The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• temperature: Azo coupling reaction. PTSA-catalyzed diazotization and azo coupling reaction. Ferric hydrogen sulfate (FHS) catalyzed azo compound synthesis. Synthesis of azo compounds in the presence of silica supported boron trifluoride. Phase transfer catalyzed azo coupling of 5-methylresorcinol in

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• precipitation from the reaction mixture and n-BuOH proved to be the most suitable solvent in the reaction. Performing the reaction in refluxing n-BuOH in the presence of one equivalent of HClO4 for 8 h, compound 1a was obtained in 30% isolated yield. Other acids including p-toluenesulfonic acid (PTSA), HCl, and

• HOAc were also screened, and the results indicated that the use of PTSA led to a slightly decreased yield, and weaker acids failed to promote this process. It is worth noting that the reaction proceeded incompletely and significant amounts of isatin (3a) were recovered. When increased amounts (1.35

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• ) was straightforward. Heating rac-74 with a mixture of acetic anhydride and para-toluenesulfonic acid (PTSA, 1 equiv) afforded via, presumably, protonated rac-75 ring-opened and O-acylated (±)-1-bromo-3-methylbut-3-en-2-yl acetate (rac-76) in a 58% yield. Isolation, solvent removal and purification of

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• ) H2SO4, 70% AcOH, 0 °C → rt, 4 h, 84%; c) 2,2-dimethoxypropane, acetone, PTSA, rt, 4 h, 63%; d) Ac2O, pyridine, CH2Cl2, rt, overnight, 92%; e) MeONa, MeOH, rt, overnight, 97%. Reagents and conditions: a) EtSH, BF3·OEt2, CH2Cl2, −5 °C → rt, 4 h, 13: 55%, 14: 34%. Crystallographic and experimental dataa

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

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• equiv), THF/H2O 3:1 (v/v), 25 °C, 12 h, 70%. (e) 7, Dowex 50, MeOH, reflux, 12 h, 95%. Synthesis of tyrosine-based imidazolidin-4-one 5. Reaction conditions: (a) 9 (1.0 equiv), MeNH2 (5.0 equiv), EtOH, 25 °C, 20 h. (b) PTSA (0.01 equiv), acetone, MeOH, reflux, 18 h, 79% (2 steps). (c) 10 (1.0 equiv

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

• alkene 18 in 95% yield. Protection of the ketone in 18 as the cyclic ketal 19 was achieved in 44% yield using excess ethylene glycol and pTSA and despite attempting a variety of alternate conditions [20][21][22][23] this yield could not be improved without degradation of both the starting material 18 and

• h, 14%. Reagents and conditions: (i) H3C(CH3O)NH·HCl, n-BuLi, THF, −78 °C, 4 h, 81%; (ii) 1-bromo-3,4-methylenedioxybenzene, t-BuLi, THF, −78 °C, 3 h, 84%; (iii) NaH, allyl bromide, TBAI, THF, 65 °C, 20 h, 95%; (iv) ethylene glycol, pTSA, toluene, reflux, 16 h, 44%; (v) OsO4, NMO, t-BuOH, H2O, THF

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

•  7). Compounds 30–34 were obtained through Friedel–Crafts acylation of 29 with corresponding acyl chlorides in 55–81% yield. Subsequent alkylation with geranyl bromide gave products 35–39 in moderate yields from 55 to 60%. Finally, p-toluenesulfonic acid (pTSA)-catalyzed cyclization afforded the

• . Reagents and conditions: (a) acyl chloride, AlCl3, CS2/PhNO2, 55 °, 2 h; (b) geranyl bromide, K2CO3, acetone, reflux, overnight; (c) pTSA, benzene, reflux, 2 h. Synthesis of acylphloroglucinol derivatives 43–51. Reagents and conditions: (a) isoprene, Amberlyst 15, THF/hexane; (b) benzoyl chloride, AlCl3

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• of either a Brønsted or a Lewis acid catalyst (Table 1, entry 1). However, the use of Lewis acids, such as indium(III) salts or TMSCl, improved the reaction rate, with yields up to 67% (Table 1, entries 2–4). The GBB-3CR catalysed by Brønsted acids, including PTSA or HClO4, led to similar yields as

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• ; f) MeLi, Et2O, −78 °C, 1 h. TBDPSCl = tert-butyldiphenylsilyl chloride. Synthesis of substrates 33–35, 37. Reagents and conditions: a) lit. [33] L-proline (0.25 equiv), 2-nitrosotoluene, CHCl3, −18 °C; b) RMgCl, CeCl3·2LiCl, THF, −78 °C to rt, overnight; c) acetone, PTSA, 3 h, rt; d) OsO4 (0.01

