Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• form of the alkaloid, mappicine [64], and indeed it can be converted into the latter by NaBH4 reduction of the ethyl ketone. A brief historical aside: The term “mappicine ketone” was apparently introduced by Kametani [65], who synthesized 36 in the course of investigations directed toward mappicine

Continuous preparation of carbon-nanotube-supported platinum catalysts in a flow reactor directly heated by electric current

• Alicja Schlange,
• Antonio Rodolfo dos Santos,
• Ulrich Kunz and
• Thomas Turek

Beilstein J. Org. Chem. 2011, 7, 1412–1420, doi:10.3762/bjoc.7.165

• salt on carbon support material followed by the reduction with a proper reducing agent (NaBH4, N2H4) or under a gaseous reducing environment (H2), microemulsion method, based on a water–oil system where surfactant molecules are used for stabilization of nanoparticles, and colloidal method, based on

Reductive amination with zinc powder in aqueous media

• Giovanni B. Giovenzana,
• Daniela Imperio,
• Andrea Penoni and
• Giovanni Palmisano

Beilstein J. Org. Chem. 2011, 7, 1095–1099, doi:10.3762/bjoc.7.125

• ], Zn(BH4)2/ZnCl2 [10], NaBH4/Mg(ClO4)2 [11], electrochemistry [12], 1,4-dihydropyridines [13][14], Ti(OiPr)4-PMHS [15], NaBH4-CoCl2 [16], iPrOH/RuCl(PPh3)2 [17], BH3·Me2S [18], PhSiH3-Bu2SnCl2 [19], and Zn/HCOONH4 [20]. Although the choice of reagents for reductive amination is quite large, a closer

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• synthetic scheme comprise the cascade Dibal reduction/transimination/NaBH4 reduction of the enantiomerically pure 94, followed by the RCM step (CH2Cl2, 3.5 mol % 1st-generation Grubbs catalyst, reflux under Ar for 48 h) and Upjohn dihydroxylation to afford the target compounds (Scheme 18 for 96). RCM

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

• Bryan Ringstrand,
• Martin Oltmanns,
• Jeffrey A. Batt,
• Aleksandra Jankowiak,
• Richard P. Denicola and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2011, 7, 386–393, doi:10.3762/bjoc.7.49

• -4-pentylcyclohexyl)acetaldehyde (9) [49]. The aldehyde was reduced with NaBH4 and subsequently brominated with PBr3 to give 1-bromo-2-(trans-4-pentylcyclohexyl)ethane (10) in overall yield of 42% (Scheme 9). Bromide 10 has been reported in the literature, but experimental details are lacking [50][51

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• the glycosidic linkage. For α-mannosylation of primary and secondary alcohols, the mannosyl donors 16 [38] and 17 were used. Treatment of glycosyl bromide 11 with NaBH4/KI in MeCN [39] afforded the crystalline 1,2-O-benzylidene acetal 18 as a single diastereoisomer in quantitative yield (Scheme 3

Achiral bis-imine in combination with CoCl₂: A remarkable effect on enantioselectivity of lipase-mediated acetylation of racemic secondary alcohol

• K. Arunkumar,
• M. Appi Reddy,
• T. Sravan Kumar,
• B. Vijaya Kumar,
• K. B. Chandrasekhar,
• P. Rajender Kumar and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, 1174–1179, doi:10.3762/bjoc.6.134

• -ethyl-N-methylcarbamoyl chloride followed by reduction with NaBH4 (Scheme 3), was selected for our purpose. Subsequently, the enzymatic processes were carried out and the isolated reaction mixture was analysed by chiral HPLC. Initially, the CAL-B mediated acetylation of (RS)-4 was carried out in the

Design and synthesis of a cyclitol-derived scaffold with axial pyridyl appendages and its encapsulation of the silver(I) cation

• Pierre-Marc Léo,
• Christophe Morin and
• Christian Philouze

Beilstein J. Org. Chem. 2010, 6, 1022–1024, doi:10.3762/bjoc.6.115

• then was deblocked (tetrabutylammonium fluoride in THF) to afford 5 (86%). Inversion of configuration was accomplished via Swern oxidation [20] to furnish ketone 6 (95%), which was then reduced (NaBH4, CH3OH) to 7 (99%). Although a configurational assignment did not prove possible from 1H NMR data (in

Systematic investigations on the reduction of 4-aryl-4-oxoesters to 1-aryl-1,4-butanediols with methanolic sodium borohydride

