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

• functional groups are found in various drugs, natural products, and optoelectronic materials. In the last three decades, N-heterocyclic carbenes (NHCs) have been renowned as versatile organocatalysts, including thiazolium, imidazolium, and triazolium moieties. NHCs are extensively used in many catalytic

• ][47][48][49][50]. This review focuses on recent synthetic developments of NHC-catalyzed, visible-light-promoted dual organophotocatalysis for preparing carbonyl compounds and related organic intermediates by combining NHC and organic photocatalysts. Organocatalysts have a significant impact on the

• presence of NHC (10 mol %) and 4CzIPN (2 mol %) and Na2HPO4 in DMSO at rt for 10–24 h. The key to success lies in the photocatalytic dual system, which combines two organocatalysts (NHC/4CzIPN) and visible light irradiation to permit a novel umpolung single-electron reduction of respective imino ester 2

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

• enantioenriched catalysts ranging from chiral organometallic complexes to organocatalysts (small organic molecules) have been designed, synthesized, and successfully used in several organic transformations [1][2][3]. Despite these advances, catalytic methods involving radical intermediates were very rare until

• . The past three decades have seen enormous advances in the development of enantioselective radical reactions, particularly using organocatalysts. Some of the notable chiral organocatalysts imparting enantioselectivity include chiral secondary amines, chiral Brønsted acids, and chiral H-bonding

• . Melchiorre and co-workers reported a dual catalytic system that involves photoredox and chiral organocatalysts for the construction of all-carbon quaternary centers. The authors studied radical additions to β,β-disubstituted cyclic enones (Scheme 7) [29]. The dual catalytic system of tetrabutylammonium

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• transition-metal complexes such as the Grubbs’ second-generation metathesis catalyst, NHCs are now also well-established as organocatalysts. With the first application pre-dating the unambiguous characterization of a free NHC by nearly 50 years, NHCs can facilitate numerous synthetically attractive

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

• been developed, employing enzymes, metal complexes, or organocatalysts to convert prochiral or meso precursors into chiral motifs. Different from other strategies constructing chiral centers by formation of a new chemical bond at the central carbon, enantioselective desymmetrization is achieved through

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• with the more recently introduced inherent chirality. As one of the most prominent chiral organocatalysts, chiral phosphoric acid (CPA) catalysis has proven highly effective in synthesizing centrally and axially chiral molecules. However, its potential in the asymmetric construction of other types of

• leveraging the synthesized enantioenriched aza[6]helicene 29a and tetrahydro[6]helicene 30a as chiral building blocks, a series of helically chiral organocatalysts and ligands could be easily prepared, such as the helically chiral pyridine N-oxide 31a and helically chiral monophosphine ligands 31b,c, whose

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• highly efficient catalysts, chemosensors, and functional materials. We have recently made strides in developing macrocyclic organocatalysts; however, their synthesis remains challenging. In this work, we aimed to discover a straightforward method for producing a diverse range of chiral macrocycles

• , thereby enabling further exploration in the field of interlocked and macrocyclic organocatalysts. We successfully established optimized synthetic routes for the synthesis of chiral macrocycles containing one or two stereogenic units, featuring varying ring sizes and substituents (21 examples in total

• [56]. Synthesis of macrocycles featuring two BINOL units For the synthesis of macrocycles featuring two BINOL units, our first goal was the introduction of two hexaethylene glycol chains between the two BINOL units. These derivatives had proven to be highly efficient organocatalysts in our earlier

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

• of the resulting products in developing chiral organocatalysts was investigated as well. For instance, 28a was converted to a thiourea-tertiary amine 29 through a four-step procedure in an overall 36% yield. This compound was then utilized as the catalyst in the electrophilic amination reaction

• chiral products, e.g., biological activities and utility as chiral organocatalysts or ligands, warrants greater attention. We anticipate that considerable efforts in these directions would be crucial for advancing this field and fully unlocking the synthetic potential of isocyanides in the preparation of

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• important role as building blocks for peptide synthesis [1][2][3][4][5], as organocatalysts [6][7][8][9][10] and as enzyme inhibitors [4][11][12][13]. The incorporation of such amino acids into peptides can, for example, influence peptide conformation, the binding affinity to receptors [14], as well as

