From porphyrin benzylphosphoramidate conjugates to the catalytic hydrogenation of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin

• Marcos C. de Souza,
• Leandro F. Pedrosa,
• Géssica S. Cazagrande,
• Vitor F. Ferreira,
• Maria G. P. M. S. Neves and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2014, 10, 628–633, doi:10.3762/bjoc.10.54

• substitution was promoted by microwave irradiation in N-methyl-2-pyrrolidinone. Attempts to remove the benzyl groups of the phosphoramidate moiety by hydrogenolysis with 10% Pd/C led to the cleavage of the P–N bond and the reduction of the macrocycle to hydroporphyrin-type derivatives. The extent of the effect

• of the catalytic hydrogenation to TPPF20 with 10% Pd/C was then studied with a variety of solvents. The results showed that ethanol/DMF is the solvent of choice to produce chlorin TPCF20 and an ethanol/DMF/NEt3 mixture is more adequate to produce isobacteriochlorin (TPIF20). Keywords: catalytic

• [5][6]. This undesired result pointed to the synthesis of a phosphoramidate derivative different from the diisopropyl one. Here, we describe the synthesis of the analogue porphyrin dibenzylphosphoramidates 1a–c. Attempts to remove the benzyl groups by mild hydrogenolysis over 10% Pd/C led to the

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

• phenylglycine derived carbamate 7c. Indeed, if the excess of Selectride was quenched with acetaldehyde after reduction of 7a, the oxazolidine 10a was obtained (under the basic reaction conditions) as the major product. The outcome of the Cbz-cleavage strongly depended on the activity of the commercial Pd/C

• . However, Pd/C freshly prepared from Pd(OAc)2 and activated charcoal according to Felpin [77] delivered consistent results (reaction time < 3 h). Although the Cbz-cleavage beside a benzyl moiety in alcohols as solvent is known (for selected examples of the chemoselective Cbz-cleavage of Bn, Cbz-protected

• . Straightforward, mesylation of hydroxyketone 7a and subsequent Cbz-cleavage (H2, Pd/C) in the presence of HCl delivered the hydrochloride salt 15a, which was easily isolated through filtration and solvent evaporation (Scheme 7). To our delight, subsequent liberation of the free amine through DBU at low

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• phosphorochloridate), 80% over two steps, Scheme 1). N,N-Dimethylisoleucine (10), obtained by reductive dimethylation of isoleucine with aqueous formaldehyde and H2 on Pd/C [10][11], was appended at the N-terminus (DEPC, diethyl phosphorocyanidate) affording tripeptide tert-butyl ester 11. Treatment with TFA

• equiv), pyridine·SO3 (5 equiv), 0 °C, 1 h, 91%. b) LDA (2.5 equiv), t-BuOAc (1.3 equiv), THF, −78 °C, 1 h; separation of diastereomers, (3R,4S)-6: 47%. c) 1,8-bis(dimethylamino)naphthalene (2.5 equiv), Me3OBF4 (2.6 equiv), 4 Å MS, 1,2-DCE, 0 °C, 2 h, rt, 16 h, 87%. d) H2, Pd/C (5%), MeOH, rt, 1 h. e) 8

• (3 equiv), NEt3 (4 equiv), DEPCl (2 equiv), DCM, 0 °C, 2 h, rt, 16 h, 80% from 7. f) H2, Pd/C (5%), MeOH, rt, 90 min. g) 10 (3 equiv), NEt3 (4 equiv), DEPC (1.5 equiv), DCM, 0 °C, 2 h, rt, 16 h, 83% from 9. h) TFA, DCM, 0 °C, 90 min, quant. i) 13 (1 equiv), NEt3 (6 equiv), DEPC (1.3 equiv), DCM, 0 °C

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• (=C-H), 2855–2995 (C-H), 2095 (N3), 1710 (C=O), 1495 (C=C), 1295, 1255 (C-O), 1190–1075 (C-O-C) cm−1; ESI–TOF (m/z): [M + H]+ calcd for C23H37N4O4Si, 461.2579; found, 461.2607. Typical procedure for hydrogenolysis with Pd/C in AcOH/MeOH (procedure 5) (2S,3S,4R,5S,6S)-4-Amino-2,6-bis(hydroxymethyl)-7,7