• Subrata Kumar Chaudhuri,
• Manabendra Saha,
• Amit Saha and
• Sanjay Bhar

Beilstein J. Org. Chem. 2010, 6, 748–755, doi:10.3762/bjoc.6.94

• -24146223 10.3762/bjoc.6.94 Abstract 4-Aryl-4-oxoesters undergo facile reduction of both the keto and the ester groups with methanolic NaBH4 at room temperature to yield the corresponding 1-aryl-1,4-butanediols whereas 4-alkyl-4-oxoesters furnish the corresponding 1,4-butanolides via selective reduction of

• the keto moiety. Results of a detailed and systematic investigation of the reaction are described. Keywords: diols; esters; lactones; reduction; Introduction Chemoselective reductions of aldehydes, ketones and imines are generally accomplished using NaBH4 in methanol where other reducible functional

• -lactone) [24]. Following the above noted literature precedences [1][2][17][22][23][24][25][26][27] on the utility of NaBH4, we attempted to reduce 4-aryl-4-oxoesters with methanolic NaBH4 chemoselectively. Surprisingly, we found that 4-aryl-4-oxoesters underwent facile reduction of both the keto and the

Addition of lithiated enol ethers to nitrones and subsequent Lewis acid induced cyclizations to enantiopure 3,6-dihydro-2H-pyrans – an approach to carbohydrate mimetics

• Fabian Pfrengle and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 75, doi:10.3762/bjoc.6.75

• cyclohexylidene-substituted dihydropyran cis-5d afforded α-bromo ketone 17 which, upon treatment with NaBH4, produced epoxypyran 18 (Scheme 8). Epoxide 18 was obtained as a single diastereomer and should be a promising substrate for subsequent nucleophilic addition reactions leading to another series of

• with high structural similarities to carbohydrates. Reduction of the carbonyl group of 8 by NaBH4 followed by hydrogenolysis of the N,O- and N-benzyl-bonds furnished aminopyran 24 (Scheme 12). Similarly, nitrone 21 was smoothly converted to the diastereomeric aminopyran 26 by analogous reductive

• transformations. α-Hydroxyketones 9 and 13 were used as precursors for the preparation of compounds with an additional hydroxyl group, such as aminopyrans 28 and 30 (Scheme 13). Reduction of 9 with NaBH4 in the presence of CeCl3 and subsequent hydrogenolysis furnished compound 28 in excellent yield. The presence

Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring

• Arumugam Kodimuthali,
• Padala Lakshmi Prasunamba and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, No. 71, doi:10.3762/bjoc.6.71

• (OPr)4, NaBH4, 12 h (67% yield); (viii) (Boc)2O, TEA, DCM, 0 °C, 2 h (70% yield); (ix) Pd/C, MeOH, H2, RT, 4 h (85% yield). Reagents and conditions: (i) NaH, LiBr, DMF - DMSO, 12 h (55% yield); (ii) NaH, LiBr, CH3I, DMF - THF, RT, 12 h (65% yield); (iii) NaHCO3, DMSO, 100 °C, 2 h (40% yield); (iv) TFA

Chemical synthesis using enzymatically generated building units for construction of the human milk pentasaccharides sialyllacto-N-tetraose and sialyllacto-N-neotetraose epimer

• Dirk Schmidt and
• Joachim Thiem

Beilstein J. Org. Chem. 2010, 6, No. 18, doi:10.3762/bjoc.6.18

• units in all pentasaccharides for NMR assignment. Preparation of pentasaccharide 8. 1) MeOH, acidic ion exchange resin; 2) Ac2O, pyridine; 3) 80% HOAc, 90 °C; 4) NIS, CF3SO3H, 61%; 5) NiCl2•6H2O, H3BO3, EtOH, then NaBH4, EtOH and acidic workup. Preparation of pentasaccharide 14. 1) MeOH, acidic ion

• exchange resin; 2) Ac2O, pyridine; 3) 80% HOAc, 90 °C; 4) TBDPSCl, imidazole, DMF; 5) NIS, CF3SO3H, 53%; 6) NiCl2•6H2O, H3BO3, EtOH, then NaBH4, EtOH, then acidic workup; 7) CF3CO2H, CH2Cl2. Acknowledgements Support of these studies by the Deutsche Forschungsgemeinschaft (SFB 470, A5) and the Fonds der

Templated versus non-templated synthesis of benzo-21-crown-7 and the influence of substituents on its complexing properties

