Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• generating and activating Michael acceptors within a single catalytic manifold. Building upon the simple Lewis acid-catalyzed aza-Michael additions described in Scheme 8, copper-catalysis has been successfully extended to cascade processes, where the initial conjugate addition is followed by intramolecular

Chiral cyclopropenimine-catalyzed enantioselective Michael reactions of phenol and benzofuran-derived α,β-unsaturated pyrazolamides with benzophenone-imine of glycine esters

• Ya Bai,
• Xue-Ying Wang,
• Si-Kai Zhu,
• Yan-Ting Shen,
• Sheng-Yong Zhang and
• Ping-An Wang

Beilstein J. Org. Chem. 2026, 22, 888–896, doi:10.3762/bjoc.22.69

• series of 3-substitued glutamic acid esters in high yields and diastereoselectivities through DBU-catalyzed Michael additions of benzophenone-imine of glycine ester and α,β-unsaturated esters which derived from phenols and benzofurans under mild conditions [5][6]. The chiral 3-aryl-substituted glutamic

• and pyroglutamic acid esters were also produced by enantioselective Michael additions of β-aryl-substituted α,β-unsaturated pyrazolamides with benzophenone-imine of glycine ester in excellent ee and de values by using a chiral cyclopropenimine (Lambert catalyst, Figure 2b) as an organosuperbase

• base-catalyzed Michael reaction of 1a and 2a. The preparation of β-substituted α,β-unsaturated pyrazolamides 5. CSB-1-catalyzed Michael additions between compounds compounds 2 and 5. In situ acidic hydrolysis and lactamization of 6. The screening of reaction conditionsa. Supporting Information

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• , Michael additions, cycloadditions, domino reactions, cascade annulations, Diels–Alder reactions, and Michael–Stetter reactions, to name a few [31][32][33][34][35]. Notably, previous reports have demonstrated that the utility of chiral N-heterocyclic carbene (NHC) catalysts permits contracting asymmetric C

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• following subchapter) but also to other processes such as aza-Michael additions or processes catalyzed by species able to establish noncovalent interactions with the reactants [52][53][54][55][56][57]. Lewis acid-catalyzed carbonyl–ene reactions Similar to the Diels–Alder cycloaddition reaction, the Alder

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• include the products 137 through Strecker reactions, aldol-type condensations and phosphorus ylide-based olefinations (135) with subsequent Michael additions (138), or sulphinimine and ketone additions (140 and 141, respectively). These common functionalisations are also well documented in a recent

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• prominent Hayashi–Jørgensen catalyst. This prolinol silyl ether was independently discovered by the respective Hayashi and Jørgensen research teams in 2005 [13][14]. Interestingly, the use of prolinol alkyl ethers for asymmetric Michael additions, although at the time added in a stoichiometric manner, has

• ]. Kowalczyk and co-workers showed how asymmetric organocatalysis can benefit from mechanochemical activation. They established that Michael additions of thiomalonates to enones, catalyzed by cinchona-derived primary amines, is efficient and enantioselective under ball-milling conditions [24]. Kondratyev and

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• sulfhydryls can be conjugated by several means, including alkylation with α-halo carbonyls (in which case Lys may compete), and Michael additions (e.g., to maleimide, which is reversible and therefore may lead to incomplete conversion). The Michael adducts also present chemical instability in plasma and

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• ones with secondary amine side arm (48d, 48g, h) were catalytically active for Michael additions, providing 60–71% yields (Table 3), whereas tetraalkylated analogues (49a–g) and dialkylated OxPs without a secondary amine side arm (48a–c, 48e and 48i) were not. Based on these results, the authors have

• activation of both substrates via hydrogen-bonding interactions. Additionally, these macrocycles showed excellent activity for sulfa-Michael additions, as well as a moderate activity for Henry and aza-Henry reactions. These results are consistent with the observation reported by Senge and co-workers

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

• novel approach based on iminium catalysis employing chiral primary amines under ball milling conditions. Ball milling induces localized and transient temperature and pressure increases which could influence changes in the free activation volume [32][33][34], favoring Michael additions [35]. Furthermore

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

• 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

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

• organocatalysts is well-established in several organic reactions, including but not limited to aldol reactions [6], Michael additions [9], Mannich reactions [10], aza-Henry reactions [11], and Diels–Alder cycloadditions [12][13]. Although the benefits of organocatalysts are undoubted, their synthesis is often a

• (Figure 1). Results and Discussion Synthesis of the lipophilic cinchona squaramide organocatalyst Previously, we successfully applied quinine-derived squaramide (SQ) organocatalyst 1 in stereoselective Michael and aza-Michael additions with excellent enantiomeric excess values [26]. Our aim was to recycle

New advances in asymmetric organocatalysis

• Radovan Šebesta

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

• variety of enantioenriched 1,5-dihydro-2H-pyrrol-2-ones [20]. The development of any area is critically dependent on the understanding of underlying features and relationships. Slugovc and co-workers provide such mechanistic investigation of phosphine-catalyzed Michael additions [21]. Chiral

• possibilities in combination of covalent and noncovalent activation, our group designed and synthesized N-sulfinylpyrrolidine-containing ureas and thioureas and applied them in Michael additions of aldehydes to heterocycle containing nitroalkenes [25]. Dubey and Chowdhury showed that 1,4-conjugate additions of