New advances in asymmetric organocatalysis II

• Radovan Šebesta

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

• commonly defined as a form of catalysis where a small organic molecule, an organocatalyst, accelerates a chemical reaction. Unlike previously regarded traditional catalysts involving metals or enzymes, organocatalysts are composed of nonmetal elements, such as carbon, hydrogen, nitrogen, oxygen, phosphorus

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

• , fragrance chemicals, organocatalysts, and peptides. This comprehensive review summarises developments in this field during the period 2010–2024. Keywords: conformational analysis; medicinal chemistry; organofluorine chemistry; stereoselective fluorination; Introduction In the art of origami, a

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• diastereoselectivity at 50 °C (Table 1, entry 16). Finally, the addition of molecular sieves was evaluated (Table 1, entries 17 and 18) affording in both cases lower yields for the reaction product. We also attempted asymmetric reactions using chiral organocatalysts to achieve an enantioselective outcome; however, we

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• ]. In addition, cyclic diaryl λ3-bromanes have been successfully employed as halogen-bonding organocatalysts in Michael addition [8] and their chiral variants were efficient in catalyzing enantioselective Mannich reactions of ketimines with cyanomethyl coumarins [9] and malonic esters [10]. These

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• , although the synthesis and characterization (particularly crystallization) of low-symmetry structures remains challenging [227][231][232]. Likewise, COFs hosting chiral organocatalysts are known (Figure 6B) [226][233]. Frameworks are well-suited to hosting opposing reactive functionalities (e.g., acids and

• organocatalysts [222][234] all suffer from the same limitation: they all fail to rigidly organize sufficient bifunctional groups to obtain clear transition-state binding – a hallmark of enzymes and organocatalysts [107][180]. Strategy towards organocatalytic organic cages: My laboratory has levied the following

• synthesis of self-assembled, robust organic cages with internal functionality [38][39][40][41][42][43][44]. Robust organic cages are under-represented in the supramolecular catalysis and enzyme-mimicry literature, an observation which correlates strongly with the lack of cavity-based organocatalysts. The

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• -d]pyrano[4,3-b]pyran-, furo[2',3':4,5]pyrano[3,2-c]chromene-, and furo[2,3-d]pyrimidine carboxylates were obtained from the reactions of alkyl 3-bromo-3-nitroacrylates with representatives of carbo- and heterocyclic CH-acids under simple conditions, without the use of organocatalysts. The structures

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

• purities in this process (Scheme 20). Chiral Brønsted acid-catalyzed atroposelective reactions Chiral Brønsted acids became prominent organocatalysts that also promote the syntheses of axially chiral compounds. The amination of aromatic biaryls 65a–g with dibenzylazodicarboxylate catalyzed by

• %. An extensive study on the reactivity of o-naphthoquinones 117 and 122 with 2-naphthylamines, 2-naphthols (118, 120), and indoles 123 was done in 2019 (Scheme 37) [65]. Four organocatalysts ((S)-C23, C31, C32, (R)-C23) proved the most efficient, and stereoinformation was effectively transferred in all

• of the naphthol's OH group and indole's NH group, presumably through hydrogen bonding with organocatalyst C27. The organocatalytic atroposelective preparation of promising EBINOL scaffolds 167 and 169 was done by Wang et al. with the help of the SPINOL-derived organocatalysts C40, C41, and C42

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

• -heterocycles using various catalytic systems such as chiral metal catalysts, chiral Lewis acids or chiral organocatalysts. This review presents an overview of the recent advances in enantioselective cyclization reactions of 1-azadienes catalyzed by non-covalent organocatalysts. Keywords: α,β-unsaturated

• ]. Although quite important in all organocatalytic processes, there are specific organocatalysts which activate reactants through non-covalent interactions such as hydrogen bonding. These interactions are crucial to obtain high enantioselectivity in the reaction. The 1-azadienes possess an electronegative

• example. This review discusses different examples involving IEDADA reactions and other cyclizations, with a special focus on the mode of action of the organocatalysts, and aims to show the synthetic applicability of the formed cyclic derivatives. The three non-covalent organocatalysts which will be

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

• applied in various fields, including organometallic catalysis, dye-sensitized solar cells, sensing, artificial olfactory systems, photodynamic therapy (PDT), anticancer drugs, biochemical probes, and electrochemical devices. Relevant examples of these two pyrrolic macrocycles as metal-free organocatalysts

