Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• between 80 and 81 gave diester 82. Through a ten-step sequence including an aza-Michael reaction, diester 82 was converted into diketone 83, which was further transformed into (−)-petrosin (84) via RCM reaction and hydrogenation. For the synthesis of (+)-petrosin (86) (Scheme 13b), a similar strategy was

• 226. Regioselective hydrolysis of 226 with TFA yielded a dihydropyran intermediate, which was benzylated to deliver 227. Desilylation of 227 gave diol 228, which underwent intramolecular Michael reaction to form bicyclic compound 230 as a single stereoisomer (87% yield over two steps). This scaffold

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• -bromochromones via a Michael reaction of an amine with an electron-deficient alkene moiety and subsequent photocatalyzed debromination. With this dual catalytic system, a range of structurally diverse enaminone derivatives have been achieved in good yields with total trans selectivity. Mechanistic studies

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• analogy with an aza-Michael reaction first with the addition of iminoiodinane accompanied with reorganization of double bonds including attack of the negatively charged sulfur atom on nitrogen with subsequent elimination of iodobenzene as good leaving group. The diversity of the structure of the target

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

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

Beilstein J. Org. Chem. 2025, 21, 1170–1170, doi:10.3762/bjoc.21.93

• Deepa Nair Abhishek Tiwari Banamali Laha Lakshminarayana Satham Irishi N. N. Namboothiri Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India 10.3762/bjoc.21.93 Keywords: arylidenemalonates; curcumins; cyclohexanones; diastereoselective synthesis; Michael

• reaction; tetrahydrochromenones; Lakshminarayana Satham is acknowledged as additional co-author of our original publication. It was subsequently determined that Lakshminarayana Satham made significant contributions to the published research. The Funding section is updated as follows: DN thanks UGC India

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• low catalyst loadings and mild reaction conditions. This research focuses on the kinetic resolution of 1,5-dicarbonyl compounds using a retro-Michael reaction, co-catalyzed at room temperature with 20 mol % of the Jørgensen–Hayashi catalyst and PNBA. The study highlights the importance of conducting

• racemization when treated with inorganic bases [25], which had led us to check the equilibrium between Michael and the retro-Michael reaction (Scheme 1). These observations have prompted us to conduct further research into this reaction for potential applications in the kinetic resolution of these adducts. In

• catalyst or the bistrifluoromethyl-substituted analog B could enable the retro-Michael reaction of only one enantiomer of the racemic mixture, potentially leading to a kinetic resolution of the 1,5-dicarbonyl compounds (Scheme 2). Results and Discussion An initial attempt was made to determine if the retro

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• azadiene in a stepwise mechanism: firstly, the vinylogous Michael addition of the dienolate to the double bond of the α,β-unsaturated N-sulfonylimine occurs in a stereoselective fashion. Subsequently, cyclization due to an intramolecular aza-Michael reaction and protonation leads to the enantioenriched

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• series of new α,β-unsaturated amides, both fluorinated and nonfluorinated, were synthesized. Keywords: gem-difluorovinyl Michael acceptors; Michael addition; trifluorovinyl Michael acceptors; α,β-unsaturated amides; Introduction The Michael reaction, characterized by the addition of stable carbon

• scope, we observed that gem-difluoroalkenes produced β-fluoro-unsaturated amides 11a–d (Scheme 3). In these reactions, we used conditions previously optimised for derivatives 1a–d (n-BuLi 4 equiv, THF, −78 °C, 3 h). The amides 11a–d preferred HF elimination over engaging in another Michael reaction

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• base-mediated deprotonation of substrates 86 produces the corresponding ester enolate. This enolate undergoes a retro-Michael reaction, generating sulfenate anion A. The sulfenate anion A then nucleophilically attacks the diaryliodonium salts 16, forming hypervalent iodine intermediates B. Finally

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

• -triazole, thiazole, or pyridine were synthesized by the reaction of 3,5-di-tert-butyl-o-benzoquinone or 3,5-di-tert-butyl-6-methoxymethylcatechol with different heterocyclic thiols. The S-functionalized catechols were prepared by the Michael reaction from 3,5-di-tert-butyl-o-benzoquinone and the

