Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• proceeded well and afforded the expected 5-(1,2,3-triazolyl)-substituted 1,2-oxazine syn-26 in moderate yield (54%). Hydrogenolysis belongs to the well-established transformations of 1,2-oxazines, often successfully leading to valuable compounds including 1,4-amino alcohols or pyrrolidine derivatives. We

• therefore briefly examined the reaction of 5-aryl-substituted 1,2-oxazines syn-21 and anti-24 under previously established conditions [53]. The hydrogenolysis of 1,2-oxazine derivative syn-21 in methanol using palladium on charcoal as catalyst afforded the expected α-(3-methoxyphenyl)-substituted γ-amino

• 95:5). In contrast, when these hydrogenolysis conditions were applied to the D-arabinose-derived 5-phenyl-1,2-oxazine anti-24 merely an inseparable complex mixture of products was obtained. After shortening of the reaction time from one day to one hour, we were able to isolate two products, the N

Regiocontroled Pd-catalysed C5-arylation of 3-substituted thiophene derivatives using a bromo-substituent as blocking group

• Mariem Brahim,
• Hamed Ben Ammar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2016, 12, 2197–2203, doi:10.3762/bjoc.12.210

• -phenylthiophene (27) in 60% yield. A higher yield of 80% in 28 was obtained for the coupling of 16 with phenylboronic acid. In order to further demonstrate that a bromo-substituent at C2-position of the thiophenes can be considered as a protecting group, we removed it via palladium-catalysed hydrogenolysis

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• (6) (Scheme 4). It was also possible to produce another carbohydrate using the same synthetic pathway. Thus, mono-protection of THF diol 5 followed by oxidation of the remaining free primary hydroxy group to the carboxylic acid and a final hydrogenolysis gave (+)-D-chitaric acid (7) with a yield of

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

• ] with bisoxazoline catalyst 33, we have assigned the S,S configuration to the major isomer of product 32. By hydrogenolysis, we could now convert such a sample (40% ee) into 25. The product S,S-25 was formed as the dominant product (35% ee) thus confirming our previous assignment. Under mild basic

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• -oxazolopiperidines 52 with 58% yield and 79:21 dr. Further reduction and hydrogenolysis of 52 in the presence of Pd/C led to aminoester 53 which was converted to (S)-piperidin-2-phosphonic acid (54) through acidic hydrolysis and subsequent treatment with propylene oxide in 42% overall yield and 58% ee (Scheme 13

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• presence of a catalytic amount of Pd on activated charcoal under hydrogenolysis. Thus, we explored the substrate scope using β-N-arylamido benzyl ester or β-N-arylamido p-methoxybenzyl ester as starting materials for the oxidative coupling reaction shown in Figure 2. Towards this end, β-N-aryl amido

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• diastereoselectively converted with a Grignard reagent into the amine 53 as a key step of the synthesis [78]. Cbz protection followed by ozonolysis with subsequent reductive amination and hydrogenolysis led to the 1,3-diamine 54. The cyclisation to the guanidine functionality was achieved with the novel

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• in terms of product purity. Hydrogenolysis of 42 on palladium in ethanol/HCl followed by acetylation of the amino group furnished the target acetylated 3-fluoro-D-GlcNAc 5 as a chromatographically separable mixture of anomers (Table 1). Addition of HCl was found necessary to effect a clean

Diversity-oriented synthesis of analogues of the novel macrocyclic peptide FR-225497 through late stage functionalization

• Jyotiprasad Mukherjee,
• Suman Sil and
• Shital Kumar Chattopadhyay

Beilstein J. Org. Chem. 2015, 11, 2487–2492, doi:10.3762/bjoc.11.270

• solution phase peptide coupling between L-Phe-D-Pro-OMe (6) (prepared by hydrogenolysis of the corresponding carbamate 5) and L-Cbz-Phe-OH (7) followed by elaboration of the resulting tripeptide 8 via N-terminus deprotection leading to 9 followed by a second peptide coupling of the latter with the known

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

• 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

• minutes, giving 14 in an excellent 94% yield. Hydrogenolysis of the alkene in 14 using Pd/C in MeOH proceeded in 2 hours, providing alcohol 15 which was then oxidised to the desired ketone 13 with Dess–Martin periodinane in 75% yield over two steps. Although this approach was ultimately two steps longer

