Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• polyfunctional precursors 1, 2, and 3, two pathways are theoretically possible (Scheme 2 and Scheme 3). The first one involves the N-nucleophilic Michael addition to the activated multiple bond of the imide, leading to the formation of linear intermediates 6 or 8 (pathways A1 and B1) at the expense of the endo

• 6a, which undergoes subsequent cyclization steps more favorably, leading to the formation of the target product 4a (∆G = −3.02 kcal/mol). This suggests that the first step of intermediate formation is the critical one. It is also noteworthy that the Michael addition via intermediate 6a is an

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• novel lipophilic cinchona squaramide organocatalyst. This organocatalyst was evaluated in a benchmark Michael addition of acetylacetone to trans-β-nitrostyrene, yielding the Michael adduct with high yield and enantioselectivity. The hydrophobic chain of the catalyst allowed the organocatalyst to be

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• , imidazole, thiadiazole, or other fragments [44][45][46][47][48]. Previously, we obtained a series of sterically hindered catechols linked through a sulfide bridge with various polar or low-polar groups [36][49][50][51] and heterocyclic fragments [52] via the Michael addition reaction. Also, we have

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• proved ineffective in facilitating the Michael addition of bisthiomalonates to conjugated ketones, whereas DABCO enabled the formation of desired products under mild conditions [30]. However, reports of highly stereoselective protocols utilizing hydrogen bonding catalysis have mainly focused on

• -chlorobenzylideneacetone (E5). In contrast to previous examples, where the use of 1.5 equiv of the electrophile was a necessary step to ensure product formation in a ball mill (see Schemes 2–4), an equimolar mixture of acceptor E5 and nucleophile 1–4 was subjected to Michael addition reaction using system A (Scheme 6

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• carbocation of I produces intermediate II, which converts into intermediate III through a deprotonation–protonation process. Finally, the elimination of PhNH2 from intermediate III occurs to afford the desired product 2a. In the presence of NaOH, the Michael addition between 1a and base initially occurs to

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• spaces. The confinement of the heterogeneous version of cinchona amine and thiourea catalysts was reported, leading to improved enantioselectivity values in the Michael addition of nitromethane (5) to chalcone (6) through modification of the pore size of mesoporous silica 8 or 9 (Scheme 2) [63]. Thus

• lead to a decrease in selectivity. Connon and co-workers have attached a cinchona thiourea organocatalyst to magnetic nanoparticles 13 for the Michael addition of dimethyl malonate (10) to trans-β-nitrostyrene (11) (Scheme 3) [31]. To explore the potential impact of nanoparticles on catalyst efficiency

• organocatalyst. To validate this hypothesis, the Michael addition was repeated in the presence of both unsupported thiourea 14 and the nanoparticles. The resulting product was isolated with only 84% ee, indicating that the nanoparticles compete with the thiourea catalyst 14 for the substrate under these

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

• regioselectivity, with 3,4-fused pyrazoles being accessible when cyclic β-oxodithioesters are employed as substrates. However, aromatic amines cannot be successfully employed in the sequence. Alkenoyl derivatives as key intermediates The Michael addition and cyclocondensation of hydrazines and α,β-unsaturated

• phosphane ligands is crucial for the selectivity in this reaction. Suzuki coupling can also serve for the functionalization of iodochromones 55, which, as α,β-unsaturated ketones, undergo ring opening under the reaction conditions, followed by Michael addition–cyclocondensation. Xie et al. devised a method

• hindrances. α,β-Unsaturated ketones embedded and tethered in chromene systems 58 were successfully employed in a pseudo-five-component reaction with hydrazine in boiling acetic acid to give the corresponding 4-acylpyrazolinylpyrazoles 59 (Scheme 17) [76]. The Michael addition–cyclocondensation of the α,β

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• double Michael addition of γ,δ-unsaturated-β-keto esters or Nazarov reagents with suitable acceptors such as nitroalkenes or alkylideneazalactones [7][8][9][10]. From the perspective of an active methylene containing organic moiety, curcumin and its analogs serve as inexpensive and readily available

• , curcumin showcases its Michael donor–acceptor ability in different ways, such as simple Michael addition, [4 + 2] annulation, Michael addition followed by cyclization or one-pot multicomponent reactions (MCR), etc. (Scheme 1) [25]. In 2011, our group reported the reactivity of curcumin as a Michael donor

• –acceptor with nitroalkenes, resulting in multi-substituted cyclohexanones through a cascade inter–intramolecular double Michael addition process with high diastereoselectivity [26][27]. Subsequently, the enantioselective versions of the above reaction and a similar diastereoselective cascade Michael

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• aza-Michael addition, leading to the benzoxazepinium triflate salt 89. To broaden the scope of the reaction, 2-aminopyrazine and 2-aminoquinoline were also introduced to the one-pot process, furnishing 6-7-5-6 and 6-7-5-6-6 polycycles, respectively (not shown). Chen et al. [63] developed an

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• dearomatization of 33 via enantioselective hydroxylation using molecular oxygen and generates cyclohexadienone 34. As demonstrated by Corey [36] and Nicolaou [37], highly reactive intermediate 34 likely dimerizes non-enzymatically through stepwise reactions involving (1) an initial intermolecular Michael addition

• synthesized 33 generated the highly reactive intermediate 34 in aqueous solvents under mild conditions [37][42]. In this process, the co-solvent (cs) allowed control of the dimerization modes via either Michael addition or Diels–Alder reactions, facilitating the systematic total synthesis of the

• experimental results, Gulder and co-workers devised a strategy to control the dimerization modes by adjusting the polarity of the organic co-solvent to establish the divergent synthesis of dimeric scaffolds. Indeed, with 20% DMF in the SorbC-catalyzed enzymatic oxidative dearomatization, the Michael addition

