Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• over the time (Scheme 4). Within our proposed catalytic cycle, when compound 4j is utilized, methanol is released, due to the presence of a dimethyl acetal residue. Therefore, using molecular sieves (MS 4 Å) little alcohol molecules, such as MeOH, can be potentially trapped, allowing the insertion of a

• more encumbered alcohol, such as benzyl alcohol, which is not sequestered by MS 4 Å. As a matter of fact, the new benzylated N,O-aminal 7 was successfully obtained in 70% isolated yield as the sole product (experiment D, Scheme 5). In this latter case, the benzyl alcohol presumably reacts with the

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• % yield (Table 1, entry 3). The yield of 2a could be improved to 30% by adding MS 4 Å to the reaction mixture (Table 1, entry 4). Screening of various solvents revealed that THF was the best choice for this reaction (Table 1, entries 4–11), and the yield of 2a was dramatically improved to 89% (Table 1

• , entry 11). In the absence of MS 4 Å, the yield of 2a was diminished even when the reaction was carried out in THF (Table 1, entry 12). With the optimized reaction conditions in hand, we examined the one-pot synthesis of 2a from methyl ester 7a. Methyl 2-pyridylacetate 7a were saponified with lithium

• hydroxide in a MeOH/H2O system. After completion of the reaction, the solvents were evaporated under reduced pressure. Then, THF, MS 4 Å, and 6 were added to the residue, and the mixture was stirred at room temperature for 8 h. This reaction successfully afforded the desired product 2a in 85% yield over two

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• , DMAP, CH2Cl2, rt, 85%; (h) Zn/AcOH, CH2Cl2, rt; (i) DIPEA, FmocCl, CH2Cl2, rt, 80% (2 steps); (j) PhBCl2, Et3SiH, CH2Cl2, MS 4 Å, −78 °C, 80%; (k) HF/pyridine, THF,−40 °C to rt, 93%; (l) DBU, ClCN(Ph)CF3, CH2Cl2, 95%. Synthesis of lipid X monosaccharide 1. Conditions: (a) Zn, AcOH, CH2Cl2, rt; (b) acid

Synthesis of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71^T using linear and one-pot iterative glycosylations

• Arin Gucchait,
• Pradip Shit and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 1700–1705, doi:10.3762/bjoc.16.141

• (10 mL) was added activated MS 4 Å (500 mg) and the mixture was cooled to −15 °C under Ar. To the cold reaction mixture was added NIS (360 mg, 1.6 mmol) followed by HClO4-SiO2 (40 mg), and the mixture was stirred at the same temperature for 30 min. After complete consumption of compound 3 [TLC; hexane

• (515 mg, 1.01 mmol) in anhydrous CH2Cl2 (10 mL) was added activated MS 4 Å (500 mg) and the mixture was cooled to −15 °C under Ar. To the cold reaction mixture was added NIS (230 mg, 1.02 mmol) followed by HClO4-SiO2 (30 mg) and it was stirred at the same temperature for 30 min. After complete

• -glucopyranoside (7): To a solution of compound 6 (600 mg, 0.57 mmol) and compound 4 (270 mg, 0.63 mmol) in anhydrous CH2Cl2 (10 mL) was added activated MS 4 Å (500 mg) and the mixture was cooled to −15 °C under Ar. To the cold reaction mixture was added NIS (150 mg, 0.67 mmol) followed by HClO4-SiO2 (20 mg) and

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• visualized targets. Reaction conditions: a) MeOH, H2SO4 (5 drops), MS 4 Å (2 pieces), 68 °C, 8 h, 81%; b) DIBAL-H (1.2 equiv), 6 h, −78 °C, THF, 78%; c) phosphorane 8 (2.0 equiv), THF, 8 h, 60 °C, 72%; d) SeO2, dioxane, 110 °C, 8 h, 61%; e) indolamine 10 (1.1 equiv) DCE, sodium triacetoxyborohydride (STAB

Convenient synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia albertii O4

• Tapasi Manna,
• Arin Gucchait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 106–110, doi:10.3762/bjoc.16.12

• synthetic intermediates. (a) NIS, HClO4/SiO2, MS 4 Å, CH2Cl2, −45 °C, 1 h, 79%; (b) 0.1 M CH3ONa, CH3OH, room temperature, 2 h, 95%. (a) HClO4/SiO2, CH2Cl2, −10 °C, 1 h, 76%. (a) NIS, HClO4/SiO2, MS 4 Å, CH2Cl2, −40 °C, 1 h, 22%. (a) NIS, HClO4/SiO2, MS 4 Å, CH2Cl2, −45 °C, 1 h, 74%; (b) BnBr, NaOH, TBAB

• , THF, room temperature, 6 h; (c) DDQ, CH2Cl2/H2O (9:1), room temperature, 2 h, 72% in two steps; (d) HClO4/SiO2, CH2Cl2, −10 °C, 1 h, 76%; (e) 0.1 M CH3ONa, CH3OH, room temperature, 2 h, 94%; (f) NIS, HClO4/SiO2, MS 4 Å, CH2Cl2, –15 °C, 1 h, 70%; (g) CH3COSH, pyridine, room temperature, 16 h; (h