• equiv), NMO (2 equiv), pyridine, 5 d, rt; e) NaIO4, MeOH/H2O, 3 h, rt; f) NaH, (EtO)2POCH2CO2Et, THF, −20 °C to rt, 15 min; g) DIBAL-H, CH2Cl2, −30 °C to −10 °C, 45 min; h) Ac2O, pyridine, CH2Cl2, 3 h, rt; i) AcOH/H2O, 3 h, 60 °C. PTSA = p-toluenesulfonic acid, NMO = N-methylmorpholine N-oxide, DIBAL

• = diisobutylaluminium hydride. Synthesis of rac-42. Reagents and conditions: a) MCPBA, CH2Cl2, 0 °C to rt, 45 min; b) TFA, H2O, THF, 60 °C overnight, c) acetone, PTSA, 3 h, rt; d) NaOMe, MeOH, 48 h, rt, 43% over 5 steps; e) (COCl)2, DMSO, Et3N, CH2Cl2, −78 °C to rt, 2 h; f) diethyl allylphosphonate, BuLi, THF, 0 °C to

Homochiral BINOL-based macrocycles with π-electron-rich, electron-withdrawing or extended spacing units as receptors for C₆₀

• Marco Caricato,
• Silvia Díez González,
• Idoia Arandia Ariño and
• Dario Pasini

Beilstein J. Org. Chem. 2014, 10, 1308–1316, doi:10.3762/bjoc.10.132

• ], 3a [28], 4a [28] and p-toluenesulfonic acid 4-dimethylaminopyridinium salt (PTSA-DMAP) [45] were prepared according to literature procedures. THF (Na, benzophenone) and CH2Cl2 (CaH2) were dried before use. Analytical thin-layer chromatography was performed on silica gel, chromophore loaded, and with

• . In a manner similar to the procedure described in [28], a solution of DICD (diisopropylcarbodiimide, 3 equivalents vs diol and dicarboxylic acid) in a minimum amount of dry CH2Cl2 is added to a solution of the appropriate dicarboxylic acid (20–25 mM), (R)-1 (20–25 mM), PTSA-DMAP (2 equivalents) in

• . From 2,5-thiophenedicarboxylic acid (115 mg, 0.67 mmol, 1 equiv), DICD (312 µL, 2.01 mmol, 3 equiv), (R)-1 (250 mg, 0.67 mmol, 1 equiv), PTSA-DMAP (414 mg, 1.337 mmol, 2 equiv). Purified by flash column chromatography (hexanes/EtOAc 8:2 to 7:3) to yield 3b (21 mg, 6%) and 4b (13 mg, 4%) as white solids

Efficient carbon-Ferrier rearrangement on glycals mediated by ceric ammonium nitrate: Application to the synthesis of 2-deoxy-2-amino-C-glycoside

• Alafia A. Ansari,
• Y. Suman Reddy and
• Yashwant D. Vankar

Beilstein J. Org. Chem. 2014, 10, 300–306, doi:10.3762/bjoc.10.27

• of the resulting diol by using 2,2-dimethoxypropane and a catalytic amount of para-toluenesulfonic acid (PTSA) to furnish the desired orthogonally protected 2-deoxy-2-amino-C-glycoside 12 as a single isomer in 82% yield (over 2 steps). The stereochemistry of the newly generated stereocenters in

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

• , 64% (2 steps); for the synthesis of 19: k) DIPEA, MOMCl, CH2Cl2, reflux, 16 h, 99%; l) TBAF, THF, rt, 20 min, 94%; for the synthesis of 20: k) TIPSOTf, 2,6-lutidine, DMF, 0 °C to rt, 3 h, quant.; l) PTSA, MeOH, THF, rt, 30 h, 77%; m) PivCl, DMAP, pyridine, −15 °C to rt, 2 h, 77%; n) NaBH4, CeCl3·7H2O

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• (interplanar angles 22° and 9°). Three of the four NH hydrogens are involved in hydrogen bonds, leading to ribbons of H-bonded rings parallel to the a axis. Following the second route, the 1,3-dipolar cycloaddition, with the purpose of increasing the yield of compound 1, we used p-toluenesulfonic acid (PTSA

• )–ZnCl2 as a catalyst for the synthesis of aniline 1 from amidoximes and organic nitriles [37]. tert-Butylamidoxime and 4-aminobenzonitrile were mixed in DMF with catalytic amounts of PTSA–ZnCl2. First, tert-butylamidoxime is activated by PTSA–ZnCl2; resulting in the formation of a Lewis acid–ammonia

• . After a series of tests by using various acids as catalyst (p-toluensulfonic acid (PTSA), 2-mesitylenesulfonic acid (MSA) and methanesulfonic acid (MeSA) in combination with ZnCl2 and ZnBr2), MSA–ZnBr2 in acetonitrile proved to be the best combination for the preparation of compound 2 from tert

