Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• benzodiazepine with different bases (caesium carbonate, sodium hydroxide). However, the complete cyclisation to the pyrrolobenzodiazepinone was not achieved, so the described three-step strategy starting from 2-nitrobenzoic acid (Ugi reaction/cyclization to pyrrolidine/reduction sequence) remains as a better

• after the Ugi/cyclization sequence, yielded the corresponding piperazinoquinazoline 14 with a high global yield (Scheme 10). Moreover, the treatment of piperazinones 9c–e,k derived from 3-bromopropanamine with caesium carbonate in boiling acetonitrile for 1 h afforded the corresponding

• , without purification, was treated with caesium carbonate (1 equiv) and heated to reflux for an hour. Gratefully, the dipyrrolopiperazinone derivatives 12 were obtained with high yields and complete diastereoselectivity in an efficient and simple way (Scheme 11, Table 6). The structure of these systems was

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• dissolve caesium fluorides and facilitate an electrochemical benzylic C(sp3)–H fluorination of triphenylmethane (Figure 39) [97]. The authors suggested that PEG complexed the metal ion, increasing the nucleophilicity of the fluoride ion. Product 23 was achieved in 85% isolated yield after a small

• optimisation campaign. The fluorinated alcohol HFIP was used to dissolve caesium fluoride allowing for the electrochemical benzylic fluorination by Fuchigami, Inagi and co-workers in 2021 (Figure 40) [98]. The HFIP/CsF system functioned as both a fluoride source and as supporting electrolyte, enabling the

• PEG and CsF. Electrochemical benzylic C(sp3)–H fluorination with caesium fluoride and fluorinated alcohol HFIP. Electrochemical secondary and tertiary benzylic C(sp3)–H fluorination. GF = graphite felt. DCE = 1,2-dichloroethane. Electrochemical primary benzylic C(sp3)–H fluorination of electron-poor

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• ) gave only relatively low conversions to 2a and 3a. Other organic nitrogen bases were tested, and we found that quinuclidine (entries 8 and 9, Table 1) gave high conversion to difluorinated product 3a, with very little monofluorinated product 2a being observed. Suspensions of caesium carbonate or sodium

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• 6 (732 mg, 1.19 mmol) was dissolved in DMF (15 mL), and caesium carbonate (1.75 g, 5.37 mmol, 4.5 equiv) was added to the solution at 0 °C. The reaction mixture was stirred for 20 min at this temperature. Then, the DMF (10 mL) solution of tosylated N-Boc-protected ethanolamine (955 mg, 3.03 mmol

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• included the binding of caesium cation in the oxygen-rich crown ether segment, with the fluoride interacting with NH of calix[4]pyrrole. Additionally, receptor 5 formed an unprecedented 2:2 complex with CsCl, which included two different ion-pair binding sites, whereas with the addition of CsNO3, a 1:1

• complex was created, where both ions were held in close proximity. It was further reported that 5 could adapt its binding behaviour depending on the counteranion in the caesium salt. Later Sessler and co-workers used naphthocrown-strapped calix[4]pyrrole 6 as a host to entrap CsF or CsCl ion pairs [103

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• 3,4-dihydropyran in dimethylformamide to obtain the corresponding tetrahydropyranyl-protected amine 17. Subsequently, a copper-catalyzed C–O bond formation at C6 using benzyl alcohol in the presence of caesium carbonate, copper(I) iodide, and 1,10-phenanthroline furnished benzyl ether 18 in excellent

• -(tetrahydro-2H-pyran-2-yl)-1-deazapurine (18) Compound 17 (1.72 g, 5.23 mmol), copper(I) iodide (CuI, 99.52 mg, 0.52 mmol), 1,10-phenanthroline (188.35 mg, 1.05 mmol), caesium carbonate (Cs2CO3, 2.38 g, 7.32 mmol) and benzyl alcohol (BnOH, 1.13 g, 1.07 mL, 10.45 mmol) were suspended in 2.62 mL toluene (0.5 mL

• )), 154.08 (H-C(2)), 162.52 (H-C(6)); ESIMS (m/z): [M + H]+ calcd for 151.06; found, 151.06. O6-Benzyl-1-deazahypoxanthine (31) Compound 17 (500 mg, 1.52 mmol), copper(I) iodide (CuI, 28.93 mg, 152 µmol), 1,10-phenanthroline (54.75 mg, 304 µmol), caesium carbonate (Cs2CO3, 692.93 mg, 2.13 mmol) and benzyl

