Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• proton in the C-α position, which leads to a stable carbanion with even mild bases, that can promote intramolecular cyclization. For example, Flores-Constante et al. [106] and Nechaev et al. [107] synthesized Ugi adducts with a propargyl group that could be used as a Michael acceptor (48–50, Scheme 44

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• -protected Michael acceptor, derived from proline, allowed for preparation of compound 27 with a 35% yield in 4 hours without control of diastereoselectivity (dr = 1:1). Finally, to prove that the optimized reaction also works at a larger scale, the model reaction was carried out on a 2.2 mmol scale (Figure

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• originating from unique fluorine atoms or fluorinated groups [1][2][3][4][5][6][7]. During our study in this area, ethyl 4,4,4-trifluorobut-2-enoate (1a) has been frequently employed as a potent and convenient Michael acceptor towards a variety of enolates [8][9][10][11][12][13][14][15] as well as

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

• stabilized by an intramolecular hydrogen bond with a protonated amine unit activates the Michael acceptor (Scheme 4). Moreover, a strong but reversible covalent bond locates the electrophile upon the quinoline unit of the catalyst and thus subsequently blocks the bottom approach of the thiomalonate. Hence

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

• reactions, especially as a Michael donor at the central methylene carbon, and Michael acceptor at the enone vinyl carbon. Therefore, it would be interesting to develop novel methodologies using curcumin and its non-natural analogs as key starting materials [24]. Because of its multifaceted reactive site

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

• incorporated into the second isocyanides. The utility of this protocol was evaluated by conducting a gram-scale synthesis using 10 mmol of all precursors and there was no significant reduction in the yield of products. Al-Tel et al. [62] developed a synthetic strategy where a Michael acceptor (a conjugated

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• -based activator. The deoxyalkylation was performed by initially stirring the alcohol substrate with NHC and pyridine in MTBE for 15 min. After that, Michael acceptor, sodium acetate, 1,1,3,3-tetramethylguanidine, and [Ir(III)] photocatalyst in MTBE/DMA were added to the mixture. Then, blue LEDs were

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

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• reactive in chloroform solution, while in methanol the corresponding phosphonium phenolate is formed. Keywords: Lewis-base catalysis; Michael acceptor reactivity; phospha-Michael reaction; phosphonium phenolate zwitterion; Introduction Organocatalysis has emerged in recent years as a valuable and

• purified by recrystallization whereby the solvents used vary depending on the parent Michael acceptor (for details, see Supporting Information File 1). Yields are not optimized and given in Table 1. The synthesized zwitterions were investigated via 1H, 13C and 31P NMR spectroscopy. All synthesized

• compounds share a characteristic doublet of doublet pattern centered in the range of 6.21 to 6.09 ppm depending on the Michael acceptor used. This signal is attributed to the aromatic proton in position 5 of the 2,4-di-tert-butylphenol substituent that experiences a meta-coupling to the aromatic proton on

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• Michael acceptor unit. They have found application as valuable synthons and useful precursors for the synthesis of various biologically active molecules [1][2][3]. Recently, MBH adducts, as electrophilic substrates, have been employed to achieve fruitful results in allylic substitution reactions with

• alcohols 4, such as 4a, starts with a conjugate addition of imidazole (2a) at the C-β position of the Michael acceptor 4a, followed by elimination of the hydroxy moiety, affording the intermediate I. Similarly, a further second β’-conjugate addition of imidazole (2a) to I might occur, followed by

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• activation of the Michael acceptor and the formation of intermediate organocuprates from stoichiometric organometallic reagents [18]. Metal enolates formed in this way can react in many transformations (Scheme 1) [19][20]. It has been documented that metal enolates from conjugate additions engaged in aldol

• acryloyloxazolidinone 183, the reaction gave the expected aldol product 184 in good yields and diastereomeric ratios with a preference toward the syn-adduct (Scheme 47A). Interestingly, when they used methacryloyloxazolidinone 185 as a Michael acceptor, the X-ray analysis of the product showed a rearranged structure

• activation of aryl pyrazoles, followed by the asymmetric conjugate addition to the Michael acceptor. Then, the formed cobalt enolate participates in the intermolecular aldol reaction with an aldehyde 207. The stereochemistry of this tandem procedure is controlled by the chiral Co(III) complex C4 bearing

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• Michael acceptor. A number of thiols was taken as the model compounds. The reaction was performed under thermodynamic conditions reported in [41], to compare the thermodynamically controlled stereoselectivity of L7 and L1. The use of a 2 molar excess of K2CO3 induces the equilibrium between the isomers