• derivatives are used as ligands in the synthesis of metal complexes (Ni(II), Pd(II), Pt(II), Cu(I), Ag(I) etc.) exhibiting antibacterial and antitumor activity [34]. In most cases, polyfunctional catechol thioethers were obtained by Michael reaction via the interaction of o-, p-benzoquinone and the

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

• in most cases. A triple Michael adduct, tetrahydrochromen-4-one, is also formed as a side product in a few cases with excellent diastereoselectivity. Keywords: arylidenemalonates; curcumins; cyclohexanones; diastereoselective synthesis; Michael reaction; tetrahydrochromenones; Introduction There is

• cascade triple-Michael (Michael/Michael/oxa-Michael) reaction between curcumins and isatylidene malononitriles, giving spiro-oxindoles in excellent yields and diastereoselectivities [36]. Sahu et al. introduced a one-pot multicomponent reaction of curcumin, arylaldehyde and 2-aminobenzothiazole to

• synthesize functionalized pyrimidobenzothiazoles [37]. An in situ generated conjugated α-cyanoester/malononitrile has been successfully employed as substrate in the double Michael reaction with curcumins by Lalitha et al. [38]. An organocatalytic cascade double Michael reaction between curcumins and 2

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

• , (2) a second intramolecular Michael reaction forming a head to tail formal [4 + 4] cycloadduct, and (3) sequential hemiketal formations to furnish the densely-functionalized and complicated pentacyclic scaffold of trichodimerol (2). Alternatively, the 2,4-cyclohexadienone moiety of 34 undergoes

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• come into play when synthesizing compounds. Last, we have an example of the Michael reaction in Scheme 1c. Here, both the experimental site of reaction and the ML-predicted site of reaction match. Our ML model predicts the lowest pKa value to be 12.5, whereas the second lowest ML-predicted pKa value is

• , Reaxys reaction ID: 9947221 [42]; (b) Claisen reaction, Reaxys reaction ID: 3402137 [43]; (c) Michael reaction, Reaxys reaction ID: 29819768 [44]. Arrow: experimental site; teal filled circle: ML-predicted lowest pKa. Comparing different ML models for predicting pKa values. Mean absolute error (MAE) and

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• ) [32]. The formation of the products can be explained by Michael reaction (1,4-addition) of 3 to the chromone and ring cleavage to give intermediate G. Subsequent Knoevenagel reaction by attack of the methylene carbon to the aldehyde resulted in the formation of the final products. The regioselective

• The reaction of dimethyl acetone-1,3-dicarboxylate (3) with 3-(methoxalyl)chromones 11a–g, a new type of chromone developed in our group, afforded benzophenones 21a–g in moderate to very good yields (Scheme 7) [38]. The formation of the products can be explained by Michael reaction (1,4-addition) of 3

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

• -carbonyl-based Michael acceptors. Results and Discussion Synthesis During our endeavors to identify potent Lewis-base catalysts for the oxa-Michael reaction [13][14], the triarylphosphine 1 was tested in a model reaction (2 equiv allyl alcohol, 1 equiv acrylonitrile, 0.05 equiv 1). However, no conversion

• 3.09 ppm, respectively, and two novel signals for tertiary butyl groups. Accordingly, we reasoned that the phosphine has reacted presumably with acrylonitrile forming a stable species not suited to catalyze the oxa-Michael reaction. In order to identify this compound, we reacted 1 with acrylonitrile or

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

• ) [34]. Encouraged by this, they have also attempted an intramolecular tandem conjugate addition/Michael reaction sequence, which has resulted in the expected cyclization product 30 in a diastereopure form (Scheme 7B). Zinc enolates readily react with allyl iodides 31 or the structurally similar Stork

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• steps from accessible methylcyclopentenone 16 (Scheme 2). The sequence included a Mukaiyama–Michael reaction with silyl enol 15 followed by a Tsuji alkylation. With diene 17 in hands, the RCM reaction was performed by addition of G-II catalyst and furnished the expected C5-C8 bicyclic framework 18 in 95