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• 206.6, 154.9, 85.1, 82.3, 59.0, 45.0, 36.5, 32.2, 28.4, 18.1, 12.1 ppm; HRMS (m/z): [M + Na]+ calcd 424.2490; found, 424.2480; [α]D20 +37.4 (c 0.5, CH2Cl2). (5S,6R)-5-Ethyl-6-ethynyl-5,6-dihydro-2H-pyran-2-one (21): Caesium fluoride (290 mg, 1.91 mmol, 1.3 equiv) was added to a solution of the lactone

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

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• observed, which served as a basis for further optimization. Variation of the base showed caesium carbonate to be significantly more effective than the organic bases examined, giving 88% conversion to product 6 (Table 1, entries 2 and 3). Trialling a number of alternative solvents, including dichloromethane

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• strategies have also been described using the hydroxylamine scaffold, affording an efficient and general access to iminyl radicals. The first reports were released simultaneously by Leonori and Studer (Scheme 28) [141][142]. α-N-Oxy acid 28.1 carboxylates (Eox = +1.6 V vs SCE for the caesium carboxylate) can

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• (R = Me, iPr and Ph) in benzene produced chiral acetal 22. Subsequent palladium-catalyzed C–C coupling of the acetal with 4-fluorophenylboronic acid (FPBA) in the presence of caesium carbonate and tri-tert-butylphosphine afforded aryl fluorides 23. Pure ligands 24 (63–72%) were obtained by

Halide metathesis in overdrive: mechanochemical synthesis of a heterometallic group 1 allyl complex

• Ross F. Koby,
• Nicholas R. Rightmire,
• Nathan D. Schley,
• Timothy P. Hanusa and
• William W. Brennessel

Beilstein J. Org. Chem. 2019, 15, 1856–1863, doi:10.3762/bjoc.15.181

• ]∞, enable an otherwise unfavorable halide metathesis to proceed with mechanochemical assistance. From this result, we demonstrate that ball milling and unexpected solid-state effects can permit seemingly unfavored reactions to occur. Keywords: caesium; entropy; intermolecular forces; mechanochemistry

• difficult, and the extent of even partial exchange is hard to predict. For the alkali metals, all electronegativity scales indicate that caesium is the most electropositive, but they also indicate that there is comparatively little variation in this metric [12]. What happens when the energy difference

• likely to be isolated. The high concentration of reagents in a solid-state reaction may influence product formation as well. The possibility of partial exchange also needs to be considered. If the caesium iodide were insufficiently reactive, a starting ratio of 3:1 for [KA']:CsI could give rise to

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• isocyanide component under air. In the case of using other bases, such as caesium carbonate (Cs2CO3), diisopropylethylamine (DIPEA) or sodium ethoxide (NaOEt), only the isothiocyanate intermediate of the reaction was isolated (Table 1, entries 17, 18, and 20). However, using diazabicycloundecene (DBU) as the

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• of 9, followed by an intramolecular cyclic amide formation, would produce isoindolinone derivatives 4. Employing benzoic acids 10 ortho-substituted with iodine along with alkynylcarboxylic acids 11 and ammonium acetate (12), in the presence of caesium carbonate and copper iodide as catalyst (10%), a

• reaction of propiolic acid and aryl halides [78]. Furthermore, the authors have been able to carry out the reaction in a sequential manner starting from propiolic acid and aryl iodides in the presence of caesium carbonate and a palladium catalyst. Next, addition of 2-iodobenzoic acid and ammonium acetate

Liquid-assisted grinding and ion pairing regulates percentage conversion and diastereoselectivity of the Wittig reaction under mechanochemical conditions

• Kendra Leahy Denlinger,
• Lianna Ortiz-Trankina,
• Preston Carr,
• Kingsley Benson,
• Daniel C. Waddell and
• James Mack

Beilstein J. Org. Chem. 2018, 14, 688–696, doi:10.3762/bjoc.14.57

• identifying the caesium–bromine pair was optimal for the conversion, caesium carbonate was the base of choice for the described stepwise study with ethanol. Tuning liquid-assisted grinding with ethanol Because using ethanol (high dielectric constant) as the LAG solvent afforded the highest conversion to

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• conditions were not suitable for aliphatic alkynes as they do not undergo oxidative addition with the [NiI] sulfide complex. Miyake and co-workers described a very different approach for the C–S cross-coupling between aryl thiols and aryl halides (Scheme 24) [59]. In a mixture with caesium carbonate as a