• -dimethyloxepan-3,5-diol (26): Bicyclic compound 14 (100 mg, 0.309 mmol) was dissolved in dry MeOH (10 mL) and AcOH (2 mL). After addition of Pd/C (100 mg, 0.094 mmol Pd) the suspension was saturated with hydrogen at rt for 1 h followed by stirring under hydrogen pressure (balloon). After reaction completion 18 h

• bicyclic and tricyclic 1,2-oxazines 14, 15 and 20 to aminooxepanes 26, 27 and 28. Conditions: a) H2, Pd/C, MeOH, rt, 18 h. Hydrogenolyses of bicyclic 1,2-oxazines to aminooxepanes 26, 31 and 32 and to diaminooxepane 33 under optimized conditions. Conditions: a) 1. H2, Pd/C, MeOH/AcOH = 5:1, rt, 17 h; 2

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• . afterwards 9 was taken up in 96% ethanol (5 mL/mmol), treated with 10% Pd/C (130 mg/mmol) and hydrogenated at 1 atm and room temperature for 20–40 h (until the reaction was complete (tlc control)). After filtration of the catalyst and evaporation of the solvent, the crude was taken up in dry THF (5 mL/mmol

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• /NEt3, toluene, 1 h at −78 °C, then gradual warming to 65 °C within 6 h and stirred for 43 h at 65 °C, 78% yield, dr = 1.3:1 (78:79). Synthesis of fully functionalized A ring 87. Reagents and conditions: a) HO(CH2)2OH, THF, Pd/C, H2, pH 5, rt, overnight, 97%, de = 100%; b) LDA, TMSCl, THF, −78 °C to rt

Continuous-flow Heck synthesis of 4-methoxybiphenyl and methyl 4-methoxycinnamate in supercritical carbon dioxide expanded solvent solutions

• Phei Li Lau,
• Ray W. K. Allen and
• Peter Styring

Beilstein J. Org. Chem. 2013, 9, 2886–2897, doi:10.3762/bjoc.9.325

• can be formed under kinetic control. The third possibility is the geminal or branched (b) isomer which is usually formed where a cationic intermediate forms that facilitates migration of the σ-Pd–C bond from the terminal alkenic 1-position to the 2-position. In the majority of publications, the

Modulating NHC catalysis with fluorine

• Yannick P. Rey and
• Ryan Gilmour

Beilstein J. Org. Chem. 2013, 9, 2812–2820, doi:10.3762/bjoc.9.316

• . Synthesis of the monofluorinated pre-catalyst 8 (Scheme 2) commenced with an Appel reaction of alcohol 15 to prepare the primary bromide 18. Owing to the potentially labile nature of the primary bromide, this material was used without further purification in the next step. Reduction (H2, Pd/C) furnished the

3-Pyridinols and 5-pyrimidinols: Tailor-made for use in synergistic radical-trapping co-antioxidant systems

• Luca Valgimigli,
• Daniele Bartolomei,
• Riccardo Amorati,
• Evan Haidasz,
• Jason J. Hanthorn,
• Susheel J. Nara,
• Johan Brinkhorst and
• Derek A. Pratt

Beilstein J. Org. Chem. 2013, 9, 2781–2792, doi:10.3762/bjoc.9.313

• % Pd/C and the resulting black suspension was stirred at room temperature under an atmosphere of H2 (1 atm) overnight. The catalyst was removed by filtration through a pad of celite and the filtrate was concentrated under reduced pressure. The crude residue obtained was subjected to flash

• -dimethyl-1H-pyrrol-1-yl)-4,6-dimethylpyrimidine (8). A solution of 5-benzyloxy-2-(2,5-dimethyl-1H-pyrrol-1-yl)-4,6-dimethylpyrimidine [41] in MeOH was treated with 10% Pd/C and the resulting black suspension was stirred at room temperature under an atmosphere of H2 (1 atm) overnight. The catalyst was

Synthesis of indole-based propellane derivatives via Weiss–Cook condensation, Fischer indole cyclization, and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Arti Tiwari