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

• malonates [25]. Herein, we report the results of an asymmetric organocatalytic Michael addition of CPD to alkylidene oxindoles. Results and Discussion Chiral multifunctional thioureas [26][27] and squaramides [28] are extensively used as catalysts in asymmetric Michael additions. We believed that a

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• Michael additions of aldehydes to nitroalkenes both under solvent-free conditions and in solution. The N-sulfinylurea catalyst was more efficient than the corresponding thiourea. For some substrates, enantioselectivities reached 98% ee. The stereogenic center on the sulfur did not have a considerable

• organocatalytic transformations were successfully performed under solvent-free ball-milling conditions [30][31]. In this context, we describe the synthesis of new pyrrolidine appended sulfinylurea and thiourea organocatalysts and their assessment in Michael additions of aldehydes to nitroalkenes. Furthermore, we

• ). Michael additions under solvent-free reaction conditions To evaluate the applicability of the new catalysts C1 and C2, we decided to test them in the Michael addition under solvent-free conditions. Ball-milling experiments were conducted in a mixer mill, in which the milling vessels perform radial

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

• -1,2,3-triazoles 35 in good yields (up to ≈72%) and excellent enantioselectivity (up to 99% ee) (Table 7) [41]. In an interesting study, Wu et al. screened a number of cinchona derivatives and squaramides for their relative catalytic efficacies for the enantioselective aza-Michael additions between

• -quinolones 92 in very good yields (67–95%) with high ee (82–97%) (Table 20) [59]. Following a similar approach, Yang et al. reported asymmetric aza-Michael additions of anilines 94 to β-nitrostyrenes 93 using a chiral binol-derived phosphoric acid diester catalyst (cat. 95). They succeeded in preparing β

• chiral N-triflylphosphoramide. Aza-Michael addition of primary amines to β-trifluromethyl-β-phenylnitroolefin catalyzed nitrogen heterocyclic carbene. Asymmetric aza-Michael additions of pyrroles to protected (E)-4-hydroxybut-2-enals. Asymmetric aza-Michael addition of purine bases to aliphatic α,β

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

• triphenylphosphine (TPP) in catalyzing oxa-Michael additions. A matrix consisting of three differently strong Michael acceptors and four alcohols of varying acidity was used to assess the activity of the three catalysts. All test reactions were performed with 1 mol % catalyst loading, under solvent-free conditions

• TPP (618.7 kJ/mol) [37]. However, for PMe3, discussed as a model for aliphatic phosphines, a distinctly lower MCA of 604.2 kJ/mol was calculated. This is in contrast to experimental data as PMe3 is known as a more active catalyst for oxa-Michael additions than arylphosphines [8][14]. Apparently, the

• resulted in using B3LYP-D3 /TZVPPD + Δsolv (B3LYP-D3) + ZPE,temp (PBE-D3/def2-SVPD). General procedure for oxa-Michael additions The alcohol (2.0 equiv for mono-functionalized Michael acceptors, 3.0 equiv for 3) and the catalyst (0.01 equiv) were added to a 4 mL-sealed tube. Then, the Michael acceptor was

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

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

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• sulfa-Michael additions of thiols to chalcones with sulfonamide-type organocatalysts in the literature [30][31], in this study, a new quinine sulfonamide organocatalyst derivative was developed to catalyze the enantioselective SMA of naphthalene-1-thiol to trans-chalcones under mild conditions and with

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

• notable features of this method, which is worthy of attention. Furthermore, the high electrophilicity of ynones 2 obtained was nicely demonstrated through two representative reactions, namely 1) Michael additions of β-keto carbonyl compounds and 2) amidines and guanidine for the construction of aromatic

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• oxa-Michael additions of 2’-hydroxychalcones [9][10], or through condensation cyclization reactions of o-hydroxyacetophenones with ketones/aldehydes [11][12], in addition to other alternative transformations [13][14]. Moreover, radical cascade cyclizations of o-allyloxybenzaldehydes by employing

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• -containing enoate derivatives 1i and 1j were easily transferred to the corresponding ring-opened N-alkylated triesters 3i and 3j containing two C=C bonds which could be important as precursors for double Michael additions, and were isolated in 71% and 58% yields. The above described synthetic system has been

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• diastereoselectivity remains constantly high in all solvents [19]. Unfortunately, the enantioselectivity of the Michael additions remained moderate with both catalysts in all tested solvents and conditions, only rising to 84% ee when using catalyst 3 in toluene. The reason of the better catalytic performance of PFA

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• (−)-Isoguaiene was prepared from (S)-citronellal in only 9–10 steps with good overall yields. Either a trienyne or a dienediyne metathesis and highly diastereoselective organocatalytic Michael additions of aldehydes derived from (S)-citronellal served as the key transformations. Keywords: domino reactions

• sesquiterpene (−)-isoguaiene (1) using either a trienyne or a dienediyne metathesis and highly diastereoselective organocatalytic Michael additions of aldehydes derived from 5 as the key steps. Structures of the sesquiterpene (−)-isoguaiene (1) and the trisnorsesquiterpene clavukerin A (2). Retrosynthetic

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• enantioselective reactions (mainly because of the nucleophilic center on the chiral quinuclidine skeleton) [20]. More importantly, they are a privileged class of chiral catalysts, which are well known for their use in Michael additions [21], Morita–Baylis–Hillman reactions [22], and aldol reactions [23], among