Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• -hydroxy-β-lactams or 2-hydroxycyclobutanones can function either as inherent structural motifs in target natural products or as strained reactive intermediates, facilitating C–H functionalization via four-membered ring opening [6][7][8][9][10][11]. Quinones display distinct photochemical reactivities

• ring, constructing 86 – setting the stage for the group’s key reaction, in which α-hydroxy-β-lactams (e.g., 87) serve as surrogates for α-metalated N-heterocycles in Pd-catalyzed coupling with aryl halides. Both enantiomers of 87 (only one shown in Scheme 10) participated in a Pd-catalyzed

• stereoretentive coupling at C2 with aryl bromide 86, yielding 88 as a single diastereomer. Manipulation of the protecting group of 88 arrived at lycoplatyrine A (89). Notably, 87 and related α-hydroxy-β-lactams were obtained via Norrish–Yang cyclization of the corresponding neat α-keto amides in the solid state

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• photoenzymatic transformation developed by the Hyster group, α-chloroamides were converted to enantioenriched 5-, 6-, 7-, and 8-membered lactams through an enantioselective radical cyclization followed by a diastereoselective HAT, producing contiguous stereocenters [75]. In the subsequent year, the same group

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• oxygen in alcoholic medium has also been reported (Scheme 37) [121][122]. Riguet synthesized γ-lactams through a Ugi 4-center 3-component reaction (U-4C-3CR) protocol. HFO was used as the electrophile in the Friedel–Crafts (FC) alkylation reactions of indole catalyzed by diphenylprolinol silyl ether. The

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• ]. Encouraged by the above results, we turned our attention to biaryl lactams [49]. However, in this case, the inherent resonance stability of the amide bond makes the ring-opening process rather challenging. To solve this problem, we envisioned that a cooperative catalytic system merging silver catalysis and

• organocatalysis could be employed to activate both reactants simultaneously. After extensive screening, the combination of Ag2CO3 and quinidine-derived squaramide C2 was identified to be the optimal choice of catalyst. A variety of ortho,ortho-disubstituted biaryl lactams 48 were facilely transformed into the

• corresponding tetra-ortho-substituted atropisomeric anilines 49 in high yields with excellent enantioselectivities (Scheme 8b). In contrast, lactams possessing only one ortho substituent suffered from much lower reactivity (e.g., 49c), presumably due to the lack of sufficient torsional strain [50], whereas

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• of alkenylboronic esters using energy transfer catalysis [26]. Gualandi and co-workers leveraged a combination of photoredox and HAT catalysis to realize the intramolecular nucleophilic amidation of alkenes with β-lactams [27]. Further, Luridiana and colleagues developed a method for the alkylation

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• yield of up to 99%, with excellent regio- and E-selectivities. The method could be used for functional-group transformations of amines, amides, and lactams, as well as for gram-scale syntheses, demonstrating synthetic usefulness and versatility. A complementary Full Research Paper by Martina and co

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• corresponding lactams 29d and 29e and amines 29f and 29g were also obtained. Compounds 29a and 29b exhibit λabs centered at 513 nm, while the amines 29f and 29g display high ФF values of 0.48 and 0.56, respectively. Notably, azocine derivative 29b exhibits the highest CPL activity among the series, with a |glum

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• compatibility with primary, secondary, and tertiary bromides, yielding benzo-fused lactams with good functional group tolerance, thereby highlighting the method’s versatility for the synthesis of diverse bioactive molecules. The proposed mechanism involves the initial generation of alkyl radical 69 from α

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• to 429 (Scheme 88A) [149]. On the other hand, Novikov and co-workers (2019) utilized Rh(II) to catalyze the [2 + 1 + 1] assembly of spiro β-lactams 431–434 from diazocarbonyl compound 430 and azirines via Rh carbenoid 435 followed by aziridine ring-opening (436 and 437) (Scheme 88B) [150]. Lv and co