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• chemistry; levoglucosenone; oxa-Michael reaction; Introduction (−)-Levoglucosenone (1) is formed from the acid-catalyzed pyrolysis of cellulose along with minor amounts of furfural and 5-methylfurfural [1][2][3]. It has emerged as a promising starting material for enantioselective synthesis from materials

Sesquiterpenes from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346

• Wiriya Yaosanit,
• Vatcharin Rukachaisirikul,
• Souwalak Phongpaichit,
• Sita Preedanon and
• Jariya Sakayaroj

Beilstein J. Org. Chem. 2022, 18, 479–485, doi:10.3762/bjoc.18.50

• intensities of Hb-3, H-5, and Hab-15, indicating that the carboxyl moiety was α-orientated. Biosynthetically, compound 2 might be derived from compound 4 or compound 5 by oxa-Michael reaction of 7-OH to the α,β-unsaturated carboxylic acid moiety to form a tetrahydrofuran unit followed by ring opening of the

• lactone moiety and demethylation, respectively (Figure 4). Subsequent dehydration would afford compound 2 with an α,β-unsaturated carboxylic acid moiety. Alternatively, the ring opening of compound 4 and demethylation of compound 5 would occur prior to the oxa-Michael reaction. Accordingly, the absolute

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• Waser employed an isothiourea catalyst for esterification-mediated kinetic resolution of paracyclophane derivatives with planar chirality [19]. Parida and Pan showed that a Michael reaction coupled with an acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones can produce a

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

• Estelle Silm Ivar Jarving Tonis Kanger Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, 12618 Tallinn, Estonia 10.3762/bjoc.18.18 Abstract An asymmetric Michael reaction between cyclopentane-1,2-dione and alkylidene oxindole was studied in the

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• asymmetric aza-Michael reaction (aza-MR) alone or in tandem with other organic reaction(s) is an important synthetic tool to form new C–N bond(s) leading to developing new libraries of diverse types of bioactive nitrogen compounds. The synthesis and application of a variety of organocatalysts for

• organocatalysts in asymmetric aza-MR. Keywords: asymmetric aza-Michael reaction; covalent bonding catalysis; nitrogen heterocycles; non-covalent bonding catalysis; organocatalysis; Introduction The Michael reaction though discovered about 135 years ago [1][2] continues to attract attention of the chemists owing

• ][5][6][7]. The reaction involving a nitrogen-based nucleophile as the Michael donor is known as the aza-Michael reaction (aza-MR). In view of its ability to introduce a nitrogen-containing functionality at the β-position of an activated alkenyl- or alkynyl-substrate, over the years, it has developed

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• reactivity might be sufficient to overcome the reactivity limitations of pronucleophiles derived from other α-amino esters [42]. In this paper, we describe the use of cyclopropenimine catalysis for the enantioselective catalytic Michael reaction of α-substituted amino ester imines. Results and Discussion To

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• addition of cyclic 1,3‐dicarbonyl compounds, including 4-hydroxycoumarins 1, to α,β‐unsaturated enones 2 (Scheme 1). This versatile Michael reaction afforded (S)-warfarin (3a) and other Michael adducts 3 in high yields and good enantiomeric excess (ee), using (4S,5S)-4,5-diphenylimidazolidine-2-carboxylic

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

• triarylphosphines TPP, MMTPP and TMTPP as catalysts for the oxa-Michael reaction three varyingly strong Michael acceptors, namely acrylonitrile (1), acrylamide (2) and divinyl sulfone (3) were reacted with four different alcohols of similar molecular mass but different acidity (Figure 1). The stoichiometry of

• catalyst TPP is unable to promote the oxa-Michael reaction of the good Michael acceptor 1 (electrophilicity parameter E of −19.05 [19]) with the least acidic alcohol 2-propanol (a) as virtually no conversion was observed after 24 h. Using MMTPP leads to a minor improvement and a 3% conversion towards 1a

• poly4 exhibiting even lower Mn values (820 and 890 g/mol, Ð = 1.7 and 1.8) than those obtained in the room temperature reaction. Considering the distinctly higher double-bond conversions at 80 °C, these findings point to another double-bond consuming reaction beside the oxa-Michael reaction. The