Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• . The Ellman group demonstrates the power of their chiral sulfinylimine protocol to synthesize propargylamine-derived alpha-tetrasubstituted triazoles (tetrasubstituted carbon bearing amine highlighted in red, Figure 1). One such triazole is a cruzain inhibitor with activity against parasite Trypanosoma

• ]. The lengthy synthesis of tetrasubstituted propargylamine precursors limits the exploration of such alpha-tetrasubstitued triazoles. The vast majority of three-component couplings produce trisubstituted propargylamines. Copper remains the most popular catalyst for these multicomponent reactions

• development of a method for the one-pot deprotection/CuAAC began with Cu(I) chloride and a survey of solvents reported [2] for triazole formation (Table 1). TIPS-protected propargylamine 4a and benzyl azide (5a) are heated in the presence of 1.5 equivalents of TBAF (tetrabutylammonium fluoride), 5 mol % CuCl

Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?

• Tobias-Elias Gloe,
• Insa Stamer,
• Cornelia Hojnik,
• Tanja M. Wrodnigg and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 1096–1104, doi:10.3762/bjoc.11.123

• efficient and versatile approach towards D-manno-configured C-glycosyl-type glycoconjugates. In our study, we have employed two different amines in the Amadori rearrangement with 8, propargylamine and aniline. Under typical conditions for this reaction [2] 1-progargylamino-1-deoxy-D-manno-heptulose 9 and 1

• -phenylamino-1-deoxy-D-manno-heptulose 10 were obtained as pure α-anomers in 77% and 24% yield, respectively (Scheme 3). The low yield of compound 10 may be explained by the low pKa value (4.62) of aniline compared to a pKa of 8.15 for propargylamine, the latter being clearly more efficient as a nucleophile

• for manno-configured C-glycosyl-type hexoses via the Amadori rearrangement was reported. We have employed propargylamine and aniline to prepare 9 and 10, respectively. They carry an anomeric hydroxy group positioned to the α-face of the sugar ring and a rather bulky β-positioned alkyl/aryl aminomethyl

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• alkyne by oxidative amidation using carbon tetrachloride with propargylamine. The microwave-assisted click-conjugation was performed on a solid phase upon completion of the DNA synthesis (Scheme 4). Lönnberg and co-workers prepared a thymidine modified at the 4’-position with an azidomethyl group to

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• monomers eligible for dimerizations by Glaser coupling, equimolar amounts of propargylamine (3), aldehyde 4, carboxylic acid 5, and isocyanides 6 were reacted in methanol at room temperature over 24 h following well established Ugi protocols [12]. After flash column chromatography N-propargyl peptoids 7a–j

Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

• María Emilia Cano,
• Rosalía Agusti,
• Alejandro J. Cagnoni,
• María Florencia Tesoriero,
• José Kovensky,
• María Laura Uhrig and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 3073–3086, doi:10.3762/bjoc.10.324

• azide precursor and then treated with succinic anhydride to afford 2 in excellent yield, using a methodology similar to that previously described [38]. Reaction with propargylamine in the presence of DCC yielded precursor 3. A similar procedure applied to the lactosylamine derivative 4, led to compound

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• hydrogenation of the latter with Lindlar catalyst afforded 7 almost quantitatively. Likewise, copper(I)-catalyzed 1,3-dipolar cycloaddition (Click reaction) [15][16][17][18] of 5 with Fmoc-protected propargylamine afforded first t-butyl benzoate 8 in 87% yield. Hydrogenation of the latter with Pd on charcoal

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

• /aromatization sequence (propargylamine, cat. Na[AuCl4]·2H2O, EtOH, 100 °C) [37][38] furnished, after removal of the tert-butyldimethylsilyl ether (tetrabutylammonium fluoride, THF, 25 °C), carbacyclopamine analog 2 in 36% overall yield for the two steps [39]. Carbacyclopamine analog 2 was then tested for its

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• -mer mannosylated dendrimer 23 is shown in Scheme 5. The synthesis of 5 was accomplished starting from commercial trimesic acid chloride 1 which was readily transformed into known tripropargyl amide derivative 2 [33] using propargylamine according to Scheme 1. Amide 2 was conjugated to peracetylated 2

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• -yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate. (a) bromoacetic acid, DIPEA, CH2Cl2; (b) propargylamine (10 equiv), DMF; (c) bromoacetic acid, DIC, DMF; (d) CH2Cl2/HFIP (4:1); (e) HATU, DIPEA, DMF. Synthesis of DNJ clusters 10: (a) CuSO4·5H2O cat., sodium ascorbate, DMF/H2O (5:1), MW, 80 °C; (b

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• was proven to be necessary in the reaction system. A series of experiments with 1-, 2- or 5-formylimidazoles and selected control reactions with the isolated propargylamine intermediate, partly in the presence of D2O or H218O, were helpful to clarify the mechanism of the formation of pyrrole-2

• -carboxaldehydes and its byproduct. Key steps of the process are the silver-catalyzed intramolecular cyclization of propargylamine followed by a competitive 1,3- or 1,5-isomerization and a subsequent hydrolysis, yielding the pyrroloimidazolone 5 or the pyrrole 4, respectively (Scheme 5). The 1,5-isomerization path

• them on a mesoporous support, i.e., MCM-41. The authors tested them in A3-couplings and found that, although under homogeneous conditions the conversion to the respective propargylamine was higher than under heterogeneous ones, the heterogenized complexes were stable, recyclable for at least six cycles

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• , Department of Chemistry, University of Delhi, Delhi-110 007, India Chemistry Building-4.20b, School of Chemistry, The University of Manchester, Manchester M13 9PL, UK 10.3762/bjoc.9.246 Abstract An Ugi four-component reaction of propargylamine with 3-formylindole and various acids and isonitriles produces

