Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• standard conditions. Subsequently, radical-polar coupling between electrophilic Ni-bound α-carbonyl radical intermediate 45 and remaining nucleophilic Cu-enolate 44 provides a chiral product 42 containing vicinal quaternary stereocenters with high stereoselectivity, and all three possible stereoisomers of

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

• bifunctional squaramide-catalyzed asymmetric domino Mannich/formal [4 + 2] cyclization of 2-benzothiazolimines 21 with azlactones 15 [30]. Using cinchona-derived squaramide VII it was possible to obtain 25 different chiral benzothiazolopyrimidines 22 bearing adjacent tertiary and quaternary stereocenters in up

• isocyanide carbon, behaves a C3 synthon affording benzo[d]isothiazole 1,1-dioxide-dihydropyrroles 27 bearing two adjacent stereocenters in high yields (27–98%) and with moderate to excellent stereoselectivities (54–97% ee) when using thiourea IX (Scheme 10). The cyclization was observed with all derivatives

• methodology to synthesize interesting benzofuran-fused 2-piperidinol derivatives 29 and 31 bearing three adjacent stereocenters using squaramide X as organocatalyst (Scheme 11). Firstly, the reaction between azadiene 11 and trimethylsilyl dienolate 28 was explored obtaining 16 different derivatives in

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• , halogen bonding is an important interaction in biological systems [12][13][14][15][16][17] and the beneficial effect of the chloro substituent has been reviewed recently [18]. As a result, there is a lack of efficient synthetic strategies to access multivicinal inter-halide stereocenters (i.e., contiguous

• chiral halides: F, Cl, Br, I) [19]. Only a handful of natural product syntheses have been reported [20][21], despite the promising biological activity of these unique inter-halides [22]. For our part, we recently reported the synthesis of contiguous inter-halide-bearing stereocenters using a Chiron

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

• medicines such as erythromycin and rapamycin. They are often rich in stereocenters biosynthesized by the ketoreductase (KR) domain within the polyketide synthase (PKS) assembly line. Previous studies have identified conserved motifs in KR sequences that enable the bioinformatic prediction of product

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• diols by addition of water. For each of these intermediates, simple deprotonation or nucleophilic attack by water are possible. Also, hydride shifts can occur first, which widens the chemical space of possible products. Additionally, the presence of multiple stereocenters adds to the rich

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• stereoselective process to form complex terpene skeletons, normally with multiple stereocenters. In this context, the 3D-defined cyclization products retain the rich information of the complex cyclization process. Thus, assignment of the stereochemistry of the terpene skeleton with high confidence is crucial for

• stereocenters was elucidated on the basis of their NOESY spectra. Thus, the key NOE correlations of H-1/H-6, H-1/H3-19, and H-2/H3-20 of 9 allowed to assign the 1-OH to be α-oriented, while correlations of H-9/H-14 of 10, and H-9/H-3 of 11, supported the assignment of 9α- and 9β-oriented hydroxy groups

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• chemical shifts of allylic carbons [19]. Unfortunately, we were unable to determine the absolute configurations of Hya and three stereocenters in 4-amino-7-guanidino-3-hydroxy-2-methylheptanoic acid. ʟ-threo-Hya is reportedly present in 1, based on the elution order of FDAA (Nα-(5-fluoro-2,4-dinitrophenyl

• )-ʟ-alaninamide) derivatives [5]. In addition, a combination of NOESY and bioinformatics analyses proposed all three stereocenters of 4-amino-7-guanidino-3-hydroxy-2-methylheptanoic acid as S configured [5]. The stereochemistry of these moieties in 3–5 are discussed in the next section, regarding the

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• bicyclic cinmethylin (1) and methiozolin (2), substituted 1,8-naphthyridine 4 does not contain any stereocenters but still displays promising efficacy against grass weeds. Further considering the rather low molecular weight (220 g/mol) and structural simplicity, compound 4 is a highly attractive initial

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• ). Pioneering work by Schnermann and Overman demonstrated the early potential of photocatalytic Giese-type additions, successfully coupling two complex ring fragments and creating adjacent stereocenters, which effectively solved major challenges in the synthesis of (–)-aplyviolene [38] (Scheme 37A). Brown and

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• stereocenters [7]. In the Review paper by Kisszékelyi and Šebesta, the diverse variety of chiral metal enolates obtained by asymmetric conjugate additions of organometallic reagents and the possibilities to engage metal enolates in tandem reactions with new electrophiles are presented [8]. A Perspective from X

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• surface of carbon allotropes can increase diastereo- and enantioselectivity of Diels–Alder reactions. The direct formation of 1,3-nonadjacent stereocenters is a topic of concern in asymmetric catalysis [67]. To explore compatibility with anion–π catalysis, the addition of ethyl 2-cyano-2-phenylacetate (28

• selectivity generally increases with the polarizability of the carbon allotrope. Other reactions like asymmetric anion Diels-Alder reactions, the construction of 1,3-nonadjacent stereocenters and bioinspired ether cyclizations have been realized as well. The emerging combination with oriented external

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• 180,000 terpenoid compounds have been reported to date [1][2][3][4]. One of the most intriguing point is that all diversified structures are synthesized from common starting materials, isoprenoids. Reactions that generate complex cyclic structures and multiple stereocenters from linear achiral precursors

