Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• functionalized oxazolidine derivatives in moderate to good yields and good to excellent enantioselectivities and high diastereoselectivities. The stereocontrol was rationalized in the proposed reaction mechanism. Experimental Unless otherwise noted, all materials were purchased from commercial suppliers. Toluene

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• , the terminal alkene remains intact during this process, and the initial protonation proceeds with full stereocontrol, rendering this transformation both highly chemo- and diastereoselective. From the cyclization result, it is presumed that the higher nucleophilicity of the alkyne functionality over

• elegant [2 + 3] cycloaddition of secondary enecarbamates [28], the extension of this reaction to enamides lacking an N–H group is a notable advancement. After extensive optimization, the chiral dirhodium catalyst cat. 1 was found to be most capable in terms of both stereocontrol and efficiency. The use of

• cases, the use of a chiral Cr(III)(salen)Cl complex in combination with InCl3 was necessary to maintain a high level of stereocontrol. Total synthesis of (−)-cephalocyclidin A The bicyclic and tricyclic N-heterocycles without a fused arene are essential core structures in a wide array of alkaloids. A

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• examples of amino-sulfonoxylations using tethered nitreniums. Putative reaction mechanism. (A) Scale-up and (B) applications. Optimization results. Structure–reactivity relationship with nitrenium tethers. Examination of sulfonic acid scope. Substrate scope exploration with an emphasis on stereocontrol and

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• C(sp3)–C(sp3) coupling via distal stereocontrol, efficiently producing C3-alkylated pyrrolidines, while the nickel catalytic system afforded C2-alkylated pyrrolidines through a tandem alkene isomerization/hydroalkylation process. This method utilized readily accessible catalysts, chiral BOX ligands

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• stereocontrol (Scheme 1b) [24]. In 2023, Zeng et al. reported the first example of a chromium-catalyzed spirocyclization between anilines and cyclobutanones, providing direct access to medicinally relevant cyclobutane-annulated and structurally constrained spirotetrahydroquinoline (STHQ) scaffolds [25]. Given

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

• complete stereocontrol. For example, the reaction of syn-alkylcopper species 14 with 3-methylbut-2-en-1-yl bromide (15) provided the corresponding SN2 product 16 in excellent yield and stereoselectivity (SN2/SN2' = >99:1, dr = 97:3). Remarkably, the regioselectivity of these reactions could be completely

• [58]. This methodology has emerged as a powerful strategy for constructing stereogenic centers with high levels of stereocontrol, offering important complementarity to established CuH-catalyzed processes. While CuH-catalyzed processes have proven highly effective for numerous substrates, they exhibit

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• achieve better stereocontrol and to facilitate the formation of synthetically challenging glycosidic linkages. Keywords: chemical O-glycosylation; neighbouring group participation; remote group participation; solvent effect; stereocontrol; Introduction Cell surface glycans in living cells have

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

• organocatalyst C21. A considerable drop in yield and enantioselectivity was also observed in the reaction with dibenzylaniline. Interactions with and steric effects of the CPA C21 guiding the orientation of the substrates dictate the stereocontrol of the reaction. The utilization of CPA (R)-C23 in a dynamic

• , bearing both axial and central chirality, were prepared by organocatalytic asymmetric addition of bisindoles 145 and isatin-derived imines 146 catalyzed by CPA C26 (Scheme 43) [71]. The scope of the reaction showed efficient stereocontrol by consistently high diastereo- and enantioselectivity with

• . Experiments determining the configurational stability were done in both toluene at 120 °C and o-xylene at 150 °C for up to 36 h with retained stereoselectivity but decreasing yields at higher temperatures for prolonged periods of time. The possible activation mode explains the stereocontrol of the reaction

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

• , followed by a Conia-ene cyclization. The absolute configuration of the products is controlled by the ligand, which further confirms the remote stereocontrol of the copper catalyst. They obtained a single crystal of dinuclear copper and confirmed that the catalytic efficiency of the single crystal is

• of ortho-aryl steric hindrance. Recently, Xu et al. [81] presents a copper-catalyzed asymmetric [4 + 1] annulation strategy, utilizing remote stereocontrol substitution/annulation/aromatization to forge arylpyrroles with various C–C (Scheme 49, 48a–h), C–N (Scheme 50, 49a–h) or 1,2-di- (Scheme 51

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

• more precise stereocontrol of the reaction [128][129][130][131][132]. Therefore, the difference in enantioselectivity values may be attributed to these electronic effects. Ultimately, the most favourable outcomes were achieved with catalyst C30 at 0 °C, with yields reaching up to 84% and enantiomeric

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• stereochemical outcomes of KRs. These updated fingerprint motifs for stereochemical prediction not only enhance our understanding of the enzymatic mechanisms governing stereocontrol but also facilitate accurate stereochemical prediction and genome mining of polyketides derived from modular cis-AT PKSs. Keywords

• : bioinformatics; conserved motifs; ketoreductase; polyketide synthase; stereocontrol; Introduction Type I modular polyketide synthases (PKSs) are large enzyme complexes that play a crucial role in the biosynthesis of bacterial polyketides, including many important clinical drugs such as erythromycin (antibiotic

• substrate contains an α-substition. Subtype 1 (A1, B1, and C1) KRs retain the original α-ᴅ-configuration, while subtype 2 (A2, B2, and C2) KRs epimerize the α-carbon to yield α-ʟ-configured products (Figure 1b). The stereocontrol of KR has been found to correlate with several conserved sequence motifs