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• ) dimerization has some limitations, such as its controlling selectivity for intermolecular reactions in differently activated alkenes, and low reactivity. Han and co-workers [6] addressed the latter one by designing a substrate in which nucleophile functionality is also present in the Michael acceptor to

• accelerate the reaction. In conventional intermolecular RC reactions, the reaction proceeds by the intermolecular addition of a nucleophilic catalyst to the enone substrate to generate an enolate in the first step. In the second step the enolate ion attacks the other Michael acceptor at β-position in an

• products (±)-incarvilleatone (1) and (±)-incarviditone (2) could be obtained from the RC product 4 by using oxa-Michael and aldol reactions [3][4]. The RC product 4 in turn can be obtained from a monomeric Michael acceptor, i.e., (±)-rengyolone (3). The Michael acceptor for the intermolecular Rauhut

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• later revised as that of (Z)-4. The same compound is also observed in S. olivaceus [10] and was reported to function as a competitive inhibitor of glutathione S-transferase [11], which may be a result of a thiol addition of glutathione to the Michael acceptor in 4. While the relative and absolute

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• colleagues reported in 2000 that the reaction between a Michael acceptor such as diethyl fumarate and a sulfur-ylide, prepared from ethyl 2-diazoacetate and tetrahydro-2H-thiopyran in the presence of Cu(acac)2, yielded triethyl cyclopropane-1,2,3-tricarboxylate in 68% yield (Scheme 1, reaction 1) [10]. The

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• derivatives were synthesized on the basis of Michael acceptor ability of 3-alkylidene oxindoles with various donor synthons [16][17][18][19][20][21][22]. However, in spite of the progress in the synthesis of dispirocyclopentanebisoxindoles with concise structural and stereochemical diversity, the one-pot

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• -protecting group and electron-withdrawing properties of the protection groups are essential for coordination with the catalyst and for the reactivity of the Michael acceptor. Using a tosyl-protected oxindole the reaction was sluggish, the yield was low and the enantioselectivity could not be determined

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• powerful nitrogen source for the synthesis of various N-heterocycles, such as isoquinolines, quinolines, pyridines, pyrroles, indoles, azoles, and azepines [40][41][42][43][44][45]. 1,3-Enyne, as a powerful Michael acceptor, is a wonderful synthon for the synthesis of N-heterocycles via tandem addition and

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• peptide, which can be further utilized as a Michael acceptor for a variety of nucleophiles. Based on their manganese-catalyzed allylation using Morita–Baylis–Hillman carbonates, the Ackermann group established an applicable late-stage C–H glycosylation of peptides (Scheme 12) [95]. Thus, allylative

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• more electron-rich catalysts is less pronounced. The experimental activity trend was rationalized by calculating the Michael acceptor affinities of all phosphine–Michael acceptor combinations. Besides this parameter, the acidity of the alcohol has a strong impact on the reaction speed. The oxidation

• masses of about 1200 g/mol at room temperature are accessible. Polymerizations carried out at 80 °C resulted in macromolecules containing a considerable share of Rauhut–Currier-type repeat units and consequently lower molar masses were obtained. Keywords: Michael acceptor affinity; Michael addition

• formed by the conjugate addition of the phosphine to the Michael acceptor, is believed to be protonated by the alcohol forming the actual catalytically active species namely ion pair ii, consisting of a phosphonium cation and an alkoxide. The alkoxide in ii then reacts with another electrophile

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• (Scheme 20). It is important to highlight that cyclization occurred without epimerization with such as strong base. Isoindolines with substituents at 1 and 3 positions were synthesized from an aromatic N-tert-butanesulfinyl imine 67, bearing a Michael acceptor in the ortho-position. Fustero, Barrio and co

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• ]. Compound 17 can be transformed into the coenzyme A thioester 18 by the CoA ligase DmdB, followed by FAD-dependent oxidation to the α,β-unsaturated compound 19 by DmdC. The attack of water to the Michael acceptor catalyzed by the enoyl-CoA hydratase DmdD yields the hemithioacetal 20 that spontaneously

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• system was tested (Scheme 5, method 2). A stream (0.15 mL/min) containing the carbamate product (0.5 M DCM, 1.0 equiv), the Michael acceptor (1.2 equiv), and tetrabutylammonium bromide (TBAB, 0.1 equiv) [29] was thereby mixed in a T-piece with a stream of aqueous KOH (50 wt %, 0.15 mL/min) creating a

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• as a Michael acceptor. Stronger bases, such as NaH and t-BuOK seemed to be preferable (Table 2, entries 3 and 6), and amines such as DBU and 1,1,3,3-tetramethylguanidine (TMG) were found to be insufficient (Table 2, entries 10 and 11). Judging from the possible mechanism, this process was considered