Beilstein J. Org. Chem. 2013, 9, 2709–2714, doi:10.3762/bjoc.9.307

• generation catalyst in dry CH2Cl2 to furnish the desired RCM product 9 in 94% yield. The unsaturated propellane derivative 9 was subjected to hydrogenation in the presence of 10% Pd/C in dry EtOAc under H2 atmosphere to afford the saturated propellane derivative 4 in 95% yield (Scheme 3). Along similar lines

• solution of propellane 9 (50 mg, 0.12 mmol) in dry EtOAc (10 mL), 10% Pd/C (10 mg, 0.09 mmol) was added and the reaction mixture was stirred at room temperature under H2 atmosphere (1 atm) for 28 h. At the end of the reaction (TLC monitoring), the reaction mixture was filtered through a pad of celite and

New syntheses of 5,6- and 7,8-diaminoquinolines

• Maroš Bella and
• Viktor Milata

Beilstein J. Org. Chem. 2013, 9, 2669–2674, doi:10.3762/bjoc.9.302

• % Pd/C (0.40 g) was added to a solution of 4-chlorodiaminoquinoline 4 (0.64 g, 3.3 mmol) in methanol (35 mL) and the resulting mixture was stirred under H2 atmosphere (balloon) overnight at room temperature. Once the reaction was complete, the catalyst was removed by filtration and the dark red

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• , reaction a). Fortunately, 5-epimer 14 (2,5-trans) was diastereoselectively generated through a 10% Pd/C-catalyzed hydrogenation using 4 atmospheres of hydrogen during three days at 25 °C (Scheme 7, reaction b). This trans- arrangement in molecule 14 is not very easy to built because several steps were

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• presence of sodium ethoxide delivers epoxide 1.87. The material is next subjected to hydrogenolysis using Pd/C in methanol with a 1 bar hydrogen pressure to reductively ring open the epoxide. Finally, the transformation of the alcohol to the mesylate 1.88 occurs under standard conditions. In order to

Synthesis of axially chiral gold complexes and their applications in asymmetric catalyses

• Yin-wei Sun,
• Qin Xu and
• Min Shi

Beilstein J. Org. Chem. 2013, 9, 2224–2232, doi:10.3762/bjoc.9.261

• desired compound (S)-8 in 57% yield [49]. Reduction of (S)-8 by using Pd/C and H2 in MeOH produced the desired compound (S)-9 in 95% yield. The preparation of chiral benzimidazolium salt (S)-13 is shown in Scheme 2. Based on our previous work [52], the coupling reaction between compound (S)-9 and 1-bromo

• -2-nitrobenzene was carried out by using Pd2(dba)3 as the catalyst in the presence of bis[2-(diphenylphosphino)phenyl] ether (DPEphos) and Cs2CO3, affording the desired compound (S)-10 in 94% yield [51]. Reduction of (S)-10 was performed under H2 (1.0 atm) atmosphere by using Pd/C as a catalyst

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• employing THF/Pd-C/H2 and examine PEA imine reduction [47][51]. Except for Harada’s work [51], which will be discussed shortly, researchers have not offered experimental evidence to corroborate their in situ cis-to-trans imine isomerization hypotheses, they were consequently speculative [40][47]. Instead

• their reduction with Pd-C/H2 in THF. For the PPA imine of phenyl ethyl ketone they stated that different ratios of the cis/trans-imine could be isolated. Unfortunately, they did not describe how to obtain the different cis/trans-imine ratios, other than to state that they change upon sitting after

• ratio of the imines. This was true regardless of whether the hydrogenation catalyst (Pd, Pt, Raney-Ni) was pre-activated with H2 or not (for further details, see Supporting Information File 1). (Note: The reduction of a small number of cyclic imines with Pd/C has been reported, and showed a significant

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• the reaction speed of the cyclization. A 5-exo-dig product was not observed, presumably as a result of electronic strain. The reaction was completed in 2 hours at 40 °C to afford 3 in good yield (78%). Reduction and deprotection of 3 by means of H2 (1 atm) in the presence of Pd/C for 48 h afforded