• Wei Jiang and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2010, 6, No. 14, doi:10.3762/bjoc.6.14

• for 24 h in a mixture of 90 ml of absolute ethanol and 60 ml of CHCl3. After cooling down to room temperature, NaBH4 (1.86 g, 49 mmol) was added and the resulting solution stirred at room temperature for another 24 h. The solvent was removed under vacuum. The resulting residue was treated with water

Recognition properties of receptors consisting of imidazole and indole recognition units towards carbohydrates

• Monika Mazik and
• André Hartmann

Beilstein J. Org. Chem. 2010, 6, No. 9, doi:10.3762/bjoc.6.9

• solution was cooled to 0 °C and NaBH4 (6.80 mmol) was added in portions. The reaction mixture was stirred for 1 h at 0 °C and for additionally 6 h at room temperature. The solvent was removed and the residue was taken up in chloroform/water (100 mL, 1:1). The separated organic phase was further washed with

• -carbaldehyde (19) CH3OH, 3 d; h) 8 equiv of NaBH4, 0 °C to r. t., 12 h (78% of 4, 92% of 5). Solubilization of sugars in CDCl3 by receptor 4 and 5 (1 mM solution). Change in chemical shifta observed during 1H NMR titrations of receptor 4 or 5 with sugar 6a, 7a, 8a or 11 in CDCl3. Association constantsa,b for

Synthesis of (3R,5R)-harzialactone A and its (3R,5S)-isomer

• Gowravaram Sabitha,
• Rangavajjula Srinivas,
• Sukant K. Das and
• Jhillu S. Yadav

Beilstein J. Org. Chem. 2010, 6, No. 8, doi:10.3762/bjoc.6.8

• to obtain 8 in 64% yield. Removal of the dithioketal using HgCl2/CaCO3 in CH3CN/H2O (4:1)[12] provided the corresponding hydroxyketone 4 in 82% yield. Treatment of 5 with NaBH4 and MeOBEt2 [13][14] stereoselectively formed the syn diol 9 in good yield (80%). The diol 9 was subsequently transformed

Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.0^2,6]decane skeleton

• Matthias Breuning,
• Tobias Häuser,
• Christian Mehler,
• Christian Däschlein,
• Carsten Strohmann,
• Andreas Oechsner and
• Holger Braunschweig

Beilstein J. Org. Chem. 2009, 5, No. 81, doi:10.3762/bjoc.5.81

• the racemic ketone rac-9. i) NH4OAc, HOAc, Δ, 4 d, 100%; ii) LiAlH4, THF, Δ, 1 d, 87% [24]; iii) Boc2O, CH2Cl2, rt, 16 h, 85%; iv) NaBH4, Me2SO4, THF, rt, 6 h, then NaOH, H2O2, Δ, 90 min, 75%; v) PCC, Celite®, CH2Cl2, rt, 16 h, 79%. Enantioselective hydrosilylation/oxidation of 11. i) HSiCl3, [Pd(C3H5

• )Cl]2 (0.06 mol %), (R)-MOP (0.25 mol %), toluene, rt, 3 d, then evaporate, then KF, KHCO3, H2O2, THF/MeOH, rt, 1 d, 81%. Initial route to the aldehyde rac-15. i) MePPh3+Br−, t-BuOK, toluene, Δ, 7 h, 77% or Mg, TiCl4, CH2Cl2, 0 °C → rt, 2 h, 55%; ii) NaBH4, Me2SO4, THF, 0 °C → rt, 18 h, then NaOH

Studies on polynuclear furoquinones. Part 1: Synthesis of tri- and tetra- cyclic furoquinones simulating BCD/ABCD ring system of furoquinone diterpenoids

• Faruk H. Shaik and
• Gandhi K. Kar

Beilstein J. Org. Chem. 2009, 5, No. 47, doi:10.3762/bjoc.5.47

• aromatized with DDQ in refluxing benzene, 2-bromo-1-naphthaldehyde (2) was produced in excellent yield. Reduction (NaBH4/EtOH) of the aldehyde 2 produced the alcohol 3 as a colorless solid, in 94% yield, which on reaction with PBr3/CCl4 produced the bromide 4 as a light yellow solid. The bromide was then

