording the cycloadducts 3a,b in very good yields (76–81%) after irradiating a THF solution of 1 and 2 at 150 °C during 4 hours. The reduction of the ketone group in 3 with NaBH4 produced alcohols 4 and 5 in excellent yields and a ratio of about

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• synthetic pathway described above was reimplemented starting from tert-butyldiphenylsiloxysqualene 23 readily obtained in 85% yield from squalenaldehyde 10 by NaBH4 reduction followed by protection with tert-butyldiphenylsilyl chloride. Functionalisation of the opposite extremity of the polyisoprenoid chain

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• [56][57], and the resulting aldehydes (not shown) were reduced to the terminal alcohols with NaBH4, giving the desired pyrimidinones 3 and 4. These compounds represent key intermediates which may be transformed into the targeted natural products 1 and 2 following previously established protocols [6

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• oxidative coupling sequence (Scheme 48). Similarly, the tricyclic N-heterocyclic core in natural (+)-asperazine and idiospermuline was also efficiently synthesized in 71% overall yield. The oxindole was reduced to the lactol by NaBH4, which was then subjected to a camphorsulfonic acid (CSA)-promoted

Elucidation of a masked repeating structure of the O-specific polysaccharide of the halotolerant soil bacteria Azospirillum halopraeferens Au4

• Elena N. Sigida,
• Yuliya P. Fedonenko,
• Alexander S. Shashkov,
• Nikolay P. Arbatsky,
• Evelina L. Zdorovenko,
• Svetlana A. Konnova,
• Vladimir V. Ignatov and
• Yuriy A. Knirel

Beilstein J. Org. Chem. 2016, 12, 636–642, doi:10.3762/bjoc.12.62

• with NaBH4, desalted with an Amberlit IR-120 (H+-form) resin and fractionated by exclusion chromatography on TSK HW-40 (S) in 1% AcOH to yield a mixture of oligosaccharide (OS) 1 and OS 2 (7 mg) and a higher molecular mass material. The latter was fractionated by HPLC on a reverse-phase Zorbax C18

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• reduced by NaBH4 at pH 7–8, which was kept constant by the continuous addition of 85% H3PO4 to avoid phenolic acetyl-group cleavage. The p-acetoxybenzyl alcohols 6a–c were isolated in 85–95% yields. p-Hydroxyphenylacetic acid (7) and ferulic acid (10) are also more readily available on the market than the

• carboxylic function with NaBH4–I2 in THF (Scheme 2). Due to the higher lability of the phenolic acetate under basic conditions, the method published by Kanth and Periasamy [32] was slightly modified. For this, the reagents were added at lower temperature, the reaction time was prolonged and a solution of

• protected and deprotected products. Reagents and conditions: a) Ac2O, pyridine, rt, 10 h, >98%; b) NaBH4, H3PO4, −5 °C, 85–95%. Reagents and conditions: a) Ac2O, H2SO4, 5 °C to rt, 30 min, >94%; b) 1. NaBH4, THF, 5 °C, 10 min, 2. I2, 5 °C, 15 min, rt, 3 h, 84% for 9, 69% for 12. General reaction scheme for

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• , diastereoselective reduction of the cross-benzoin products with NaBH4 afforded valuable syn-diol products. Goodman and Johnson disclosed a dynamic kinetic resolution of β-halo-α-ketoesters via NHC-catalysed asymmetric cross-benzoin reaction. Here, the cross-benzoin reaction of aromatic aldehydes with β-stereogenic-α

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• candidates for PET imaging experiments. Their potential use as radiotracers is under current investigation. Structures of targeted synthetic inositol derivatives. nOe correlations for C-alkenylated inositol intermediates. Synthesis of O-alkylated inositol derivatives 1. Reagents and conditions: a) NaBH4

Hydroquinone–pyrrole dyads with varied linkers

• Hao Huang,
• Christoffer Karlsson,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 89–96, doi:10.3762/bjoc.12.10

• also investigated (vide infra), but did not produce satisfactory results. Settambolo et al. [20] reported a synthetic route starting from an acylation of pyrrole by phenylacetyl chloride via a Friedel–Crafts reaction, followed by reduction by NaBH4, and elimination to give the vinylpyrrole product

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• –Smith method [13] as illustrated in Scheme 3. For further elaboration, aldehyde 15 was reduced with NaBH4 in good yield to generate the corresponding benzyl alcohol 19 [14]. Iodination of 19 to generate 20 with HI in chloroform [15] proved superior (95% yield) to the more classical Appel protocol which

• steps. iii. Zn, CH2I2, TiCl4, THF, 0 °C to 20 °C, 12 h; 79%. Reactions from aldehyde 15: i. NaBH4, THF, 20 °C, 1 h, 98%.; ii. HI (57%), CHCl3, 30 h, 95%; iii. Bu4NN3, acetone/H2O (4:1), 20 °C, 3 h, 94%; iv. MsCl, Et3N, DCM, −78 °C to 20 °C, 85%. Reactions of benzyl azide 21; i. 24, Cu(OAc)2, Na

• ascorbate, t-BuOH, H2O, 20 °C, 16 h, 72%; ii. HCl (6 M), 1,4-dioxane, 80 °C, 48 h, 96%; iii. Ph3P, THF/H2O (10:1), then HCl, rt, 1 h, 74%. Reactions of aldehyde 14: i. NaBH4, THF, rt, 1 h, 98%.; ii. HI (57%), CHCl3, 30 h, 94%; iii. Bu4NN3, acetone/H2O (4:1), rt, 3 h, 91%; iv. 24, Cu(OAc)2, Na ascorbate, t

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• screened and the results are presented in Table 1. Following a procedure reported in the literature [14], the reduction of 4 was carried out with NaBH4 in THF at 25 °C for 1 h (Table 1, entry 1). However, the main product was proven to be the denaphthalenyloxy compound 5’’ by 1H NMR and MS while the

• after reduction, the basicity resulting from NaBH4 might lead to the denaphthalenyloxylation. Therefore, AcOH was used as an additive in the reaction. The results showed that the denaphthalenyloxylation was almost negligible, but the diastereoselectivity was not good enough (Table 1, entry 5). Although

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