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

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• and co-workers (Scheme 72) [94]. Some of the characteristic features of this methodology are: enantioselective formation of the quaternary stereocenters, broad substrate scope, high enantioselectivity, and branched:linear selectivity. Furthermore, the NHC–Cu complex incorporating the chelating N-2

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• reaction for the synthesis of polyfunctionalized cyclohexenes bearing multiple stereocenters. The reaction is promoted by a chiral secondary amine, which is capable of catalyzing each step of the process activating the substrates through enamine and iminium ion catalysis towards a Michael/Michael/aldol

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

• groups into the aromatic ring. This reaction has a great scope of forming aza-stereocenters which can be tuned by different asymmetric catalysts. This review assembles recent advances in asymmetric aza-Friedel–Crafts reactions mediated by organocatalysts. The mechanistic interpretation with the origin of

• has the possibility of incorporating aza stereocenters into a product depending upon the choice of a suitable electrophile, i.e., imines. The present review assembled recent (from 2018 till date) examples of asymmetric versions of this important method mediated by different organocatalysts. The

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

• stereocenters were isolated in excellent yields and high diastereoselectivity. The authors have shown that catalyst loadings as low as 0.5 mol % can still be sufficient to promote the highly stereoselective reaction. Similarly to aldol reactions, Mannich-type additions are also suitable to trap the metal

• using acyclic enones 14 [27]. Their tandem conjugate addition/Mannich reaction methodology offers access to various non-cyclic β-aminoketones 16 with multiple contiguous stereocenters in high diastereo- and enantioselectivity (Scheme 5a). Additionally, chiral isoindolinones 18 and 2,3,4-trisubstituted

• the enolate intermediate in a cascade sequence, including borylation, aldol reaction, and finally oxidation (Scheme 36). The product 146 containing three consecutive stereocenters was obtained in a dr of 6.5 to 1 and with good yield and enantioselectivity. Lam and co-workers described a highly

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

• -catalyzed domino reactions of strained bicyclic alkenes, including both homo- and heterobicyclic alkenes. These compounds are important synthons in organic synthesis, providing an important platform for the construction of biologically/medicinally significant compounds which bear multiple stereocenters. The

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

• precluded the installation of the pyran ring – and the use of its well-known isomerization to set up important stereocenters [6][9] –, thus imposing the anticipated construction of key asymmetric centers. The following discussion will deal with the stereoselective synthesis of a stereopentade amenable to

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

• sesquiterpene with a unique framework. Indeed, this natural compound has a rare [6.3.0] carbocyclic backbone with a bridging butyrolactone, and possesses five cis stereocenters [39][40]. This compound, in a racemic version, has been studied by Krafft, Cheung and Abboud (Scheme 13) [39]. The initial strategy

• immunosuppressant. Structurally, variecolin (3) has a complex tetracyclic backbone with a fused [5-8-6-5] skeleton, with 8 stereocenters, 4 of them being contiguous and located on the C-ring [50]. The synthesis of the core structures of ophiobolin A (8) and variecolin (3) was undertaken by Gao and his group who

• ), 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

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• proceeds with the preservation of stereocenters. It is tolerant to a wide range of functional groups, which makes it compatible with natural substances and complex biologically active compounds. TEMPO and its derivatives are successfully used as electrocatalysts. 4-Acetamido-2,2,6,6-tetramethylpiperidin-1

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• through the corresponding lithium enolate occurred from the convex face of the bicyclic ring system [37]. After these two continuous stereocenters were successfully installed, the expected challenging all-carbon quaternary center at C1 was constructed utilizing the Nagata reagent (Et2AlCN). By using this

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• introduced in this study. Subsequently one equivalent of aldehyde and olefinic oxindole in situ were followed by decarboxylative 1,3-dipolar cycloaddition for diastereoselective synthesis of spirooxindolepyrrolothiazoles with generating 5 new bonds, 5 stereocenters and two heterocycles (Scheme 1C and Scheme

• diastereoselective spirooxindolepyrrolothiazoles by the formation of two new rings, 5 bonds, and 5 stereocenters without intermediate purification. To explore the reaction scope of 4-CR, different aldehydes 1 (Ar1) were used to react with ʟ-cysteine (2) and olefinic oxindole 4a in the synthesis of substituted

• stereocenters and two heterocycles in a diastereoselective fashion, and without intermediate purification. The one-pot four-component synthesis in green metrics analysis is compared with the stepwise reaction process to pinpoint the overwhelming advantages of the one-pot approach in the CE, MP, PMI, and SI by

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

• present in the 1H NMR spectrum in each case). Assigning of the relative configurations of newly formed α- and β-stereocenters in cysteine derivatives discussed above was performed using the NOESY spectra. It is illustrated in Figure 4 taking complex 10 as an example. A correlation between protons of the

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

• as starting materials, realizing an unprecedented asymmetric induction in the synthesis of cyclohexadiene-fused γ-phosphinolactams 126–131, through the formation of configurationally stable lithium salts. When aldehydes 125 were applied as electrophiles, three new stereocenters were generated in the