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

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• under base-catalyzed conditions towards the formation of densely substituted dispirocyclopentanebisoxindole derivatives. The reaction proceeded in a diastereoselective manner to afford four chiral stereocenters. The method also has advantages of wide substrate scope, readily available starting materials

• diffraction analysis also revealed the presence of four chiral stereocenters with two oxindole moieties at 1,3-possition that are in trans orientation to the 2-benzoyl group and the 5-aryl group is in cis orientation (Figure 2). This observation proved that the most thermodynamically stable diastereomer was

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

• -opening reactions of heterobicyclic alkenes are of particular interest [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53], as they provide access to a broad family of synthetic building blocks bearing multiple stereocenters in a single step 2 [54]. Application of these functionalized

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• racemic codonopsinol B (1) and its N-nor-methyl analogue 2 starting from achiral materials. Four consecutive stereocenters in the target molecules were accomplished sequentially by the organocatalytic aza-Michael addition of N-Cbz-protected hydroxylamine to (E)-4-methoxycinnamaldehyde, the trans

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• ) appeared to be a more effective antiviral agent than AZT in PBM cells and U937 cells [13]. The BCH-189 core structure bears two stereocenters, and hence four stereoisomers are possible. The individual stereoisomers were also evaluated against HIV-1 activity in PBM cells and based on this study, it was

• anomeric center, which is governed by an anchimeric effect. Thus, the method determines the configuration of proximal as well as remote stereocenters in a single step, and both enantiomers of the β-nucleoside were accessed from affordable starting materials. Kashinath and co-workers [54] also identified an

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• hydrogenated brevipolide derivative. It is interesting to note that all the brevipolides A–J (1–10) pose the conserved stereocenters and bear a cyclopropyl unit in the core structure, which are in agreement with the prior structural assignment of compounds 7–9, previously identified as unnamed inhibitors for

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• halide anions can also engage as the nucleophile, which has been exploited in ring opening and related reactions (Figure 3b). In general, the idea of enantioselective ring opening produces two fixed stereocenters during one synthetic operation, increasing the complexity of the product significantly. This

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• White’s oxidation method as the final step in the first total synthesis of gracilioether F (75) [157], a natural polyketide with an unusual tricyclic core and five contiguous stereocenters, part of the family of gracilioethers 71–74 (Scheme 26A) extracted from the marine sponge Plakinastrella mamillaris

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• region on chromosome 6 [172]. Chemically, pyripyropene (PP) analogs are meroterpenoids containing a fused pyridyl α-pyrone moiety and eight contiguous stereocenters [170]. Metabolically, PPPA non-covalently binds within the fifth transmembrane domain of acyl-coenzyme A (CoA):cholesterol acyltransferase

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• three contiguous stereocenters in one single operation [59]. The utility of this approach is showcased in the enantioselective total synthesis of (+)-prelactones B, C, and V, as shown in Scheme 25. Yadav’s group reported the synthesis of 4-iodotetrahydropyrans (dr = 7.5:2.5) from aromatic aldehyde 111

• addition to construct a homoallylic alcohol, followed by Prins cyclization to furnish 2,3,4,5,6-pentasubstituted tetrahydropyrans 137 using β,γ-unsaturated N-acyloxazolidin-2-ones 134 as a key precursor [67]. In this Evans aldol−Prins (EAP) protocol, four new σ-bonds and five contiguous stereocenters were

• 302 and substituted aromatic aldehydes 303 to form hexahydro-1H-benzo[f]isochromenes 305 with three new contiguous stereocenters in high enantio- and diastereoselectivity [112]. The three new contiguous stereogenic centers formed resulted from an attack of the alkene to the Si-face of the oxocarbenium

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• , 12843 Prague 2, Czech Republic 10.3762/bjoc.17.58 Abstract Pyrrolidones are common heterocyclic fragments in various biologically active compounds. Here, a two-step radical-based approach to γ-lactams bearing three to four stereocenters starting from epoxides, N-allylic silylacetamides and TEMPO is

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• (inclusive). Keywords: all-carbon; cyclization; [3 + 2] cycloaddition; natural product synthesis; stereocenters; Introduction The highly-substituted, stereo-congested, five-membered carbocycle containing contiguous stereocenters is one of the most common structural features in many structurally complicated

• congested arrays of stereocenters within the polycyclic framework of complex natural products usually require a sophisticated synthetic planning. This issue is not trivial because only a few strategies are available for the efficient synthesis of such an intriguing molecular architecture. More importantly

• isoindigos to give an enantioenriched annulation adduct bearing vicinal quaternary stereocenters [46] (Scheme 7A). Both symmetric and unsymmetric isoindigos can undergo enantioselective [3 + 2] annulation with an allene and produced a chiral adduct with high yield and high ee value. When unsymmetric