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

• starting material was recovered quantitatively (Table 1, entries 3 and 4). In absence of the gold catalyst no product could be observed (Table 1, entry 5). The application of p-toluenesulfonic acid (PTSA) instead of TFA did not improve the outcome (Table 1, entry 6). Having the optimized conditions in hand

Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

• Qiang Wei,
• Ya-Yi Wang,
• Yu-Liu Du and
• Liu-Zhu Gong

Beilstein J. Org. Chem. 2013, 9, 1559–1564, doi:10.3762/bjoc.9.177

• has been considered to be promising but challenging. Danishefsky found that the treatment of bis(Cbz)tryptamine with N-phenylselenophthalimide (N-PSP) in the presence of a catalytic amount of p-toluenesulfonic acid (PTSA) was able to afford a racemic selenofunctionalization product in 84% yield [28

Re₂O₇-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles

• Wantanee Sittiwong,
• Michael W. Richardson,
• Charles E. Schiaffo,
• Thomas J. Fisher and
• Patrick H. Dussault

Beilstein J. Org. Chem. 2013, 9, 1526–1532, doi:10.3762/bjoc.9.174

• reversibly formed Re(VII) ester [19][20], would enable displacement under milder conditions, potentially allowing access to a broader range of alkoxydioxolanes. As shown in Table 1, the use of Re2O7 or p-toluenesulfonic acid monohydrate (PTSA) as catalysts provided comparable yields in the etherification of

• were curious about the interactions of Re(VII) oxides with hydroperoxyacetals (1-alkoxyhydroperoxides), versatile intermediates available from ozonolysis of alkenes in alcoholic solvents [23][24]. As can be seen in Table 8, Re2O7, Me3SiOReO3 and PTSA all catalyze alkoxide metathesis to furnish a

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

• (Scheme 2). Adding a catalytic amount of Brønsted acid (PTSA) into the reaction system did slightly improve the yield of 3a. Solvent screening demonstrated that dichloromethane was the best choice in the reaction. As revealed in Scheme 2, a variety of allenic carbamates 2 were also suitable for such

• % [AuClPPh3], 2.5 mol % AgOTf, 10 mol % PTSA, CH2Cl2, rt, 3a: 6 h; 3b: 7 h, 3d: 6 h; 3e: 8 h; 3f: 7 h; 3g: 5.5 h; 3h: 5 h; 3i: 7 h; 3j: 2 h. (ii) 2.5 mol % [AuClPPh3], 2.5 mol % AgOTf, 10 mol % PTSA, CH2Cl2, sealed tube, 130 °C, 4a: 1.5 h; 4b: 2 h, 4c: 4 h; 4d: 6 h; 4e: 4 h; 4f: 0.5 h; 4g: 5.5 h; 4i: 2 h

• . (iii) 2.5 mol % [AuClPPh3], 2.5 mol % AgOTf, 10 mol % PTSA, CH2Cl2, sealed tube, 80 °C, 4j: 2 h. PMP = 4-MeOC6H4. Possible explanation for the gold-catalyzed isomerization reaction of 1,3-oxazinan-2-one 3a into 1,3-oxazin-2-one 4a. Reagents and conditions: (i) 2.5 mol % [AuClPPh3], 2.5 mol % AgOTf, 10

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• combination of para-toluenesulfonic acid (PTSA) and benzene was the optimum system for Akiyama and co-workers (Scheme 2). After evaluating different Lewis and Brønsted acids with their equivalents as well as different solvents, Seidel and co-workers found that 0.2 equivalents of triflic acid in ethanol under

• . Akiyama and co-workers screened different Brønsted acid catalysts for their reaction, with PTSA emerging as the most effective catalyst [11]. Employing an optimized set of conditions, the reaction was conducted with different amines, and good to excellent yields (40–92%) were obtained (Scheme 2). A

• more organocatalytic non-asymmetric and asymmetric sp3 C–H activation processes are expected [37]. Triflic acid-catalysed synthesis of cyclic aminals. PTSA-catalysed synthesis of cyclic aminals. Plausible mechanism for cyclic aminal synthesis. Annulation cascade reaction with double nucleophiles

Aldol elaboration of 4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridin-4-ones, masked precursors to acylpyridones

• Raymond C. F. Jones,
• Abdul K. Choudhury,
• James N. Iley,
• Mark E. Light,
• Georgia Loizou and
• Terence A. Pillainayagam

