Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• quantitative yield and with a great enantiomeric excess of >99% ee (Scheme 2). Trifluorinated derivatives of leucine The fluorinated alkyl iodide is commercially available but costly. Thus, we aimed at establishing an appropriate synthesis for this iodide. Our previous work showed that fluorinated alkyl

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• bearing various functionalities. Notably, no erosion of enantiomeric excess was observed during any of the transformations. Double CuH insertion into alkynes for regiodivergent allylic substitution Generating chiral secondary alkylcopper species in situ through sequential hydrocupration of terminal

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

• additive (entries 10–13, Table 2), but none of the tests performed led to an improvement in enantioselectivity. We also studied the influence of the reaction temperature by performing two tests at 0 °C (entries 15 and 16, Table 2). We observed that the reaction occurs more slowly, and the enantiomeric

• excess reached is lower than at room temperature. Additionally, when the reaction mixture was stirred at −18 °C, no change was observed after 100 hours (entry 14, Table 2). These results led us to raise the reaction temperature to 31 °C (entries 17–20, Table 2). We observed that the retro-Michael

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• formed. The use of a chiral aryl iodide was tested, which gave products with low enantiomeric excess. However, these preliminary trials represent the first example of a catalytic, enantioselective HVI-mediated fluorocyclisation. The authors proposed a mechanism (Scheme 4) for this reaction that involved

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

• enantiomeric excess (ee) up to 5.5% [70]. Related catalytic systems based on amphiphilic 5-(cyclic-secondary-amine)-10,15,20-tris(4-sulfonatophenyl)porphyrin macrocycles 58–61 act as switchable organocatalysts for Michael and aldol reactions in water [68][69]. The macrocycles 58–61 containing different chiral

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• by Linclau et al. They have reported that the asymmetric Sharpless dihydroxylation of readily available (E)-5-bromo-4,4,5,5-tetrafluoro-2-penten-1-ol derivative 6 led to the corresponding chiral diols 7 with an excellent enantiomeric excess, 96% ee (reaction 1 in Scheme 1) [20][21]. It has also been

• published that the asymmetric conjugate addition of 4-methylphenylboronic acid towards (E)-5-bromo-4,4,5,5-tetrafluoro-1-phenyl-2-penten-1-one (8) in the presence of a rhodium catalyst coordinated with (S)-BINAP gave the corresponding Michael adduct 9 in 94% enantiomeric excess (reaction 2, Scheme 1) [22

• high enantiomeric excess (90% ee for (S)-23d and (S)-23e). Furthermore, it was found that the substituent position on the aromatic ring did not significantly influence the reaction efficiency as well as optical purity and the reaction proceeded in a highly enantioselective manner (91% ee for (S)-23f

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• a moderate 40% yield, but impressively high enantiomeric excess of 83%. To further validate the mechanistic pathway of the reaction, the authors conducted both radical trapping experiments and controlled experiments. These investigations conclusively demonstrated that the reaction did not proceed

• catalytic strategy provided direct access to a range of chiral spiropyrazolones in good to high yields, displaying moderate to excellent enantiomeric excess (Scheme 47, 47a–l). The method represents a novel approach for the synthesis of enantioenriched spirocyclic compounds with structural complexity

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

• Boltzmann constant, T is the temperature in Kelvin, h is the Planck constant, and R is the gas constant. The enantiomeric excess (%ee) was calculated using Equation 2 [41]. kfav stands for the kinetic rate constant of the most favourable process, and kdefav stands for the rate constant of the less

• mechanism leading to the (S) product presents an asymmetric TS, 1.2 kcal·mol−1 higher in energy than that of the (R) mechanism. Thus, the asymmetric catalyst enables to generate an enantiomeric excess of 95% with the (R) product being the most abundant product. Surprisingly, a transition state connecting

• now yield the same product, it is necessary to recalculate the %ee, but this time using an effective rate constant keff (Equation 3). In doing so, a small increase in enantioselectivity is observed, with now a (R) enantiomeric excess of 96%ee. The designed catalyst enables the generation of an almost

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

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

• structural overlap is present [121]. For every reaction, the imine is categorised as either an E- or Z-imine, based on the sign of the recorded enantiomeric excess. Further, molecular descriptors, either physicochemical properties or topological, are calculated for all reaction partners. This data is used to

• important to consider catalysts achieving high enantiomeric excess (ee) on relevant reactions, the deployment of general catalysts that provide a reasonable ee for a variety of reactions has gained more attention over the last years [128][129][130]. Catalysts that fulfil such demands are coined ‘general

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

• prolinamide-thiourea organocatalyst onto commercially available resins (JandaJel, polystyrene-divinylbenzene, and ChemMatrix) results in diminished catalytic activity, both in terms of yield and enantiomeric excess values, compared to the homogeneous analogue [117]. On the contrary, Dumesic and co-workers

