1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• Haszeldine et al. [49][100]. The reaction of individual E- or Z-isomer of 1,2-difluoroethylene and fluorinated ketones (Scheme 21) led to a mixture of stereoisomers in both cases, although for the E-isomer, about 70% of the product retained the starting configuration. Overall, (E)-1,2-difluoroethylene had

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• course of an extensive screening of NMDA (N-methyl-ᴅ-aspartate) channel blockers resembling 1,2-diphenylethylamines. A channel pharmacophore description was envisaged collecting data from stereoisomers of 1,2-diphenylethylamine derivatives and 1,2-dicyclohexylethylamine derivatives. Among them, isomer (S

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• compared to the stereoisomers 75, with enhanced activity observed upon substitution of the aromatic ring. Interestingly, hydrolysis of the acetate group on C-3 did not significantly affect the antiproliferative effect, indicating that the activity is primarily influenced by the stereochemistry and

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• crystallographic data using the 3-fluoropyrrolidinium cation and 3-fluoropyrrolidine. Subsequently, we explored the relative energy of all favored conformations of all different stereoisomers of 2,3-, 2,4-, and 3,4-difluoropyrrolidines at the B3LYP-D3BJ/6-311++G** level. A generalized anomeric effect, arising from

• stereoisomers to influence preferred conformations when designing functional molecules. Experimental Computational details The benchmark study was conducted for 3-fluoropyrrolidine and 3-fluoropyrrolidinium cation to determine the optimal theoretical level for further investigations involving 2,3-, 2,4-, and

• (nN→σ*CF anomeric and σCH→σ*CF fluorine gauche effects) on the conformation of different stereoisomers is explored. MAE comparing the geometry parameters (bond length, bond angle, and dihedral angle) obtained from DFT calculations at the CCSD/DGTZVP level. The MAE for the crystal structure compared to

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

• C6 position of the C6–C7 double bond leads to 4 distinct 6-6 bicyclic cationic stereoisomers (A–D, Figure 1). Reprotonation at the C3-position of the C2–C3 double bond forms 6-6 bicyclic compounds that are not observed in nature for eudesmanes as they proceed via a secondary carbocation [16

• moving in the order of increasing ring size (i.e., 5 to 6 to 7), we observe an increase in the standard deviation (variation in the difference in energy among the different stereoisomers). In case of the 6 membered (A–D), 7 membered (E–H) and 5 membered ring (I–L) cations, the standard deviations in

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• substrates, MSTSs can also accept partially cyclized substrates. A class I diterpene synthase SiTPS8 from Setaria italicais is capable of utilizing three copalyl pyrophosphate (CPP) stereoisomers that were generated by different class II TSs, including ent-CPP (19), (+)-CPP (20), and syn-CPP (21), to

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• , producing the vicinal N-heterocycle-substituted olefin 9 as a mixture of stereoisomers in 65% yield. Finally, 4aa proved to be a viable nucleophilic VBX for the carboiodanation of 3-methoxybenzyne [35], furnishing the new ortho-alkenylated arylbenziodoxole 10 with exclusive C–C bond formation at the distal

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• , although 11a was sufficiently stable for filtration through a pad of silica. Applying these conditions and isolation protocols to all 3,3-disubstituted alcohols 10c–f gave moderate to excellent yields of the rearrangement products 11c–f as single stereoisomers. The reactions of alcohols 10b,d,e also gave

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• stereoisomers, ent-CPP and syn-CPP. Class II TCs can also generate further structural diversity through hydride shifts, methyl shifts, and/or skeletal rearrangement of the labdadienyl+ diphosphate intermediate which is formed by the initial bicyclization. Following this class II TC-mediated cyclization, class I

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

• derivatives possess similar enantioselectivity. However, compound IV is less catalytically active, probably due to the lower acidity of protonated 1H-imidazole than 1H-tetrazole [17]. Conclusion In this study, we successfully synthesised enantiomerically pure stereoisomers of 2,2'-(pyridin-2,6-diyl)-bis

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• signal at −12.4 (5a) and −13.5 ppm (5b), which clearly indicated that the Li+ was encapsulated in the highly shielded inner space of the fullerene cage. The observed chemical shift was almost identical to that of reported Li+@C60 derivatives [10][12][24]. Although the product 5a may have stereoisomers

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• of stereoisomers in 2:1 ratio. After isolation by distillation, 2,3-dibromo-1,1,1,4,4,4-hexafluorobutane (2) was characterized by 1H, 19F, 13C NMR and mass spectra. We studied the reaction of dibromoalkane 2 with various bases such as DBU, Hünig’s base (iPr2NEt), and potassium hydroxide (Table 1). In

• showed a mixture of stereoisomers with a 2:1 ratio. The dehydrohalogenation reaction of 2-chloro-3-iodo-1,1,1,4,4,4-hexafluorobutane (5) was studied. Like the dehydrobromination of alkane 2, the reaction of compound 5 with 1.3 equivalents of KOH in water in the presence of 5 mol % of Bu4NBr was carried

• , product 16 represented a mixture of stereoisomers in 2:1 ratio. After isolation by distillation butane 16 was characterized by 1H, 19F, 13C NMR and mass spectra. The reaction of alkane 16 with DBU in pentane as a solvent led exclusively to dehydrobromination with the formation of a mixture of (Z)- and (E

GlAIcomics: a deep neural network classifier for spectroscopy-augmented mass spectrometric glycans data

• Thomas Barillot,
• Baptiste Schindler,
• Baptiste Moge,
• Elisa Fadda,
• Franck Lépine and
• Isabelle Compagnon

Beilstein J. Org. Chem. 2023, 19, 1825–1831, doi:10.3762/bjoc.19.134

•  1b, featuring three stereoisomers of C8H15NO6). With the rapid development of our approach, such method now reached a high data output since a single IR fingerprint can be obtained in few seconds. The fast and automatic identification and classification of the data becomes compulsory, which motivates