Beilstein J. Org. Chem. 2012, 8, 308–312, doi:10.3762/bjoc.8.33

• elimination under Dean–Stark conditions of water removal (toluene, reflux, PTSA in 2 portions; for quantities see Supporting Information File 1) to deliver more of the condensation products 8c–e (41, 38, 44%, respectively, Table 1, see Supporting Information File 1 for full experimental and spectroscopic data

• conditions (toluene, reflux, PTSA, 1.3 mol equiv) to give the 3-alkenyl compound 8a (63%). This revised protocol has not yet been extended to the reaction of pyridone 6 with other aldehydes, but has been routinely employed for elaboration of the dehydro version 4 [16]. The acylpyridone antifungal natural

• minor product. This dehydration product, 3-alkenylisoxazolopyridone 11, was prepared from the hydroxy adduct 16 by heating under a Dean–Stark water separator (toluene, reflux, PTSA, 1.5 mol equiv; 78%). Conclusion We have thus developed suitable protocols for C-3 elaboration of the 3-methyl-4,5,6,7

Efficient, highly diastereoselective MS 4 Å-promoted one-pot, three-component synthesis of 2,6-disubstituted-4-tosyloxytetrahydropyrans via Prins cyclization

• Naseem Ahmed and
• Naveen Kumar Konduru

Beilstein J. Org. Chem. 2012, 8, 177–185, doi:10.3762/bjoc.8.19

• -hydroxytetrahydropyran in excellent yields (95–96%). Keywords: aromatic homoallylic alcohols; 2,6-disubstituted-4-tosyloxytetrahydropyrans; MS 4 Å; Prins cyclization; PTSA; Introduction Substituted tetrahydropyrans are common structural motifs in numerous biological molecules and natural products that include

• and unsymmetrical tetrahydropyrans can be synthesized. p-Toluenesulfonic acid (PTSA) is reported as a versatile Brønsted acid catalyst in various organic transformations [32][33][34]. Previously, PTSA has been used as a catalyst in Prins cyclizations but the product yields were low even under extended

• nitrogen atmosphere at −78 °C for 2 h [40]. Their structures were assigned by 1H, 13C NMR, IR, and GC–MS data and compared with reported values in the literature. Initially, we carried out the reaction with homoallylic alcohols, aromatic aldehydes and PTSA at room temperature to afford 2,4,6-trisubstituted

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

• ynones were then treated in situ with sodium iodide and PTSA to yield 2-substituted N-Boc-4-iodopyrroles 32 in good overall yields. Interestingly, this product may be further transformed in situ into the corresponding N-Boc-4-alkynylpyrroles 33 by a further Sonogashira coupling that makes use of the

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• homopropargylic alcohols. In the conversion from alkynols 22 to tetrahydrofuryl hemiacetals 23, water is required, which is probably provided by trace amounts of water present in the solvent or the catalyst. Additionally, it should be noted that PTSA contains water since the monohydrate is actually employed. In

• -azetidinone nucleus [66][67]. Treatment of the terminal alkyne 35a with the catalytic system AuCl3/PTSA gave the desired ketal 36a. Appreciable amounts of a polar ketone arising from alkyne hydration were also produced. Fortunately, the [AuClPPh3]/AgOTf/PTSA system demonstrated better activity. Interestingly

An efficient and practical entry to 2-amido-dienes and 3-amido-trienes from allenamides through stereoselective 1,3-hydrogen shifts

• Ryuji Hayashi,
• John B. Feltenberger,
• Andrew G. Lohse,
• Mary C. Walton and
• Richard P. Hsung

Beilstein J. Org. Chem. 2011, 7, 410–420, doi:10.3762/bjoc.7.53

• ). There appears to be some solvent effect on the E/Z selectivity with more polar solvents providing the best ratio (Table 1, entries 2–4). In addition to thermal conditions, we screened several Brønsted acids at room temperature in order to investigate a milder condition. While PTSA resulted in poor E/Z

A short stereoselective synthesis of (+)-(6R,2′S)-cryptocaryalactone via ring- closing metathesis

• Palakodety Radha Krishna,
• Krishnarao Lopinti and
• K. L. N. Reddy

Beilstein J. Org. Chem. 2009, 5, No. 14, doi:10.3762/bjoc.5.14

• presence of PTSA to afford compound 10 in 95% yield, which was regioselectively opened with DIBAL-H to afford the primary alcohol 11 in 92% yield (Scheme 1). The primary alcohol 11 was oxidized under Swern conditions and the crude aldehyde was exposed to the alkynylation reaction directly. Several base

• assigned from the chemical shift of acetonide carbon atoms in 13C NMR spectrum. So, upon deprotection of 7, diol 12 was obtained in good chemical yield (84%) and was further protected with 2,2-DMP, in presence of catalytic amount of PTSA, to furnish compound 13. The analytical data of acetonide 13