• washing the resin with triethylamine between reaction cycles was sufficient to regenerate the catalyst. Consequently, high yields (85–94%) and enantiomeric excess values (90–92%) were consistently achieved over 9 reaction cycles. In a previous work conducted in our research group, we investigated the

• no significant differences in terms of yields. However, catalysts C30 and C31 achieved higher enantiomeric excess values (up to 79% ee and 59% ee, respectively) compared to catalyst C29 (up to 31% ee). Among the immobilised catalysts, C30 produced the best results. Catalyst C29, which showed lower

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• compounds 4a–j were also obtained in very good yields (60–98%, Scheme 2). Since the reaction mechanism proceeding with a Wagner–Meerwein rearrangement does not cause racemization or a diastereomeric mixture and preserves the initial enantiomeric excess in the camphene's fluoroalkoxy derivatives (Scheme 4

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• (imidazolidin-4-one) derivatives, Ia–c and IIa–c, analogous to well-known tridentate chiral ligands such as PyBOX [15] and PyBidine [16]. The copper(II) complexes of these ligands demonstrated remarkable enantioselectivity in asymmetric Henry reactions, achieving enantiomeric excess values exceeding 90% in

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

• (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

• reaction in which acetylacetone (13) did not only act as a reactant but also as a solvent was examined (Table 2). The highest yields and enantiomeric excess values were reached in CPME, toluene, and dichloromethane (Table 2, entries 1–3). When acetylacetone was used as solvent, the enantiomeric excess was

• (Figure 2). Considering the three factors mentioned above (yield, enantiomeric excess, and green chemistry), toluene was chosen as a solvent for the recycling reactions. The schematic for the recycling by solvent replacement is shown in Figure 3. After the stereoselective Michael addition was completed in

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• reaction between α-naphthol (17) and methyl 2-acetamidoacrylate (18) but promising selectivity was not achieved. The highest enantiomeric excess of 64% was obtained in the presence of P7 as the catalyst (Scheme 6) [30]. In 2018, Reddy and co-workers developed a one pot protocol comprising oxidation and an

• enantiomeric excesses. However, N-unsubstituted 49 (R1 = H) resulted in a much diminished stereoselectivity. As the electrophilic partner, isatin-derived ketimine was also utilized which furnished the product with 68% enantiomeric excess. Replacement of the nucleophile in this methodology for substrate scope

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• imines 25 (Scheme 6). The authors also demonstrated the enantioselective aminoalkylation, using chiral diamines as ligands. The introduction of chiral diamines in the metal complex produced the aminoalkylated products enantioselectivity with good ratio of enantiomeric excess. The plausible mechanism

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• , however, that the enantiomeric excess increases with an increase in bond length separation between the phosphorus and the R group. From the reaction evaluation we found that dual activation might be required from the catalyst in certain enantioselective reactions. Thus, CPA platforms that reintroduce a

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• HKR of epichlorohydrin with water was selected as a classical model to evaluate the catalytic activity of Co-unsymmetrical salen complexes 2e, 2f, and 2g for the asymmetric ring opening of epoxides. Enantiomeric excess (ee) results of 3-chloro-1,2-propanediol from the HKR reactions were summarized in

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

• integration, Figure 1B). Further improvement of the enantiomeric excess of 4 (90% ee, Figure 1C) was possible by performing the elimination reaction with 14 and KH and 18-crown-6 under ice cooling. This helped to suppress basic racemisation of 4, but required prolonged reaction times and gave a slightly

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• (+)-ximaocavernosin P [(+)-1]. Further, these isothiocyano-containing enantiomers were usually isolated as scalable mixture (where one enantiomer predominates) with an enantiomeric excess of ca. 80% [11]. In contrast, the two neutral cadinane-type enantiomers (4 and 5) were produced as racemic mixture (1:1 ratio

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• complex showed 23% enantiomeric excess in the asymmetric borane reduction of acetophenone in THF at room temperature (Scheme 33) [58]. The reaction of 3-(phenylaminomethylene)-2-phenylamino-6-methyl-2,3-dihydro-4H-chromen-4-one (213) and diethyl phosphite at 90–100 °C generated 2-ethoxy-6-methyl-2-oxo-1

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• kinetics [16][17][18], in enantiomeric excess [19], in stability [20], or in the position of the equilibrium [17][21]. State of the art for high-pressure research is the use of pressurized batch reactors [22][23]. Since continuous production and suitable reactors are receiving more attention [24], and some

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• on the reaction stereoselectivity. The cyclohexanediamine-linking macrocycles M1–M4 afforded the product with overall higher enantiomeric excess (ee) (Table 1, entries 1–4). Among which the isopropyl-substituted macrocycle M3 gave the best selectivity, i.e., 42% ee. This suggested a suitable crowding

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• series of 11 efficient enantioselective catalysts was tested to obtain the corresponding nitroaldol 21 in an enantiomeric excess as high as possible. Four of them based on the chiral ligands Ia, IIa, IIIa, and IV were identified as the most effective catalysts. They exhibited mutually comparable