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• chair–chair stereocontrol, the structure basis of InsA7 should be unique. A structural comparison of InsB2 and InsA7 will help to clarify the differences in their structural bases. Recent advances in artifical intelligence (AI) have even made the structural modeling of membrane-bound proteins possible

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• 5 and 8a in 77–88% yields, albeit as poorly selective mixtures of diastereoisomers. This lack of stereocontrol is not surprising, given the well-known difficulty to control the relative configuration between the two adjacent stereocenters created during aldol condensations with zinc enolates

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

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

• stereocenter in cyclic sulfamidate derivatives. N-Alkyl and N-benzyl-substituted pyrroles responded to the process with appreciable enantioefficiency. However, pyrrole was not proved to be the efficient substrate in terms of stereocontrol [27] (Scheme 4a). In the very next year, pyrrole was successfully

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

• Indonesian sponge Haliclona sp. [108]. Their synthesis takes advantage of the same tandem procedure that gives β-ketoester 219. The asymmetric conjugate 1,4-addition and subsequent acylation provided good stereocontrol and the authors could revise the thus far incorrectly assigned configuration of the target

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• analogue synthesis, starting from (+)-β-citronellene. Key stereoselective transformations involve an asymmetric Krische allylation, an aldol reaction under 1,5-anti stereocontrol, and a Tishchenko–Evans reduction accompanied by a peculiar ester transposition, allowing to install key stereogenic centers of

• the natural products. Keywords: allylation; aldol reaction; latrunculins; stereocontrol; total synthesis; Introduction Latrunculins constitute a class of marine polyketide natural products isolated from Sponges like Negombata (= Latrunculia) magnifica [1][2]. They are characterized by the presence

• formed by the oxidation of an allyl moiety introduced by the asymmetric allylation of an aldehyde derived from (+)-β-citronellene. At this stage, we can speculate that the stereocontrol of this reaction could either follow a polar Felkin–Anh model [14][15][16] based on chiral aldehyde partner 8 [17], or

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

• ), where the eight-membered ring was accessed through a SmI2-mediated cyclization cascade reaction of a dialdehyde [69]. In this approach, an original way was proposed to form in a single step the tricyclic core of pleuromutilin (1) with a stereocontrol at the four contiguous stereocenters [69][70]. The

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• electrocyclization of compounds 1a and b [19][20][21][22]. Interestingly, Baldwin and Moses demonstrated the irradiation or sunlight-promoted cycloisomerization of a similar tetraenyl framework into the bicyclo[3.1.0]hexane core through a 6π-conrotatory stereocontrol [23][24]. To date, the known strategies to

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• communication in the microbial world. Herein, we report the solid-phase total synthesis and structural confirmation of longicatenamide A. First, commercially unavailable building blocks were chemically synthesized with stereocontrol. Second, the peptide chain was elongated via Fmoc-based solid-phase peptide

• with stereocontrol. Then, the peptide chain was elongated by Fmoc-based solid-phase peptide synthesis. Finally, the cyclization of the peptide chain followed by simultaneous cleavage of all protecting groups in the solution phase afforded target compound 1. The comparison of the chromatograms of

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• and stereocontrol of the reaction depends on the conformational rigidity of the macrocyclic framework and a synergy between the thiourea and tertiary amine sites. Recently, many efforts were focused on the synthesis and applications of mechanically interlocked molecules (MIMs), such as catenanes and

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• base platform creates an optimal balance between the covalent binding with the substrate (which does not “kill” its reactivity but precludes its redox destruction) with non-covalent interactions in the metal chiral coordination environment governing the reaction’s stereocontrol. Cyclic voltammograms

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

• tertiary amine sites were found to be crucial for achieving efficient activation and stereocontrol. As shown in control experiments, catalysis with the acyclic analogues having the same structural motifs were non-selective. Keywords: chiral macrocycles; cooperative asymmetric catalysis; decarboxylative

• cavity environment may be good for stereocontrol. The diphenylethylenediamine-linking macrocycles M5 and M6, however, gave very low ees (Table 1, entries 5 and 6). The hetero-macrocycles M7–M12 did not afford better selectivity as well (Table 1, entries 7–12). It is interesting to note that M9–M12 led to

• stereocontrol. On the other hand, compound 3c led to a much slower conversion and also nearly racemic product formation, indicating that the thiourea units must have engaged in activation and being cooperative with the tertiary amine sites. With the reaction outcomes and pronounced macrocyclic effect observed

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• catalyzed by rhodium/diene to afford the 1,2,4-trisubstituted naphthalene framework 8 with complete regio- and stereocontrol (Scheme 1) [62][63]. In 2015, the Nishimura group reported the first iridium-catalyzed addition of salicylaldehydes 14 to bicyclic alkenes 11 (Scheme 1) [64]. Although a variety of

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• and could considerably improve the stereocontrol of the reaction [21]. The axially chiral arylquinazolinones form the backbones of a large number of natural products and biologically active compounds as well as chiral ligands [83]. Nevertheless, a simple chiral phosphoric acid-catalyzed

• gram scale was carried out without loss of chemical yields and stereoselectivities under optimized conditions. The authors also found that the excellent stereocontrol was due to the simultaneous interaction between the bifunctional phosphoric acid and the intermediate formed in the reaction via