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• temperature, 2 h, 98%. Reagents and conditions: (a) Benzoyl chloride, pyridine, 0 °C, 3 h, 75%; (b) Tf2O, BSP, TTBP, CH2Cl2, MS 4 Å, −60 °C, 1 h then compound 10, −78 °C, 2 h, 65%; (c) PdCl2, CH3OH, 0 °C to room temperature, 3 h, 75%; (d) CCl3CN, DBU, CH2Cl2, −10 °C, 90% (mixture of α and β). Reagents and

• conditions: (a) TMSOTf, CH2Cl2, −10 °C, 30 min, 45%; (b) NIS, TMSOTf, MS 4 Å, CH2Cl2, −10 °C, 30 min, 40%. Reagents and conditions: (a) NIS, TMSOTf, MS 4 Å, CH2Cl2, −50 °C, 2 h, 70%; (b) benzyl bromide, NaOH, TBAB, DMF, 3 h; (c) DDQ, CH2Cl2/H2O, room temperature, 84%; (d) TMSOTf, CH2Cl2, −10 °C, 30 min, 70

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• cooled to 0 °C in the intermediate storage tank T5. The reaction mixture can pass through separator S1 (adsorption column) which is packed with MS 4 Å to remove the byproduct water. A solution of malonate and triethylamine in toluene are precooled to 0 °C in feed storage tanks and pumped to mixer M6

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• ) with MS 4 Å. Asymmetric ring opening of meso-epoxides by p-xylenedithiol catalyzed by a (S,S)-(salen)Cr complex. Desymmetrization of meso-epoxide with thiophenol derivatives. Enantioselective ring-opening reaction of meso-epoxides with ArSH catalyzed by a C2-symmetric chiral bipyridyldiol–titanium

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• NMR (Scheme 21a). The formation of the glycosyl chloride was possibly due to the presence of Lewis basic molecule sieves (MS 4 Å) in the reaction system lowering the reactivity of AgOTf [18]. As a result, p-TolSCl could directly activate the glycosyl donor forming glycosyl chloride due to the higher

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• reagent, DME, rt, 36 h, 72%. Synthesis of the heterocyclic core of the D-series GE2270. Reaction conditions: a) TBDMSOTf, NEt3, DCM, 0 °C, 1 h, 51%. b) NBS, THF, 1 h, 94%. c) 16, MS 4 Å, DMF, 0 °C, 14 h, then 2,6-lutidine, TFAA, DME, −20 °C, 12 h, 85%. Supporting Information Supporting Information File

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

• Masahiro Torii,
• Kohsuke Kato,
• Daisuke Uraguchi and
• Takashi Ooi

Beilstein J. Org. Chem. 2016, 12, 2099–2103, doi:10.3762/bjoc.12.199

• the presence of a catalytic amount of chiral ammonium betaine 1a (5 mol %) in toluene with 4 Å molecular sieves (MS 4 Å) at −60 °C. Bond formation occurred smoothly and, after 24 h of stirring, the desired Mannich adduct 4aa was isolated as a mixture of diastereomers in 90% yield. Although the

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• reactions were performed in trifluorotoluene at room temperature with the Michael acceptor 30 (R1, R2, R3 = Me, H, Me) and O-benzylhydroxylamine (31, R4 = PhCH2), using a stoichiometric amount of the chiral activator and MS 4 Å as an additive. Some of the reported experiments supported the ability of the

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

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• ) aq 80% AcOH, 3 h, 90 °C; ii) TrtCl, 4-DMAP, pyridine, 24 h, 50 °C, 83% (2 steps); (D) i) Tf2O, pyridine, CH2Cl2, 2 h, 0 °C; ii) TBAF, MS 4 Å, THF, 3 h, rt, 70% (2 steps); iii) aq 80% AcOH, 4 h, 90 °C; iv) Ac2O, pyridine, 4-DMAP, 12 h, rt, 78% (2 steps); (E) AgOTf, NIS, MS 4 Å, 24 h, 0 °C, 80%; (F) i

Synthesis of the pentasaccharide repeating unit of the O-antigen of E. coli O117:K98:H4

• Pintu Kumar Mandal

Beilstein J. Org. Chem. 2014, 10, 2724–2728, doi:10.3762/bjoc.10.287

• . Reagents: (a) N-iodosuccinimide (NIS), TMSOTf, CH2Cl2, MS 4 Å, −30 °C, 1 h, 72%; (b) HClO4/SiO2, CH3CN, rt, 20 min, 85%; (c) benzoyl cyanide, DCM/pyridine, rt, 2 h, 80%; (d) N-iodosuccinimide (NIS), TfOH, CH2Cl2, MS 4 Å, −30 °C, 1 h, then 0 °C, 1 h, 77%; (e) NOBF4, Et2O/CH2Cl2 (3:1), −15 °C, 1 h, 75%; (f