• Metal-free tetrapyrrolic macrocycles as supramolecular organocatalysts Supramolecular organocatalysis has recently attracted emerging attention as a green alternative to metal-based catalysis [24][25][26]. Organocatalysis using macrocyclic scaffolds such as crown ethers, cyclodextrins, cucurbiturils

• active groups for a variety of substrates, making their use as supramolecular organocatalysts based on bifunctional activation mechanism (hydrogen-bonding/Lewis basicity) highly promising. At the same time, additional functional groups that are required for the catalysis can be easily installed on the

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

• organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen”, an interesting approach to recycling the very useful cinchona squaramide organocatalysts was described. This approach involved functionalization of the organocatalyst with a lipophilic linker (octadecyl side chains), resulting in a

• contributed to this thematic issue, Fehér et al. [22] carried out a critical assessment of the factors that affect the activity of immobilized organocatalysts. As mentioned earlier, organocatalysis has proven to be a powerful tool in the preparation of enantiopure compounds. However, their preparation can be

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• (Figure S6, Supporting Information File 1). Therefore, in order to observe the coupling between these two moieties under standard conditions, the presence of a catalyst is necessary. In the literature, metal-based and organocatalysts have been reported as efficient catalysts for this reaction [24][25]. As

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• many organocatalysts [3][4][5], natural products (e.g., the potent α-glucosidase inhibitor (−)-codonopsinol B) [6][7], and pharmaceutical drug molecules such as saxagliptin and ramipril (Figure 1) [8]. Accordingly, the development of methods to access substituted prolines and pyrrolidines is an

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• for the resolution of chiral amines [28]. However, it was not until 2004 that they were recognised as efficient chiral Brønsted acid organocatalysts for asymmetric Mannich reactions [29]. Malkov and co-workers revealed [30] that (R)-TRIP can act as a very efficient catalyst for the kinetic resolution

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• . Keywords: catalyst design; machine learning; modelling; organocatalysis; selectivity prediction; Introduction Since the beginning of the 21st century, organocatalysts [1] have established themselves as a third group of homogeneous catalysts, next to biocatalysts [2] (enzymes) and transition metal-based

• -trivial, even for highly experienced experts. Thus, intuition-guided catalyst development is regarded as suboptimally efficient and furthermore highly subjective to the experience of the chemists carrying out the study [10][11][12][13][14][15]. Considering the demand of organocatalysts, their accelerated

• and reliable development is highly desirable [16]. In the spirit of accelerated discovery, the development of organocatalysts has been augmented with computational catalyst design [17][18]. Multiple programs for automated catalyst simulation have been developed in the last decade. Notable examples

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• ). Results and Discussion Reaction optimization Over the past two decades more than 300 various catalytic systems have been proposed for Biginelli chemistry, e.g., simple inorganic and organic acids, metal salts, metal oxides, ionic liquids, phosphines, nanocatalysts, organocatalysts, ion exchange resins [1

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

• , providing a cost-effective alternative to traditional catalytic methods. The immobilisation of organocatalysts offers the potential to increase catalyst reusability and efficiency in organic reactions. This article reviews the key parameters that influence the effectiveness of immobilised organocatalysts

• , including the type of support, immobilisation techniques and the resulting interactions. In addition, the influence of these factors on catalytic activity, selectivity and recyclability is discussed, providing an insight into optimising the performance of immobilised organocatalysts for practical

• applications in organic chemistry. Keywords: asymmetric synthesis; catalyst recycling; heterogenisation; organocatalysis; solid support; Introduction Organocatalysts are small molecules that do not contain a metal atom in the reaction centre and are able to increase the speed of reactions. They have proven

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

• catalysts Noncovalent organocatalysts display a few advantages compared to the traditional metal Lewis acids, such as lower environmental impact, higher stability to air and moisture, easier removal from the GBB products. In this regard, Bolotin et al. in 2022 have reported the high catalytic activity of

• of chalcogen-based noncovalent organocatalysts. In 2023, Bolotin et al. published another article on the same subject [15], reporting a general improvement of electrophilic activation of carbonyl and imino groups by synergetic effect of aryl iodonium salts and silver cations. However, when similar