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• conditions and shows broad applicability to di- and trisubstituted allenes. Its practicality is demonstrated through the gram-scale synthesis and functional group transformations of amines, amides, and lactams, emphasizing its versatility and synthetic significance. Keywords: α-quaternary nitrile; Cu

• synthesis and the successful transformation of nitrile products into amines, amides, and lactams. Further studies are underway to broaden the scope and application of the proposed method. Synthesis of acyclic nitrile-substituted quaternary carbon centers from allenes. Hydrocyanation of allene 1a with tosyl

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

• final products, however, it can be released after a decarboxylative or reductive reaction (β-position), allowing the use of ethyl glyoxylate as a C1 building block. This strategy was explored by Miranda et al., who first obtained a series of γ-lactams 56 and isoindolinones 57 using ammonium persulfate

• radical species of the ammonium persulfate salt. Subsequently, the radical delocalization process gives rise to the carbon-centered radical, which follows the intramolecular cyclization onto the double bond or onto the aromatic ring depending on the case. The γ-lactams 56 and isoindolinones 57 can

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• . Review 1 Transformations via the formation of copper nitrenoids 1.1 C(sp3)–H amidation Lactams are recognized as one of the most significant nitrogen-containing heterocycles in drug discovery [69][70]. Among these, six-membered lactams, known as 2-piperidinones, have been extensively studied due to their

• potential bioactivity [70][71][72][73]. Despite the development of synthetic approaches for six-membered lactams, including transition-metal-catalyzed transformations, several limitations remain, particularly with regard to regioselectivity and asymmetric C–N bond formation, which are still limited. In 2023

• , the Chang group elegantly unveiled a protocol for an enantioselective C–N bond formation, introducing δ-lactams from dioxazolones using a copper(I) catalyst and a chiral BOX ligand [74]. As shown in Scheme 2, dioxazolones containing aryl and heteroaryl groups were converted into the corresponding

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

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

• enantiomeric ratio retained. In September 2023, Lan, Huang, Yan and co-workers reported a phosphoric acid-catalyzed enantioselective reaction of acyclic α,β-unsaturated imines and azlactones enabling through an aza-inverse electron demand Diels–Alder reaction, the synthesis of chiral 3‑amino-δ-lactams (Scheme

• (56–90% ee). Furthermore, under the optimized conditions, the reaction between chalcone-derived azadienes 84 and azlactones 15 was carried out obtaining the chiral 3‑amino-δ-lactams 85 in moderate yields (27–57%), good to excellent diastereoselectivities (5:1 to >20:1 dr) and excellent

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• obtained intermediates with the appropriate commercial lactams, under microwave irradiation (Scheme 8). As a result, compound 8a has been identified as a promising derivative potentially useful in further AD drug discovery for its antioxidant activity (4.7 TE in ORAC-FL assay), moderate hAChE inhibition

• of the nitrogen in lactams 11 with an oxygen in 12 to influence hydrogen-bond donating properties and synthesis of the benzodioxepinone derivatives via Passerini reaction. MCR 3 + 2 reaction to develop spirooxindole, spiroacenaphthylene, and bisbenzo[b]pyran compounds. Synthesis of ML192 analogs

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• reactions limit the utility of this approach. Herein, we report an intramolecular photoredox cyclization of alkenes with β-lactams in the presence of an acridinium photocatalyst. The approach uses an intramolecular nucleophilic addition of the β-lactam nitrogen atom to the radical cation photogenerated in

• lactams. Notably, all reported structures have alkyl or aryl substituents in position 3 of the clavam ring. Conversely, clavams substituted with alkyl chains at the 2-position, to the best of our knowledge, have not been previously reported and are absent from common organic compound databases. To explore

• -lactams to photooxidized alkenes (Figure 2A), and our findings are presented in this study. Results and Discussion The initial phase of our investigation involved the synthesis of suitable starting compounds for the following oxidative cyclization. For this purpose, a series of 4-alkoxy-β-lactams