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

• , 10 h; c: p-TsCl, DMAP, TEA, DCM, −20 °C to rt, 12 h; d: (3-methylbutyl)magnesium bromide, CuI, THF, −90 °C to rt, 16 h; e: TBAF, THF, rt, 14 h; f: PDC, MS 4 Å, DCM, −20 °C, 90 min; g: (3-methylbut-2-en-1-yl)triphenylphosphonium bromide, n-BuLi, THF, −40 °C to rt 16 h; h: 1) NaH, THF, −20 °C to rt, 1

• 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

• ; b: 1) DIAD, TPP, THF, −20 °C, 30 min; 2) 3,5-DNBA, rt, 40 min; 3) 17, rt, 17 h; c: 2 N NaOH aq, THF/MeOH, rt, 45 min; d: MsCl, TEA, DCM, −80 °C, 2 h; e: n-propylmagnesium bromide, CuI, THF, −90 °C to rt, 48 h; f: p-TsOH, MeOH/THF/H2O, rt, 2 h; g: PDC, MS 4 Å, DCM, −20 °C, 90 min; h: [(E)-1-methylbut

Convergent synthesis of a tetrasaccharide repeating unit of the O-specific polysaccharide from the cell wall lipopolysaccharide of Azospirillum brasilense strain Sp7

• Pintu Kumar Mandal,
• Debashis Dhara and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2014, 10, 293–299, doi:10.3762/bjoc.10.26

• (8): To a solution of compound 2 (1.5 g, 4.00 mmol) and compound 3 (2.2 g, 4.80 mmol) in anhydrous CH2Cl2 (10 mL) was added MS 4 Å (2 g), and the reaction mixture was stirred under argon at room temperature for 30 min and cooled to −30 °C. To the cooled mixture were added NIS (1.3 g, 5.76 mmol) and

• mmol) and compound 5 (1.03, 2.16 mmol) in anhydrous CH2Cl2/Et2O (15 mL, 1:1, v/v) was added MS 4 Å (1 g), and the reaction mixture was allowed to stir at room temperature for 30 min under argon and cooled to −25 °C. To the cooled reaction mixture were added NIS (510 mg, 2.27 mmol) and TfOH (10 μL), and

• -O-acetyl-β-D-galactopyranoside (10): To a solution of compound 8 (800 mg, 1.23 mmol) and compound 9 (1.3 g, 1.47 mmol) in anhydrous CH2Cl2 (10 mL) was added MS 4 Å (500 mg), and the reaction mixture was stirred under argon at room temperature for 30 min and cooled to −10 °C. To the cooled reaction

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• acid, I2, Br2·SMe2 and BF3·OEt2, at temperatures ranging from rt to 80 °C. The transformations were tested under standard heating or microwave irradiation, with reaction times lasting form 30 min to 48 h. The imine 1a was generated in situ, using MS 4 Å, or previously prepared by condensation of the

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

• Haijun Qu,
• Xuejian Li,
• Fan Mo and
• Xufeng Lin

Beilstein J. Org. Chem. 2013, 9, 2846–2851, doi:10.3762/bjoc.9.320

• crystal structure of 4a. Scope of the enantioselective reaction. Reaction conditions: 5a (10 mol %, 0.02 mmol), 1 (0.2 mmol), 2 (0.2 mmol), 3 (0.3 mmol), MS 4 Å (0.1 g), toluene (1 mL), rt, 2 days. Isolated Yields were given. The ee’s were determined by chiral HPLC. Possible mechanism. Optimization of

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

• -benzylidene-2-deoxy-α-D-glucopyranoside (6): Similar as described in [21]. To a solution of compounds 2 (2 g, 5.00 mmol) and 3 (2.5 g, 5.42 mmol) in anhydrous CH2Cl2 (10 mL) was added MS 4 Å (2 g), and the reaction mixture was stirred under an argon atmosphere at room temperature for 30 min. The reaction

• ; 1:3, v/v) was added MS 4 Å (2 g), and the reaction mixture was stirred under an argon atmosphere at room temperature for 30 min. The reaction mixture was cooled to −40 °C. To the cooled reaction mixture NIS (780 mg, 3.46 mmol) and TfOH (15 μL) were added, and the mixture was stirred at same

• -benzyl-α-D-glucopyranosyl)-(1→3)-(2-O-acetyl-4-O-benzyl-α-L-rhamnopyranosyl)-(1→3)-2-azido-4,6-O-benzylidene-2-deoxy-α-D-glucopyranoside (9): Similar as described in [21]. To a solution of compounds 8 (1.5 g, 1.35 mmol) and 5 (580 mg, 1.48 mmol) in anhydrous CH2Cl2 (5 mL) was added MS 4 Å (1 g), and the

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• ) (i) TBSCl, Et3N, CH2Cl2, rt; (ii) BnBr, NaH, Bu4NI, THF, rt; (h) (i) p-TsOH, MeOH, rt; (ii) TFA, CH2Cl2, rt; (i) (i) NaIO4, Et2O/H2O (1/1), rt; (ii) PCC, MS 4 Å, CH2Cl2, rt; 17% (six steps); (j) TBSCl, imidazole, DMF; 77% (6b); or MOMCl, NaH, THF; 68% (6c); or Ac2O, DMAP, Et3N, CH2Cl2; 99% (6d