• compound was also tested. In this case, the cyclization occurred in similar conditions as described for the N-Boc-protected compound and resulted in a good yield (81%). Yet, under the catalytic hydrogenolytic conditions as described above (H2, 1 atm, 10% Pd/C, rt, 48 h) only deprotection of the nitrogen

• occured, while the desired benzyl ether cleavage and pyridine reduction were unsuccessful. Increase of the pressure to 5 atm or replacement of Pd/C with Pd(OH)2 (Pearlman’s catalyst) did also not result in the obtainment of the desired product. The natural product (−)-epimyritine was thus obtained over 6

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• to rt, 42% 9. NMO = N-methylmorpholine N-oxide. Conversion of 4 to 1. a) 20 mol % Co(acac)2, PhSiH3, 1 atm O2, THF, 0°C, 82%, diastereomeric ratio = 2.4:1; b) Ph3P=CH2, THF, rt; c) 2 mol % Yb(OTf)3, CH2Cl2, rt, 80% (2 steps); d) 1 atm H2, 10% Pd/C, MeOH, rt, 98%. acac = acetylacetonate, Tf

Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe

• Matthew B. Plutschack,
• D. Tyler McQuade,
• Giulio Valenti and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 2022–2027, doi:10.3762/bjoc.9.238

• available from Thales). With a flow rate of 1 mL/min at 100 bar and 70 °C using a 10% Pd/C CatCart, a throughput of 8 mg/min was achieved. The crude reaction solution was pure by NMR and was used without further purification. As shown in Table 1, the hydrogenolysis represents a bottleneck in the synthesis

• , Amberlite IR-120 H+ (100 mL), 0 °C, water, 4 h. b) NH2OH·HCl, NaOAc, MeOH, rt, 6 h. c) H2, Pd/C (10%), 4.4% formic acid, MeOH, rt, 10 h. The initial polymer-supported nitrite set up. A solution of glucosamine hydrochloride was passed over the resin into a round bottom flask and then stirred with heating

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

• David Benito-Alifonso,
• Rachel A. Jones,
• Anh-Tuan Tran,
• Hannah Woodward,
• Nichola Smith and
• M. Carmen Galan

Beilstein J. Org. Chem. 2013, 9, 1867–1872, doi:10.3762/bjoc.9.218

• susceptible to reduction, such as azides. After aqueous workup, the crude materials were subjected to removal of the acetyl groups using sodium hydroxide in methanol (pH = 11) followed by concomitant acetal hydrolysis and azide reduction using hydrogen and palladium on charcoal (Pd/C) in methanolic HCl (5

• sialylated 22b, as the ester groups were removed by reaction with sodium methoxide in methanol followed by saponification of the methyl ester with LiOH at room temperature and subsequent azide reduction catalysed by hydrogen and Pd/C in water to give target 6 in 80% overall yield (Scheme 2). The presence of

• the α-sialyl linkage in 6 was also unambiguously confirmed by the NMR data (H-3eq’ δ = 2.25 ppm, Δδ [H-9’a–H-9’b] = 0.36 ppm) [24]. Then, carbohydrate antigen 1 was obtained also by catalytic hydrogenolysis with Pd/C in methanolic HCl of 18 to yield the amine-containing derivative in 98% yield. To

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• of the reaction mixtures yellowish solids 5 were obtained in good yields. Moreover, the N-nitroso moiety can be easily removed by heating of compounds 4 with NH2NH2·H2O in ethanol in the presence of 10% Pd/C (Table 1, entries 2 and 12) under reflux. We became deeply intrigued by the result obtained

Straightforward synthesis of a tetrasaccharide repeating unit corresponding to the O-antigen of Escherichia coli O16

• Manas Jana and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 1757–1762, doi:10.3762/bjoc.9.203

• transfer hydrogenation with triethylsilane and 10% Pd/C [20]; (b) an acetylation using acetic anhydride and pyridine, and (c) a saponification reaction with sodium methoxide to furnish compound 1, which was purified over a Sephadex® LH-20 gel to give the pure compound 1 in 64% overall yield. The structure

• solution of compound 9 (1 g, 0.69 mmol) in CH3OH/AcOH (10 mL, 20:1, v/v), were added 10% Pd/C (100 mg) and Et3SiH (2 mL, 12.5 mmol), and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was filtered through a bed of Celite®, washed with warm CH3OH, and concentrated under