• furoquinone 13. Assignment of chemical shifts (1H NMR and 13C NMR) of compound 13. Reagents and conditions: i) DDQ (1.5 equiv), dry benzene, reflux, argon atmosphere, 37 h, 83%. ii) NaBH4, EtOH, room temperature, 2 h, 94%. iii) PBr3, CCl4, 60 °C, 1 h, 82%. iv) KCN, DMF, room temperature, overnight then 1 h at

2-Phenyl- tetrahydropyrimidine- 4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β²-amino acids

• Markus Nahrwold,
• Arvydas Stončius,
• Anna Penner,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2009, 5, No. 43, doi:10.3762/bjoc.5.43

• . Chemoselective reduction of 10 was carried out by reaction with sodium borohydride in the presence of Ni(OAc)2. The “nickel boride” formed as black precipitate serves as a highly active hydrogenation catalyst, whereas an excess of NaBH4 serves as hydrogen source [45][46]. The reaction reaches completion within

• . DIB, I2, CH2Cl2, rt, 4 h, then BF3·Et2O, rt, 1 h; c) Ni(OAc)2·4H2O/NaBH4, MeOH/THF, 0 °C, 10 min; d) Boc2O, DMAP, CH3CN, 16 h, rt. Diastereoselective alkylation of 5. Selective ring opening of the heterocycle 11d and isolation of orthogonally protected β2-homoaspartate 16. a) LiOH/H2O2, THF/H2O, 0 °C

On the functionalization of benzo[e][2,1]thiazine

• Kirill Popov,
• Tatyana Volovnenko and
• Julian Volovenko

Beilstein J. Org. Chem. 2009, 5, No. 42, doi:10.3762/bjoc.5.42

• -carbaldehydes 1 and benzo[e][2,1]thiazine-4-chloro-3-carbonitriles 2. a: NaBH4 (2.5 equiv), MeOH, 2 h, room temp.; b: SOCl2 (4 equiv), benzene, 3 h, 0 °C to room temp.; c: HBr (50%), 5 h, reflux; d: NaOMe/MeOH, 2 h, reflux; e: HS–(CH2)2–OH (1.5 equiv), K2CO3, 1,4-dioxane, TEA, 2 h, reflux. a: LiAlH4 (4 equiv

Structural studies on encapsulation of tetrahedral and octahedral anions by a protonated octaaminocryptand cage

• I. Ravikumar,
• P. S. Lakshminarayanan,
• E. Suresh and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2009, 5, No. 41, doi:10.3762/bjoc.5.41

• to the aldehyde also dissolved in dry methanol. Reduction of the resulting Schiff base was achieved using NaBH4. Both higher temperatures (40–50 °C) and fast addition rates lead to mostly polymeric products in the scaled-up synthesis. In the case of 1, a white precipitate is obtained after addition

Synthesis of phosphonate and phostone analogues of ribose-1-phosphates

• Pitak Nasomjai,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2009, 5, No. 37, doi:10.3762/bjoc.5.37

• -hydroxyl group with Deoxo-fluor™ [6] gave 5-deoxy-5-fluoro-2,3-O-isopropylidene-D-ribonic-γ-lactone (15) in good yield and then subsequent reduction of lactone 15 with NaBH4 resulted in the fully reduced diol 16. Diol 16 has been previously synthesised [7], however this route appears to offer a more

• efficient preparation. In our case, even with limiting NaBH4, mixtures of diol 16 and 5-deoxy-5-fluoro-2,3-ribofuranoside 17 were obtained, however treatment with DIBAL-H at 40 °C [8] gave a clean reaction and 5-fluororibofuranoside 17 was recovered in moderate yield. Finally a Wadsworth-Emmons reaction [4

• ) NaBH4, ethanol, 0 °C, 2 h, 65%; d) DIBAL-H, toluene, 40 °C, 64%; e) CH2[P(O)(OMe)2]2, DCM, 50% aq NaOH, 60%. Synthetic route B. Reagents and conditions: a) acetone, concd H2SO4 (cat.), 4 h, 90%; b) TrCl, pyridine, DMAP, rt, 16 h, 94%; c) CH2[P(O)(OMe)2]2, 50% aq NaOH; DCM, 64%; d) anhyd ZnCl2, DCM, rt

Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity

• Nisachon Khunnawutmanotham,
• Nitirat Chimnoi,
• Arunee Thitithanyanont,
• Patchreenart Saparpakorn,
• Kiattawee Choowongkomon,
• Pornpan Pungpo,
• Supa Hannongbua and
• Supanna Techasakul