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• -trichloroethyl)malonate to give the mixed malonyl derivatives 8a and 9a, respectively, were followed either by a palladium-catalyzed hydrogenolysis of the benzyl moiety to give 8b [26], or by a selective chemical removal of 2,2,2-trichloroethanol with Zn/AcOH to give 9b [27]. c) Enzymatic synthesis of symmetric

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

• 328 in ethanol saturated with ammonia was heated in a stainless sealed tube for 3 days to deliver the pyridinone derivative 329 (87%). Further, chlorination of the pyridinone 329 afforded the chloropyridine 330 (93%). Subsequently, hydrogenolysis of the pyridine derivative 330 gave the target

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• with reduced double bond. Then we tried a transfer hydrogenolysis method using ammonium formate/10% Pd/C [27], but the result was not improved. The desired product icaritin (3) was finally obtained in 84% yield from 10 when we used 1,4-cyclohexadiene/10% Pd/C in MeOH [28]. Hence, we optimized a

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• -opened unstable diformyl intermediate (I1), which after work-up was immediately used without further purification (for several similar types of acyclic diformyl intermediates, see references [40][41][43][44]). Thus, the crude material was submitted to catalytic hydrogenolysis and after N-deprotection

• hydrogenolysis, followed by reductive cyclization, to give the corresponding indolizidine ester (±)-9 in 40% yield. Finally, ester reduction with LiAlH4 in THF resulted in epitashiromine (±)-10 [32][34][39] in 53% yield after isolation by chromatography (Scheme 3). The stereochemistry of (±)-epitashiromine was

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• the configuration at position 4 resulting in a complex diastereomeric mixture. Alternatively, reduction of menthone oxime can be achieved, either employing Bouveault–Blanc conditions [41], or via hydrogenolysis at a transition metal catalyst [42]. Both approaches lead to the desired product as a

Selective methylation of kaempferol via benzylation and deacetylation of kaempferol acetates

• Qinggang Mei,
• Chun Wang,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 288–293, doi:10.3762/bjoc.11.33

• of dimethyl sulfate at room temperature provided 10 with a yield of 85%. The final deprotection of 10 involving deacetylation with 7.0 M methanolic ammonia and debenzylation by hydrogenolysis with 10% palladium on carbon in EtOAc/MeOH (1:3) at room temperature afforded 12 (Scheme 2). In order to

• sulfate and K2CO3 in acetone/MeOH at reflux afforded 17 in high yield (82%). Subsequent hydrogenolysis of 17 catalyzed by 10% palladium on carbon in EtOAc/MeOH (1:3) at room temperature provided 18 (Scheme 2). Synthesis of 3,4′-di-O-methylkaempferol (22) and 3,4′,5,-tri-O-methylkaempferol (23) 3,4′-Di-O

• -methylkaempferol (22) and 3,4′,5-tri-O-methylkaempferol (23) were prepared from 19 derived from 8. Controlled di-O-methylation and tri-O-methylation of 19 were achieved by the quantity of Me2SO4, resulting in 20 and 21, respectively. Hydrogenolysis of 20 and 21 afforded 22 and 23 (Scheme 3). All the synthetic

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• product 19. Dihydroxylation of 19, followed by oxidative cleavage of the resultant diol gave aldehyde 20 in 80% yield over two steps. Addition of lithiate 16 to aldehyde 20 gave alcohol 21 in 87% yield as an inseparable 1:1 mixture of diastereoisomers. Hydrogenolysis of the benzyl ether in 21 gave ketal

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• starting material, one challenge was to avoid unwanted side reactions resulting from the generation of formaldehyde in the reaction mixture. Hydrogenolysis of the BOM group affords toluene and formaldehyde as byproducts, and the Cbz-deprotected 6'-amino group can undergo unwanted reductive amination, i.e

• ., methylation, with the liberated formaldehyde. Our method to prevent this side reaction was to include an excess of n-butylamine as an additive in the reaction mixture of the hydrogenolysis step. This way, the formaldehyde methylated the added n-butylamine, furnishing a reasonably volatile byproduct [38][48

• heterogeneously catalyzed hydrogenolysis reactions with palladium catalysts. Therefore, the absence of the BOM group was not advantageous for the deprotection step following the asymmetric hydrogenation reaction. The second challenge on the way to target phosphoramidites 7 was the synthesis of protected 3'-amino