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• structurally diverse pyrazole derivatives [4][5][6][7][10][11][12]. 4-Unsubstituted pyrazolin-5-ones are well known precursors for the construction of optically active structurally diverse pyrazoles [10][11][12]. In this context, the organocatalyzed asymmetric Michael addition of 4-unsubstituted pyrazolin-5

• who reported a chiral amine-catalysed aza-Michael addition reaction of pyrazolin-5-ones with α,β-unsaturated ketones to access β-(3-hydroxypyrazol-1-yl)ketones (Scheme 1a) [22]. The developed reaction was restricted to α,β-unsaturated ketones with aliphatic substituents (Scheme 1a) [22]. Ji and Wang

• disclosed organocatalyzed [5 + 1] double Michael additions between pyrazolones and dienones (Scheme 1b) [23]. Very recently, the Chimni group reported a cinchona-derived squaramide-catalyzed 1,4-Michael addition reaction of pyrazolin-5-ones with 2-enoylpyridines (Scheme 1c) [24]. Recently, we developed an

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

• enabling the activation of small yet highly relevant organic substrates. For example, Huber and co-authors recently designed a Te-based catalyst in an indole Michael addition reaction [1][2][3][4][5]. Pale and Mamane utilized another Te-based catalyst in an electrophilic bromine-mediated cyclization

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• has become one of the most popular route for the site-selective modification of cysteine residues in bioconjugation technology. We suppose that the maleimide group in porphyrin 11 is a useful target for thiol conjugation via Michael addition reactions [44]. This also concerns biotin-conjugated organic

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• synthesis of spiro-annulated pyrrolidine-2,5-diones by catalyzed spirocyclizations involving aldehydes [11], tetrahydrofuran [12][13], and in the O–H insertion/Claisen rearrangement/intramolecular oxa-Michael addition cascade [14] (Scheme 1). Herein, we report our findings obtained, while investigating the

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• groups as measured by rates of Michael addition [52]. This suggests that in fact nitrogen nucleophilicity alone is not the most relevant factor since sulfonamides react much slower in hydroamination. Sulfonamide N–H bonds are significantly more acidic than urea, amide and carbamate N–H bonds (16.1 versus

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• ][12]. At the first stage, this reaction follows one of three possible reaction pathways, including Schiff base formation (attack at the C(3) center), Michael addition at C(1), or nucleophilic substitution (SNH) at the C(2) center [13][14][15]. Most readily used is the pathway involving carbonyl–amine

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• , entry 3); thus, the phosphate base plays a crucial role in N-alkylation, while its basicity is insufficient to promote aza-Michael addition (pKa of the conjugate acid of the phosphate base is 1.72 in H2O) [12]. Furthermore, N-alkylation proceeded in a divided cell (anodic chamber); thus, the possibility

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• methacrylamide group. Detritylation was not carried out in the last synthetic cycle, which would otherwise remove the polymerizable tag. A portion of the CPG was subsequently subjected to deprotection and cleavage. To prevent the potential Michael addition side reaction of acrylonitrile to nucleobases, the 2

• -cyanoethyl groups were removed by flushing the CPG with a solution of DBU in ACN. Under these conditions, the ODN remains on CPG and the nucleobases remain protected, both of which decrease the probability of the Michael addition side reaction. After washing off acrylonitrile, the CPG was subjected to

• failure sequences 4 and other impurities were then washed away using aqueous solutions including mildly basic solutions. These washes might also remove N,N-dimethylacrylamide added to ODNs via Michael addition. The full-length ODN 6 was cleaved from the polyacrylamide gel (5) using 80% acetic acid (Scheme

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• ylide B. Thirdly, the intermediate C is formed by the nucleophilic substitution of a halide ion in substrate 1 by the allylic ylide B. Then, Michael addition of the amino group to the C=C bond results in the cyclic intermediate D. Finally, the spiro[indoline-3,5'-[1,2]diazepine] 3 is produced by the

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

• , application, and recycling of a new lipophilic cinchona squaramide organocatalyst. The synthesized lipophilic organocatalyst was applied in Michael additions. The catalyst was utilized to promote the Michael addition of cyclohexyl Meldrum’s acid to 4-chloro-trans-β-nitrostyrene (quantitative yield, up to 96

• lipophilic organocatalyst 2 (Scheme 2). Application and recycling of the lipophilic cinchona-squaramide organocatalyst in the stereoselective Michael addition To prove that the previously applied catalytic unit kept its activity, the lipophilic organocatalyst 2 was applied in the stereoselective Michael

• chosen as a precipitating solvent for the catalyst recycling. To investigate the solvent effect, the stereoselective Michael addition reaction was carried out in those solvents that dissolved the catalyst and from which the catalyst was successfully precipitated by adding methanol. Furthermore, a

Synthesis of 7-azabicyclo[4.3.1]decane ring systems from tricarbonyl(tropone)iron via intramolecular Heck reactions

• Aaron H. Shoemaker,
• Elizabeth A. Foker,
• Elena P. Uttaro,
• Sarah K. Beitel and
• Daniel R. Griffith

Beilstein J. Org. Chem. 2023, 19, 1615–1619, doi:10.3762/bjoc.19.118

• number of alkaloid natural products can be accessed from commercially available tropone in as little as five steps: 1) formation of tricarbonyl(tropone)iron, 2) aza-Michael addition, 3) amine protection, 4) photodemetallation, and 5) intramolecular Heck reaction (two steps – aza-Michael addition and

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• of the phthalimide anion to the β-carbon of chalcone, followed by electrophilic sulfur attack and deprotonation. In the thiolation, in situ formation of thiophenol occurred, followed by thio-Michael addition of chalcone with thiophenol. N-Calcogenophthalimide also can be used to prepare

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96