Beilstein J. Org. Chem. 2009, 5, No. 36, doi:10.3762/bjoc.5.36

• produce aldehydes 21 in good yields. The reduction of 21 with NaBH4 produced alcohols 22, which were converted to the corresponding chlorides 23 through treatment with thionyl chloride in dichloromethane. The reaction of 23a with thiophenolate, 3-methoxythiophenolate, and 3-fluorothiophenolate in N,N

• PPh3, rt, 1 h; (e) NaBH4, THF, H2O, rt, 0.5 h; (f) SOCl2, CH2Cl2, Et3N, rt; (g) NaH, ArSH, DMF, rt, 1 h; (h) NaH, DMF, 50 °C, 0.5 h then MeI, rt, 0.5 h. Reagents and conditions: (a) POCl3, 150 °C, 6 h, 85%; (b) cyclopropylamine, xylene, 105 °C, 4 h, 99%; (c) SnCl2·2H2O, conc. HCl, CH3COOH, rt, 3 h, 83

Enantiospecific synthesis of [2.2]paracyclophane- 4-thiol and derivatives

• Gareth J. Rowlands and
• Richard J. Seacome

Beilstein J. Org. Chem. 2009, 5, No. 9, doi:10.3762/bjoc.5.9

• -BuLi (2.5M in hexanes; 16.5 mL, 41.25 mmol, 2.2 equiv) dropwise over 30 min to give an orange solution. After 1 h tosyl azide (9.20 g, 46.70 mmol, 2.5 equiv) was added and the reaction warmed to rt over 18 h. NaBH4 (6.45 g, 171 mmol, 9 equiv) and tetra-n-butyl ammonium iodide (6.31 g, 17.1 mmol, 0.9

• equiv) were added and the reaction stirred for a further 24 h at rt whereupon a further portion of NaBH4 (2.80 g, 74.0 mmol, 4.0 equiv) was added. After further stirring at rt for 5 days the reaction was poured into saturated aqueous NH4Cl (250 mL) causing effervescence. The aqueous phase was extracted

Synthesis of 3-(phenylazo)-1,2,4-triazoles by a nucleophilic reaction of primary amines with 5-chloro- 2,3-diphenyltetrazolium salt via mesoionic 2,3-diphenyltetrazolium- 5-aminides

• Shuki Araki,
• Satoshi Hirose,
• Yoshikazu Konishi,
• Masatoshi Nogura and
• Tsunehisa Hirashita

Beilstein J. Org. Chem. 2009, 5, No. 8, doi:10.3762/bjoc.5.8

• examined. In order to synthesize 3-(benzylamino)formazan 5a, the reduction of 4a with reductants such as NaBH4 and DIBAL was attempted. However, the desired formazan 5a was not obtained at all. Then, a nucleophilic substitution of 3-chloroformazan 6 with benzylamine was undertaken. The chlorotetrazolium

• salt 2 was easily converted to 6 with NaBH4 (43% yield) or p-(dimethylamino)aniline (73% yield). The reaction of 6 with benzylamine in ethanol, however, did not give the expected 5a, but triazole 3a was formed in 30% yield. In this reaction, 3a is considered to be formed via initially produced formazan

• Na2SO4, the solvent was removed and the residue (72 mg) was purified by column chromatography on silica gel (eluent: CH2Cl2→MeCN) to give a crude product. Recrystallization from ethanol gave 3a (21 mg, 16%). Reduction of chlorotetrazolium salt 2 1. With NaBH4 To a solution of 2 (176 mg, 0.51 mmol) in

Reduction of arenediazonium salts by tetrakis(dimethylamino)ethylene (TDAE): Efficient formation of products derived from aryl radicals

• Mohan Mahesh,
• John A. Murphy,
• Franck LeStrat and
• Hans Peter Wessel

Beilstein J. Org. Chem. 2009, 5, No. 1, doi:10.3762/bjoc.5.1

• ); (c) TBAF, THF, 25 °C, 1.5 h, 85% (27a), 0.5 h, 97% (27d); (d) PBr3, DCM, 0 °C to 25 °C, 1 h, 99% (28a), 93% (28d); (e) PhSH, NaH, THF, 0 °C to 25 °C, 1 h, then 28, 25 °C, 5 h, 98% (29a), 94% (29d); (f) Cu(acac)2, NaBH4, EtOH, 25 °C, 15 h, 70% (30a), SnCl2·2H2O, MeOH, 65 °C, 4 h, 91% (30d); (g) NOBF4