Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

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

• derivatives 15a and 15b. Conditions: a) H2, Pd/C, MeOH, EtOAc, 20 h, rt; b) H2, Pd/C, iPrOH, EtOAc, NEt3, 18 h, rt. Suzuki cross-coupling of 15a leading to biphenyl derivative 18 and hydrogenolysis to 19. Conditions: a) phenylboronic acid, Pd(PPh3)4, 2 M Na2CO3 aq, THF, 70 °C, 48 h; b) H2, Pd/C, iPrOH, THF

• -coupling of compound 16. Conditions: Pd(PPh3)2Cl2, 2 M Na2CO3, DMF, 80 °C, 3 d. Hydrogenolysis of compound 27 and samarium diiodide-mediated reaction leading to compounds 30 and 31. Conditions: a) H2, Pd/C, TFA, HFIP, iPrOH, 8 h, rt; b) SmI2 (0.1 M in THF), MeOH, 30 min, rt. HFIP = hexafluoro-2-propanol

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

• , 4.5 h; ii. (1) H2, 5% Pd/C, MeOH, 55 °C, 5 h; (2) Dowex 50 W, MeOH, H2O, rt, 4 h. Reagents and reaction conditions: i. pyridine, MgSO4, 100 °C, 28 h, N2; ii. DMF, 70–90 °C, 22–30 h, N2, the cumulative yield of 108/109 from 55% to 96%. Reagents and reaction conditions: i. Montmorillonite K-10 clay

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• . PPh3, Et3N, DMF, 70 °C, 64% yield). The hydrogenation of the so-obtained diene 4 (for its structure see Scheme 1) proceeded smoothly (H2, cat. Pd/C, MeOH, 25 °C, 82% yield) under concomitant removal of the triethylsilyl ether [31] in 12-position to give methyl ester 9 as a single diastereoisomer. At

Pd/C-catalyzed aerobic oxidative esterification of alcohols and aldehydes: a highly efficient microwave-assisted green protocol

• Marina Caporaso,
• Giancarlo Cravotto,
• Spyros Georgakopoulos,
• George Heropoulos,
• Katia Martina and
• Silvia Tagliapietra

Beilstein J. Org. Chem. 2014, 10, 1454–1461, doi:10.3762/bjoc.10.149

• friendly microwave-assisted oxidative esterification of alcohols and aldehydes in the presence of molecular oxygen and a heterogeneous catalysis (Pd/C, 5 mol %). This efficient and ligandless conversion procedure does not require the addition of an organic hydrogen acceptor. The reaction rate is strongly

• catalysts, the common Pd/C is easily handled and filtered off from the reaction mixture. It is remarkably stable under acidic and basic conditions and features a much higher surface area than alumina- and silica-supported catalysts [45]. Moreover, charcoal is rapidly heated under microwave (MW) irradiation

• versatility of these reactors in promoting reactions with gaseous reagents in a closed cavity [56]. In this present work, we report an efficient Pd/C-catalyzed aerobic oxidative esterification of aldehydes and alcohols in the presence of molecular oxygen in a closed MW reactor. The optimized procedure does

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• %); (f) HCO2NH4, Pd/C, MeOH, 1.5 h, reflux, (trans- 92%, cis- 94%); (g) 9, Et3N, n-BuOH, 16 h, 130 °C; (h) KOH, n-BuOH/EtOH, 16 h, 80 °C, (trans- 38%, cis- 50%). Supporting Information Supporting Information File 160: General methods, experimental procedures and copies of 1H/13C NMR spectra and HPLC UV

Synthesis of ethoxy dibenzooxaphosphorin oxides through palladium-catalyzed C(sp²)–H activation/C–O formation

• Seohyun Shin,
• Dongjin Kang,
• Woo Hyung Jeon and
• Phil Ho Lee

Beilstein J. Org. Chem. 2014, 10, 1220–1227, doi:10.3762/bjoc.10.120

• and the LUMO of the Pd–C bond is unfavorable and the Pd–O bond has a significantly ionic character [18][19][20][21][22][23]. To expand this scope, we are interested in the development of C–H activation/C–O formation by means of new directing groups. Recently, a variety of C–H activations by using new

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• corresponding triflate under similar conditions [196][197]. The reaction also proceeded under solvent-free conditions with slightly higher yields [198]. A heterogeneous Pd/C catalyst has been applied as well [199][200]. The group of Glueck has reported the first asymmetric palladium-catalyzed C–P bond formation

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• successfully for the conjugate reduction of a related enoate [35], failed completely in this case and resulted only in the isolation of unreacted starting material. For these reasons we resumed to a hydrogenation catalyzed by Pd/C, in spite of the well-known capricious nature of these transformations [64

