Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• . However, depending on the nature/substitution pattern of the arylboronic acid, some of the arylglycine products could only be obtained in very low enantioselectivities. This can be attributed to a fast, uncatalyzed racemic background reaction of the boronic acids, in particular for electron-rich or

• reaction (pathway A) via ate complex 11a [10] of the electron-rich, more nucleophilic (p-methoxyphenyl)boronic acid (2b), which outcompetes the palladium-catalyzed pathway B (Scheme 2b). In turn, suppression or at least a significant deceleration of the uncatalyzed background reaction should lead to an

• -arlyglycine in 30% yield and an enantiomeric ratio of 94:6. In the absence of a catalyst, the racemic product was formed in 61% yield. The comparison with the uncatalyzed reaction using free phenylboronic acid showed that the reaction of the phenyltrifluoroborate is considerably slower (61% yield after 16 h

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• alkenes under chiral BINOL-derived Brønsted acid catalysis has been studied by Houk and Rueping in 2014 [33]. These authors established the origin of the enantioselectivity and the differences between the catalyzed and uncatalyzed reactions, suggesting that the catalyzed reaction is, actually, a so-called

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• proceeded further, in uncatalyzed fashion at room temperature and yielded, after intramolecular azide–alkyne click reaction novel, structurally intriguing bistriazoles. Keywords: α-acetyl-α-diazomethane sulfonamide; intramolecular click reaction; uncatalyzed; room temperature; 1,2,3-triazoles

• benzaldehydes and propargylamines. Besides the initial formation of the triazole core, the reaction proceeded further, in uncatalyzed fashion at room temperature and yielded structurally intriguing bistriazoles whose structure was unequivocally confirmed by single-crystal X-ray analysis. Compounds are non

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• dihalogenated at the ortho and meta-position(s) relative to the electron-donating substituent, which may be attributed to competition between PdII-catalyzed reactions and uncatalyzed electrophilic substitution. Our results are consistent with those reported by Sanford's group for the halogenation of various

• product as a single isomer in both the catalyzed and uncatalyzed reactions. Neat grinding of L3 and L4 with NCS produced the monochlorinated products L3Cl-I and L4Cl-I as single isomers within one hour (Table 1, entries 2 and 3). In contrast, the reaction of L5 with NCS resulted in a mixture of mono- and

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• reaction. An uncatalyzed background reaction was not observed while performing the model reaction in toluene as a solvent at 30 °C for 24 h. To our delight, when the same reaction was carried out in presence of 5 mol % catalyst I in toluene at 30 °C for 48 h, the desired product 3a was obtained in 84

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• EDAMs (R1 ≠ R2) were also applied to check the regioselectiveness of this addition and cyclization reaction. The methodology provides a simple, straightforward, and facile path to access fully decorated 1,2,3-triazoles 25 in moderate to good yield. Noticeably, this uncatalyzed addition and cyclization

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• of our study, the Ugi products 6 were involved in IAAC. Compounds such as 6aab, 6abb and 6aeb with terminal alkyne fragment can be easily cyclized under thermal uncatalyzed conditions in various solvents – from nonpolar benzene to polar protic solvents, and even in water, depending on substrate

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• , electrophilic alkyl radicals were used in several transformations, such as electrophilic cross couplings under nickel catalysis, either with boronic acids [35] or different (aryl)halides [36][37][38]. Furthermore, visible light-promoted uncatalyzed electron transfer via the formation of electron donor–acceptor

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• rearrangements. Furthermore, these organocatalysts slowed down the Ireland–Claisen rearrangement in comparison to an uncatalyzed reaction. The catalyst-free reaction proceeded well in green solvents or without any solvent. DFT calculations showed that the activation barriers are higher for reactions involving

• . For this, we have compared the uncatalyzed Ireland–Claisen rearrangement with three hydrogen-bond-catalyzed reactions. As model H-bonding catalysts, we selected diphenylthiourea, Schreiner thiourea, and the corresponding squaramide with bis(trifluoromethyl)phenyl groups. We have evaluated both the (E

• )- and (Z)-silyl ketene acetal 2c derived from 1c as starting material for the reaction. The activation barrier for the uncatalyzed reaction of (E)-silyl ketene acetal was 98.5 kJ·mol−1, and for (Z)-silyl ketene acetal 88.7 kJ·mol−1 (Figure 2). Charges on the allylic oxygen in the reaction transition

Unexpected polymorphism during a catalyzed mechanochemical Knoevenagel condensation

• Sebastian Haferkamp,
• Andrea Paul,
• Adam A. L. Michalchuk and
• Franziska Emmerling

Beilstein J. Org. Chem. 2019, 15, 1141–1148, doi:10.3762/bjoc.15.110

• condensation in detail. Results and Discussion The catalyzed Knoevenagel condensations of mono-fluorinated benzaldehydes 1a–c with malonodinitrile (2) are depicted in Scheme 1. In contrast to previous work, which reported the uncatalyzed reaction [19], piperidine was used as a basic catalyst. This was done as

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• 01003, Ukraine A.V. Bogatsky physico-chemical institute of the National Academy of Sciences of Ukraine, 86, Lustdorfskaya doroga, 65080, Odessa, Ukraine 10.3762/bjoc.15.101 Abstract The unexpectedly uncatalyzed reaction between 2-amino-4-arylimidazoles, aromatic aldehydes and Meldrum’s acid has