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• substituent in the exocyclic acyl group by introducing different N-, O-, and S-nucleophilic reagents into the reaction. The reaction of chiral diazotetramic acids leads exclusively to trans-diastereomeric β-lactams. The use of variously substituted diazotetramic acids, including spirocyclic derivatives, as

• well as a wide range of nucleophiles provides access to a structural diversity of medically relevant 2-oxoazetidine-3-carboxylic acid amides and esters. Keywords: β-lactams; diazotetramic acids; nucleophiles; spirocycles; thermolysis; Wolff rearrangement; Introduction The importance of the β-lactam

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• as a 1:1 mixture of diastereomers (Scheme 4). The same procedure was also applied to estrone to insert the spiro moiety at C-17 in 70% yield [14]. Spiro-β-lactam steroids A novel one-pot procedure to build spiro-β-lactams from enamides was described by Liu et al. The research group had previously

• reaction times. Notably, 6-endo N-cyclization to form 2-piperidinones was not observed (Scheme 5). Using this protocol, a series of spiro-β-lactams were synthesized, with only the structure of the aryl moiety being varied. It is noteworthy to consider that the formation of two vicinal quaternary chiral

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• biologically relevant compounds, which include prostaglandins [65], β-lactams [66][67], homatropine [68][69] among many more [70] (Figure 3), reinforce the importance of the Cannizzaro reaction. Modifications of both intermolecular and intramolecular Cannizzaro reactions have been observed in numerous

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• herein an enantioselective palladium-catalyzed Heck–Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-1H-pyrroles with aryldiazonium salts, using the chiral N,N-ligand (S)-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation

• -pyrroles posed some challenges due to substrate instability and undesirable side reactions. In 2003, we reported the Heck–Matsuda arylation of N-protected 2,5-dihydro-1H-pyrroles [10] to obtain 4-aryl-γ-lactams in a racemic manner [11], thus demonstrating the feasibility of this transformation. The γ

• Heck adducts (methyl N,O-acetals) were efficiently converted into several arylated γ-lactams by a simple oxidation procedure (Jones oxidation). To demonstrate the applicability of the strategy, two of the chiral aryl-lactams were further derivatized to provide the selective phosphodiesterase-4

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• lactams). The second approach, which asserts its universality, frequently displays inadequate yield of target compounds. As such, the endeavour to discover novel approaches for synthesizing N-heterocycle-glutarimide ensembles of type 1 persists as imperative. Aliphatic diazocarbonyl reagents are widely

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• ], trifluorinated α-methylene-γ-lactams [99][100], and β-trifluoromethyl-β-acylhydrazonyl carbonyl compounds [101] (Scheme 15). Among these fluorinated products, the trifluoromethylated homoallylic acylhydrazines were easily transformed to CF3-substituted pyrazolines and 1,6-dihydropyridazines via a cascade

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

• ) [82]. In the method, functionalized γ-lactams 102 were produced in aqueous media with high enantioselectivities. However, N-(alkylsulfanyl)succinimides and α-isobutyl containing butyrolactam did not work in this reaction. Another work by Denmark on intramolecular sulfenylation of alkenes 119 with

• basic nature. However, the electron-poor ones exhibited less autocatalysis effect requiring the use of the Lewis base catalyst P. In 2019, Denmark and Panger disclosed a novel method for the preparation of γ‑lactams 133 through the reaction of alkenes 132 with N-thiophthalimides 14 in the presence of

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• lactams 1, 2b, and 3 (i.e., cleavage of Ar–N bond or removal of >C(CH3)2 or >C=O bridge) leads to secondary α-bromo(phenyl)acetamides 4a and 4b. When α-bromoamide 4a was treated with thiobenzamide without any base (entries 1 and 7 in Table 3), 2,5-diphenyl-1,3-thiazol-4-ol (13) was the only product