• Ugi-4CR of indole-3-carboxaldehyde (1a), propargylamine (2a), phenylacetic acid (3a) and tert-butylisonitrile (4a) in methanol at 50 °C gave the Ugi-adduct 5a with an excellent yield of 94%. With compound 5a in hand we were keen to apply the previously developed conditions for intramolecular

Gold-catalyzed oxycyclization of allenic carbamates: expeditious synthesis of 1,3-oxazin-2-ones

• Benito Alcaide,
• Pedro Almendros,
• M. Teresa Quirós and
• Israel Fernández

Beilstein J. Org. Chem. 2013, 9, 818–826, doi:10.3762/bjoc.9.93

• , alkynylcarbamates 1a–g were prepared through reductive amination of the appropriate aldehyde with propargylamine, followed by Boc2O treatment of the corresponding N-substituted prop-2-yn-1-amine. Alkynylcarbamate 1h was prepared from Garner’s aldehyde following a literature report [56][57]. Alkynylcarbamate 1i was

• /def2-SVP//B3LYP/def2-SVP level. Preparation of allenic carbamates 2a–j. Reagents and conditions: (i) Propargylamine, MgSO4, CH2Cl2, rt, 15 h. (ii) NaBH4, MeOH, rt, 0.5 h. (iii) Boc2O, Et3N, CH2Cl2, rt, 2–15 h. (iv) (CH2O)n, iPr2NH, CuBr, 1,4-dioxane, reflux, 1 h. (v) Ohira–Bestmann reagent, K2CO3, MeOH

Tandem aldehyde–alkyne–amine coupling/cycloisomerization: A new synthesis of coumarins

• Maddi Sridhar Reddy,
• Nuligonda Thirupathi and
• Madala Haribabu

Beilstein J. Org. Chem. 2013, 9, 180–184, doi:10.3762/bjoc.9.21

• the assistance of the work reported by Patil et al. [24][32]). Initial condensation of pyrrolidine with salicylaldehyde 1 produced iminium intermediate A. The addition of copper ethoxyacetylide, formed on the reaction of ethoxyacetylene with Cu, to the iminium intermediate A yielded propargylamine

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• (amination) a primary amine is used to substitute the bromine to give the peptoid residue. This approach avoids the use of N-terminally protected monomers, which have to be synthesized in advance. For the incorporation of the alkyne side chains we chose propargylamine as building block. A sixfold repetitive

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• , analysis of the library yields indicates that N-arylpiperazines A8 and A9 in addition to propargylamine A15 were the most problematic. Perhaps unsurprisingly, the amine that provided the highest yields and highest success rate was diallyl amine, which was used for initial validation of the Chemspeed method

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• general procedure C, beginning with 8a (80 mg, 0.20 mmol, 1.0 equiv) and N-methyl-propargylamine (16.7 mg, 0.24 mmol, 1.2 equiv). Purification by flash chromatography, Rf 0.54 (DCM/EtOAc, 10:1, 83 mg, 0.19 mmol, 98% yield) gave 13a as a brown-orange oil: IR (neat): 2933, 1655, 1370, 1192, 1178, 732, 666

Access to pyrrolo-pyridines by gold-catalyzed hydroarylation of pyrroles tethered to terminal alkynes

• Elena Borsini,
• Gianluigi Broggini,
• Andrea Fasana,
• Chiara Baldassarri,
• Angelo M. Manzo and
• Alcide D. Perboni

Beilstein J. Org. Chem. 2011, 7, 1468–1474, doi:10.3762/bjoc.7.170

• considerations, the N-propargyl amides of 1H-pyrrole-2-carboxylic acids 1a,b, easily prepared in high yields from the corresponding 1H-pyrrole-2-carboxylic acids and N-methyl-N-propargylamine with DCC as coupling reagent, were submitted to gold-catalyzed reactions under different conditions (Table 1). First, it

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• group 31, which will undergo addition–intramolecular cyclocondensation processes leading to the formation of pyrrole derivatives. For instance, a series of (hetero)aryl-, alkynyl-, and cycloalkyl acid chlorides were cross-coupled with N-Boc-protected propargylamine at room temperature, and the resulting

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

• substantially less nonspecific interaction with proteins over other fluorescent dyes [45]. Using alkynyl-NBD 30 (prepared in one step from NBD chloride and propargylamine) [34], the disaccharide 1 and trisaccharides 2 and 3 were coupled upon treatment with CuSO4, sodium ascorbate and the Cu(I)-stabilizing

Synthesis of new triazole- based trifluoromethyl scaffolds

• Michela Martinelli,
• Thierry Milcent,
• Sandrine Ongeri and
• Benoit Crousse

Beilstein J. Org. Chem. 2008, 4, No. 19, doi:10.3762/bjoc.4.19

• ) species can be used directly (e.g. CuI), or generated by oxidation of a Cu(0) or reduction of a Cu(II) species. Catalysis by the CuI is known to yield exclusively the 1,4-disubstituted regioisomer [33][34]. First, the N-(p-methoxyphenyl)-1-(trifluoromethyl)propargylamine was reacted with benzyl azide in

• applied our strategy to the enantiopure trifluoromethyl-propargylamine 3 bearing the removable (R)-phenylglycinol chiral auxiliary (Scheme 2) [30][31][32]. The reaction was carried out under the same condition with azidoacetic acid methyl ester and afforded the cycloadduct 4 in good yield (79%) and as a

• . Experimentally found NOE correlation for compound 2c. Synthetic approach to the trifluoromethyl triazoles. Cycloaddition of enantiopure propargylamine. Copper(I)-catalyzed synthesis of 1,4-disubstituted triazoles Supporting Information Supporting Information File 50: General methods, synthetic procedure and