• ion trap mass analyzer. The following monosaccharides were analyzed: three stereoisomers of hexosamine of chemical formula C6H13NO5, namely glucosamine (GlcN), galactosamine (GalN), mannosamine (ManN); and N-acetyl glucosamine (GlcNAc, chemical formula C8H15NO6). One typical spectrum of each of the

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• that the geometry of the intermediate bis-amidrazone C facilitates macrocycle 5 formation. The DFT B3LYP/6-311++G(d,p) calculations of ten different tautomers and stereoisomers of bis-amidrazone C (DMSO and MeOH solutions) revealed that the structure shown in Scheme 6 is the most stable. Clearly, the

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

Bromination of endo-7-norbornene derivatives revisited: failure of a computational NMR method in elucidating the configuration of an organic structure

• Demet Demirci Gültekin,
• Arif Daştan,
• Yavuz Taşkesenligil,
• Cavit Kazaz,
• Yunus Zorlu and
• Metin Balci

Beilstein J. Org. Chem. 2023, 19, 764–770, doi:10.3762/bjoc.19.56

• configurational assignment of organic compounds. The experimental NMR data (13C NMR chemical shifts) are compared with those predicted for all possible theoretical stereoisomers. The correct stereochemistry may be obtained by combining the computed and experimental data [1]. Recently, Novitskiy and Kutateladze

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

• were able to isolate product (+)-214 in good yield (75–85%) and excellent stereoselectivity (>95%) on a multigram scale. Additionally, both stereoisomers are available by simply using the ligand with the opposite stereochemistry. Pleuromutilin-based antibiotics are an essential line of defense in the

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• trans isomer (diastereomeric ratio 1.4:1). Moreover, although Int4 is the overall thermodynamic minimum of the reaction for all stereoisomers, it is still unsurprising that the reaction proceeds towards the product since the abstraction of the catalyst is the last step. Once abstracted, the catalyst is

• Int2 yielding Int4_3 and Int4_4 without further intermediates. Formation of the products Pr1 to Pr4. Optimization of the reaction conditionsa. Change in Gibbs free energy ΔG (kcal∙mol−1) from the CuI-catalyzed cyclopropanation of the diazo compound with styrene for possible stereoisomers Pr1 to Pr4

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

• was not controlled, yielding a mixture of stereoisomers. Recent developments were undertaken to propose an asymmetric version [56][57]. In its intramolecular version, the NHK reaction was successfully applied by Kishi in 1989 to forge the cyclooctane ring of ophiobolin C (30) [5-8-5] framework, thus

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• -cyclisation to the (Z,E)-germacradienyl cation (E) or a 1,11-cyclisation to the (Z,E)-humulyl cation (F), the E/Z stereoisomers of B and C. Furthermore, a 1,6-cyclisation to the bisabolyl cation (G) or a 1,7-cyclisation to H may follow, which is not possible from A because of its 2E configuration (a

• reprotonation at C-1 of 1, leading to four different stereoisomers of cation I, i.e., I1 with a trans-decalin skeleton, its enantiomer I2, I3 representing the cis-decalin skeleton, and its enantiomer I4 (Scheme 6A). In principle, the eudesmane skeleton can also be formed through cyclisations induced by

• reprotonation at C-4. Assuming anti addition to the C-4/C-5 double bond, these reactions lead to four stereoisomers of the secondary cation J, two with a trans-decalin skeleton (J1 and J2) and two with a cis-decalin skeleton (J3 and J4). However, no natural products are known that may arise through any of these

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• amorph-4-ene-10β-ol known from plants. A short synthesis using an organocatalytic approach through a tandem Mannich/intramolecular Diels–Alder reaction led to a mixture of cadinols, which was used for the assignment of the natural cadinol structures and their stereoisomers. Keywords: Anura; chiral gas

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• excess of a perbenzoic acid, as shown for the oxidation of 6 to 7 [33][34]. Partial oxidations are also possible, but lead to mixtures of sulfoxides, including cis- and trans-sulfoxide stereoisomers (see also chapter 6). For a more detailed and extensive discussion of the synthesis of 1,4-dithiin

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• ; stereoisomers; Introduction Calculation of 1H and 13C NMR chemical shifts and coupling constants using density functional theory (DFT) has increasingly become an adjunct to structure determination [1][2][3][4][5][6][7][8]. In particular for complex organic compounds, determination of relative stereochemistry

• . Calculated 31P NMR chemical shifts for stereoisomers and unusual structures. We next chose our own set of phosphorus compounds (Figure 5, 11–29; for simplicity compounds 30–34[O] discussed later are included in the MAD/RMSD values here). This was done to to determine if the calculation and scaling would be

• accurate enough to distinguish stereoisomers via chemical shifts rather than coupling constants [72][73] and provide confirmation of unusual structures and chemical shifts, and with the further stipulation that multiple P–C bonding would likely give inaccurate M06-2X NMR calculations (Table 3; results with

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• pressure. Purification by column chromatography (5% Et2O/pentane), gave 19 as a colourless oil (866 mg, 94%, 91/9 mixture of stereoisomers). Analytical data were in agreement with literature data [18]. (2R,3S,6RS)-3-Ethyl-2-((E)-2-iodovinyl)-6-methoxy-3,6-dihydro-2H-pyran (20): This compound was prepared

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

• well as the previously synthesised HTM222 (2) and 1 isolated from S. spectabilis. Neither 2 nor any of the stereoisomers of 4 showed antibacterial effects against a panel of Gram-positive and Gram-negative organisms (Supporting Information File 1, Table S2). Only 1 exhibited concentration-dependent