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• steps. The selective reduction of the isopropenyl double bond over a Pt/C catalyst resulted in 8A–D. The subsequent removal of the benzyl groups by hydrogenolysis over palladium on carbon (Pd/C) in a 1:1 mixture of n-hexane/EtOAc for 24 h gave primary amino esters 9A–D in excellent yields. The final

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• prepared in excellent yield and ee by alkylation of carboxy-lactam 49 (see Scheme 11) [84]. Oxidative cleavage of the terminal double bond and subsequent reduction with LiAlH4 afforded N-benzylpiperidine-alcohol 56 [84]. Hydrogenolysis of the N-benzyl group and re-protection with di-tert-butyl dicarbonate

N–O Cleavage reactions of heterobicycloalkene-fused 2-isoxazolines

• Jaipal R. Nagireddy,
• Geoffrey K. Tranmer,
• Emily Carlson and
• William Tam

Beilstein J. Org. Chem. 2014, 10, 2200–2205, doi:10.3762/bjoc.10.227

• isoxazoline-cleavage methodology to the preparation of biologically active natural products, including novel antibacterial, antifungal and anticancer treatments [8][9][10][11]. Some common methods of reductive N–O bond cleavage in isoxazolines include hydrogenolysis using Raney nickel, reduction by LiAlH4

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

• tricarballylic acid intermediate. Conversion of the free carboxylic acid moieties into their benzyl esters followed by cleavage of the tert-butyl ester gave 108. This fragment was then coupled with diol 109 to afford the fully protected fumonisin B2 precursor 110. Final hydrogenation and hydrogenolysis of all

• tricyclic intermediate 121. Cleavage of the TBS ethers and hydrogenolysis of the benzyl ester in presence of amidine 122 yielded trinem 23a as its amidinium salt 123. Trinem 123 exhibited antibacterial activity against a variety of strains, with MIC’s of 1.0 μg/mL against Staphylococcus aureus 853E and 0.1

• work-up provided alcohol 141. Coupling under Mitsunobu conditions with an appropriate alcohol, e.g., 3-hydroxypyridine, reduction of the tert-butyl ester with DIBAL-H, and treatment with TBS triflate gave silyl ether 142. Hydrogenolysis of 142 using Pd/BaSO4 produced the free aziridine, which was then

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

• -couplings to form biphenyl aminopyran or p-terphenyl-linked dimers. Hydrogenolysis afforded new unnatural aminosugar mimetics. Zinc in the presence of acid or samarium diiodide were examined for the N–O bond cleavage in order to obtain the rigid p-terphenyl-linked C-glycosyl dimers. Keywords: carbohydrate

• mimetics; hydrogenolysis; multivalent glycosystems; 1,2-oxazines; samarium diiodide; Suzuki cross-coupling; Introduction Carbohydrates are the class of biomolecules with the highest structural diversity [1][2]. Specific carbohydrates are responsible for cell-type specific interactions [3] and they are

• provided compound 16 in 83% yield. This protecting group should allow its removal together with the benzyl group during hydrogenolysis. Surprisingly, a benzyl protection under the same conditions was not possible. Before approaching divalent compounds such as 1 we wanted to convert our building blocks into

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

• precursors to a variety of compounds. The transformations leading to thymidine or its derivatives 3 involved: (a) the metal-catalyzed hydrogenolysis of products 2 [51][52][54][55] (or their 5-(4-tolylthio)methyl derivatives [57]), or (b) the reduction of methylammonium iodides derived from compounds 2 with

• total yield of 45%. The cyclohexylidene protecting group was then removed in refluxing aq AcOH. The resulting diastereoisomers 39 were separated by reversed phase HPLC to yield two pure isomers and the remaining two as an inseparable 1:1 mixture. These were further deprotected by hydrogenolysis under

Unusual polymorphism in new bent-shaped liquid crystals based on biphenyl as a central molecular core

• Anna Kovářová,
• Svatopluk Světlík,
• Václav Kozmík,
• Jiří Svoboda,
• Vladimíra Novotná,
• Damian Pociecha,
• Ewa Gorecka and
• Natalia Podoliak

Beilstein J. Org. Chem. 2014, 10, 794–807, doi:10.3762/bjoc.10.75

• –c to yield the phenyl esters 17a–c. In the next step, the hydroxylic group was released by the palladium-catalysed hydrogenolysis of the benzyl group and the formed phenols 18a–c were acylated with acids 8–10 to produce the series of compounds IV–VI. For clarity, chemical formulae of the studied