• synthetic intermediates. Reagents: (a) N-iodosuccinimide (NIS), TfOH, CH2Cl2, MS 4 Å, −30 °C, 1 h, then 0 °C, 1 h, 76%; (b) NIS, TfOH, CH2Cl2/Et2O (1:3, v/v), MS 4 Å, −40 °C, 1 h, 73%; (c) 0.1 M CH3ONa, CH3OH, room temperature, 2 h, 94%; (d) NIS, TfOH, CH2Cl2, MS 4 Å, −20 °C, 1 h, 72%; (e) Et3SiH, 10% Pd/C

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• , CF3CO2H, −78 °C, dr >95:5; (b) Zn, 6 M HCl, EtOAc/EtOH, rt, single diastereoisomer; (c) CSCl2, aq NaHCO3 CH2Cl2/ MeOH, rt. (a) (COCl)2, DMF, CH2Cl2, rt; (b) 21, Py, DMAP, CH2Cl2, rt; (c) EDC, HOBt, THF/CH2Cl2, rt; (d) H2 (1 atm), Pd/C, MeOH, rt; (e) CAN, MeCN/H2O, 0 °C; (f) 4 M HCl in dioxane, MeCN/Et2O

The preparation of several 1,2,3,4,5-functionalized cyclopentane derivatives

• André S. Kelch,
• Peter G. Jones,
• Ina Dix and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 1705–1712, doi:10.3762/bjoc.9.195

•  5). Finally, the hydrogenation of 28 over Pd/C in methanol furnished a mixture of the saturated pentaesters 26 and 27 (ratio 4:1, capillary GC–MS-analysis) in practically quantitative yield (98%). Although we were unable to separate the two components quantitatively by column chromatography on

Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst

• Cybille Rossy,
• Eric Fouquet and
• François-Xavier Felpin

Beilstein J. Org. Chem. 2013, 9, 1426–1431, doi:10.3762/bjoc.9.160

• , activated-charcoal-supported palladium catalyst for hydrogenation and debenzylation [33]. This homemade Pd/C catalyst was prepared by impregnation of activated charcoal by the reduction of Pd(OAc)2 in MeOH under an atmosphere of H2 (1 atm). With these previous results in mind, we reasoned that the

• reported the preparation of indoles in a Pd/C-catalysed reaction in water with CuI as co-catalyst, Ph3P as ligand and 2-aminoethanol as base. To our great pleasure, the application of these conditions with our Pd–Cu/C catalyst, for the coupling of iodoaniline 1 with phenylacetylene (2) provided the

Short synthesis of the common trisaccharide core of kankanose and kankanoside isolated from Cistanche tubulosa

• Goutam Guchhait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 705–709, doi:10.3762/bjoc.9.80

• = 7.5 Hz, H-1A in the 1H NMR and at δ 101.9 (PhCH), 101.3 (C-1A), 97.4 (C-1B) in the 13C NMR spectra]. Removal of the benzylidene acetal group under neutral conditions by using triethylsilane and Pd/C [15] resulted in the formation of disaccharide diol 7 in 80% yield. NOBF4 catalyzed regio- and

• , 6.35. 2-Phenylethyl (2,3,4-tri-O-acetyl-α-L-rhamnopyranosyl)-(1→3)-2-O-acetyl-β-D-glucopyranoside (7): To a stirred solution of compound 6 (4.0 g, 5.82 mmol) and 10% Pd/C (0.5 g) in CH3OH/CH2Cl2 (15 mL, 1:1, v/v) was added Et3SiH (2.8 mL, 17.53 mmol) dropwise, and the reaction mixture was stirred for

• , CH3OH, room temperature, 3 h, 98% for compound 5, 94% for compound 1; (b) PhCH(OCH3)2, I2, CH3CN, room temperature, 1.5 h, 86%; (c) NOBF4, CH2Cl2, −20 °C, 20 min; (d) acetic anhydride, room temperature, 1 h, 76% in two steps; (e) Et3SiH, 10% Pd/C, CH3OH/CH2Cl2 (1:1, v/v), room temperature, 30 min, 80