• photocatalyst was accomplished in the presence of methanol under basic conditions. For a better handling of volatile CS2, they converted it into the corresponding caesium methyl xanthate prior to the photocatalytic reaction. Photoexcited Eosin Y is quenched reductively by caesium methyl xanthate, yielding the

Curcuminoid–BF₂ complexes: Synthesis, fluorescence and optimization of BF₂ group cleavage

• Henning Weiss,
• Jeannine Reichel,
• Helmar Görls,
• Kilian Rolf Anton Schneider,
• Mathias Micheel,
• Michael Pröhl,
• Michael Gottschaldt,
• Benjamin Dietzek and
• Wolfgang Weigand

Beilstein J. Org. Chem. 2017, 13, 2264–2272, doi:10.3762/bjoc.13.223

• DMF or 5-chloropent-1-yne in dry acetonitrile. As bases we used potassium carbonate for the propargyl ethers and caesium carbonate for the ethers with the longer side chains. Aqueous work-up achieved the aldehydes in excellent yields of up to 98%. NMR spectroscopic results were found to be in good

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• -selective organocatalysts. We prepared two known carbamoyl sulfones 1 [30][31] and transformed them without isolation of intermediates into a series of five Boc-protected β-aminoalcohols 4a–e (Scheme 2). Using caesium carbonate, carbamoyl sulfones were converted into the corresponding N-Boc-protected imines

An efficient synthesis of N-substituted 3-nitrothiophen-2-amines

• Sundaravel Vivek Kumar,
• Shanmugam Muthusubramanian,
• J. Carlos Menéndez and
• Subbu Perumal

Beilstein J. Org. Chem. 2015, 11, 1707–1712, doi:10.3762/bjoc.11.185

• , entry 5), pyridine (Table 1, entry 6), N,N-dimethylaminopyridine (DMAP, Table 1, entry 7), piperidine (Table 1, entry 8), L-proline (Table 1, entry 9), potassium carbonate (Table 1, entry 10), sodium carbonate (Table 1, entry 11) and caesium carbonate (Table 1, entry 12). After identifying potassium

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• pyrrole and indole substrates 1 and 2, the unsubstituted azoles were reacted with aryl and heteroaryl iodides under copper catalysis. As far as the derivatives 1a,b, 1d,e and 2a–e are concerned, the reactions were carried out by using 1.5 equiv of the azole, 0.2 equiv of copper, 2 equiv of caesium

• reacted with 2 equiv of imidazole in the presence of 0.1 equiv of copper(I) oxide, 2 equiv of caesium carbonate as the base in dimethylsulfoxide (DMSO) at 110 °C [47]. Under these conditions, the imidazole-substituted compounds 5b, 5d and 6d were generated in 85, 67 and 40% yield, respectively (Scheme 8

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

• cyclopropane derivatives 30 (62%) and 32 (44%). Later, Michael addition in the presence of caesium fluoride and benzyltriethylammonium chloride in DMF gave the benzannulated cyclodecanone derivatives 31 (11%) and 33 (10%) (Scheme 2). Oxymercuration – Hantzsch pyridine synthesis: Kondo and Miyake [86] have

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• a common, protected MPTTF intermediate, such as 4a, 4b or 4e, in large quantities, particularly in light of the good stability of the cyanoethyl and tosyl protecting groups. As a simple example of this protocol, it has previously been shown that caesium hydroxide monohydrate (CsOH·H2O) and methyl

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• L8 (Figure 2) led to the full conversion to 1a (Table 1, entry 7). Caesium carbonate was the optimal base as neither K2CO3 nor K3PO4 gave satisfactory results (Table 1, entries 8 and 9). From the above-mentioned facts, summarized in Table 1, it follows that the optimal results were obtained using

• catalytic systems Pd2(dba)3/L1 (Table 1, entry 3) or CuI/L8 (Table 1, entry 7) in toluene with caesium carbonate as the base. We further preferred the first one (Table 1, entry 3) both due to the lower amount of the catalyst and shorter reaction time. Nevertheless, the copper-mediated variant could be

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• through sonication for 30 min at room temperature and then transferred to a septum-equipped flask which contained predried molecular sieves and caesium carbonate under an inert atmosphere. The flask was then plunged into a preheated oil bath (strictly 85–88 °C) and stirred for 30 min, followed by the