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• optimizing chemoselectivity. As a model reaction, an equimolar three-component mixture of precursors 1{1}, 6{2} and 7{1} was subjected to various catalyzed and uncatalyzed conditions and the results are summarized in Table 1. Further studies showed that the Lewis acid-catalyzed reactions (Table 1, entries 3

• sodium thiosulfate to destroy the excess iodine. Finally, purification of the crude reaction mixtures by column chromatography was required in all cases. Uncatalyzed general procedure for the synthesis of products 9. An equimolar mixture of the appropriate indole 1 (1.0 equiv), aldehyde 6 (1.0 equiv

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• , entry 9). The yield decreases as the substituents become larger (Table 10, entries 6–8, 10 and 11). This trend can also be seen in the uncatalyzed reaction (Table 10, entries 13, 14). Only for 11c and silandiol 9 a considerable ee with 5% is determined (Table 10, entries 7 and 11). Chlorosilanol 8 does

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing electron-withdrawing groups. The sequence involves an initial SNAr displacement, N-acylation and MW-assisted ring closure. Remarkably, the uncatalyzed N-arylation of 2

• require in most cases either a large excess of the nucleophile [75][76][77] or Boc protection [78][79] in order to obtain the monoarylated product in acceptable yields. There are some reports on selective SNAr reactions of piperazine [80] but, to the best of our knowledge, uncatalyzed selective N

• , avoiding the use of protecting groups, and affording the desired heterocycles in good to excellent overall yields. A suitable balance between reactivity and selectivity was achieved in the SNAr reaction which, to our knowledge, is the first report on a successful uncatalyzed N-monoarylation of the

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• ) for the rate-limitting [3 + 2]-cycloaddition step leading to the 1,3-isomer was substantially lower if compared to the uncatalyzed reaction pathway (ΔG‡ = 32.5 kcal·mol−1). If other Cu(II) salts were used as a catalyst then the ratio of 1,3-/1,4-isomers gradually changed from 90:10 to 3:97 (Table 8

• . Quantum calculations [92] and IR measurements performed for Cu(OAc)2 also show that the Lewis acid character of this salt is less pronounced and formation of the 1,3-diphenylpyrazole necessitates a much higher activation free energy (ΔG‡ = 41.4 kcal·mol−1) than for the uncatalyzed reaction. Formation of

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• (monitored by 1H NMR spectroscopy, see Supporting Information File 1). Formation of triazoles 13w and 14w was unexpected, because the uncatalyzed Huisgen reaction usually requires higher temperature or activation by electron-withdrawing substituents at the alkyne or electron-donating substituents at the

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• constructed. From the slope of this plot the reaction order r of the system can be determined [28]. It should however be considered that if the uncatalyzed bimolecular pathway (r = 0) also contributes to the formation of T, the measured reaction order r reflects a weighted average of the catalyzed and

• uncatalyzed pathways and can therefore have a value smaller than 1, even for cases where the autocatalytic pathway itself would have a reaction order r = 1. In such situations computational simulations of the system can provide additional information on the replication processes that are involved [29]. 2.4

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• not present in nucleic acids [2][3][4][5]. Although Huisgen described the uncatalyzed reaction yielding 1,2,3-triazoles already in the 1960s [6], the bioorthogonality with respect to proteins and nucleic acids emerged after Sharpless [7] and Meldal [8] had reported that catalysis by Cu(I) enhances not

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• -heteroarene reactants [91]. Nicholas and co-workers investigated the thermal (uncatalyzed) and Cu(I)-catalyzed reactions of 2-nitrosopyridine with various dienes [92]. Generally, the cycloaddition of an unsymmetrical diene and nitroso compound will lead to two regioisomers – proximal and distal (Scheme 11

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

• in aprotic solvents such as THF at low temperature, and therefore the background, uncatalyzed reaction should not interfere. As shown in Table 1, the best results were achieved by using 1 equiv of zinc bromide (Table 1, entry 8), affording a 10:1 diastereomeric ratio and an excellent overall yield

A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

• Jubi John,
• Eliza Târcoveanu,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 1462–1470, doi:10.3762/bjoc.10.150

• acetoacetate. The first transformation was carried out under basic conditions (Na2CO3 (1.0 equiv), dioxane, 50 °C, 6 h) and the second under optimized conditions. Both reactions afforded the Mannich addition product in similar yields, proving that Mannich addition was uncatalyzed. Based on these results, we

• uncatalyzed pathway. The second step of the catalyzed route involves the oxidative addition of Pd(0)Ln to the C–Cl bond of Mannich adduct 16 to form 17. The oxy-π-allylpalladium intermediate 18 can then be formed from intermediate 17 [4][5][6][7][8]. The final step of the catalyzed mechanism, i.e., the ring

Substrate dependent reaction channels of the Wolff–Kishner reduction reaction: A theoretical study

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 259–270, doi:10.3762/bjoc.10.21

• uncatalyzed (without base) Knoevenagel condensation in water. Experimental conditions and yields are taken from a) ref. [13] and b) ref. [14], respectively. Reaction models of neutral (a) and anionic (b) systems. Water molecules are linked to oxygen lone-pair orbitals and to H–N bonds of hydrazine. In the

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• pheromone 20 upon enzyme catalyzed fragmentation. Uncatalyzed DVCPR takes places to give 21 within short periods of time. The corresponding activation energies have been determined as well as the half-lifes at different temperatures. Bioassays proved that 20 was far more bioactive than 21, and since the