• ]. With a commercial sample of Pd on charcoal (10 wt %) a plethora of products was detected, four of which could be isolated and identified as the hydrogenated acetal 11, the methyl ether 13, and the two desilylated products 14 and 15 (Table 3, entry 1). Literature precedence exists for the Pd/C-induced

• dealkoxylation of acetals [65] and for desilylation reactions of silyl ethers [66]. With in situ generated Pd/C (obtained from Pd(OAc)2 and charcoal according to Felpin’s protocol) [67] an improved selectivity was observed as the cleavage of the silyl groups could be suppressed. However, reductive dealkoxylation

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• groups still being protected (Figure 2). Further, oligomers 1 and 7 were debenzylated using H2, 10% Pd/C to β-glycopeptides 2 and 8, respectively. The acetonide groups in the galactosyl and xylosyl sugar units were deprotected simultaneously along with the Boc-groups and cleavage from solid support using

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

• -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

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• -system (4.56, 4.68 ppm). Attempts to initiate the reaction by UV-irradiation (at 20 or 50 °C) or catalysis by compounds of transition metals (Cu(acac)2, Fe(acac)3, Pd(bzac)2, Rh2(AcO)4, Cu(OTf)2, Pd/C) at 20 or 40 °C failed. Benzene was found to be a solvent of choice, and a 1:1 molar ratio of reagents

Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• h; 2) BnBr (1 equiv), n-Bu4NI, 0 °C to rt, 16 h; i: PCC, MS 4 Å, DCM, −20°C, 90 min; j: [(E)-1-methylbut-2-en-1-yl]triphenylphosphonium bromide, n-BuLi, THF, −40 °C, 14 h; k: H2, 20 bar, 10% Pd/C, pentane, rt, 18 h. 70 eV EIMS of synthetic tetramethyltrideca-2,4-dienes 8, 14 and 15. These spectra

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• did not form hydrochlorides under this procedure consistent with the strongly acidic nature of the CF3 phosphinic acid group. Catalytic hydrogenation of intermediates 13a,b with Pd/C removed the benzyl groups and produced the corresponding acids 14a,b in high yields. The hydrophosphinylation of

• catalytic hydrogenation conditions (II). To a solution of compounds, containing N-Bn fragment (5 mmol) in ethanol (10 mL) 10% Pd/C (0.05 g) was added, and the mixture was hydrogenated at room temperature and normal pressure. After ~3 h the precipitation commenced, and water (5 mL) was added to dissolve this

• , determined by 31P and 19F NMR: 13c (<10%). ii) H2, ethanol, catalysis 10% Pd/C, rt, normal pressure, yields: 14a (95%), 14b (90%). Interaction of the acid 1 with tert-butyl benzylidenecarbamate (21). Reagents and conditions: i) an equimolar mixture of reagents, DME, rt, 48 h, under argon atmosphere, 32

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

• ]. While targeting the synthesis of 2a, the Wittig olefination of 3a with n-hexyltriphenylphosphonium bromide and t-BuOK gave olefin 4a as a diasteromeric mixture of Z and E-isomers in the ratio 9.5:0.5 as shown by 1H NMR of the crude product. The catalytic hydrogenation of alkene 4a with 10% Pd/C in

• azido alcohol 9a was oxidized to the corresponding acid by using RuCl3·3H2O/NaIO4 to give 10a [36]. Finally, cleavage of the 2-O-benzyl ether and reduction of the 3-azido group to the corresponding amine in one step with 10% Pd/C in methanol provided (−)-α-hydroxy-β-aminodecanoic acid (AHDA, 2a) in 80

• -pentodialdo-1,4-furanose (3b) which was obtained from D-glucose in good yield as reported earlier [33]. Thus, the Wittig reaction of 3b followed by hydrogenation (10% Pd/C) gave 4-heptyl-D-threose derivative 5b (Scheme 3). Hydrolysis of 1,2-O-isopropylidene (TFA:H2O) followed by oxidative cleavage of the

Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

• Richard J. Ingham,
• Claudio Battilocchio,
• Joel M. Hawkins and
• Steven V. Ley

Beilstein J. Org. Chem. 2014, 10, 641–652, doi:10.3762/bjoc.10.56

• ; H2 pressure: 20 bar and full hydrogen mode; and flow rate: 0.1 mL min−1 and 0.2 mL min−1) suggested 16 experiments – two repeats each of eight sets of conditions. A single catalyst was used, a 10% Pd/C cartridge supplied by ThalesNano. With a large amount of material from the previous step in hand

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