Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• high (9:1 and >20:1), along with impressive enantioselectivity levels (92% and 98% ee). A slight loss of diastereoselectivity in the reaction of the PMP-imine with (Z)-crotyldioxaborinane 30 was attributed to the spontaneous isomerisation of the imine to the cis-isomer. The crotylboronates were

• synthesised from the respective cis and trans-butenes by deprotonation followed by reaction with triisopropylborate [27], therefore the presence of E isomer in the Z-product 30 cannot be excluded. Chiral BINOL-derived phosphoric acids have been known since the 1970s as industrially relevant chiral counterions

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• unprotected alcohol is tolerated in our procedure, with product 3l delivered at 50% NMR yield; 3l is sensitive to column chromatography, and thus aziridine-opening to a cyclic ether was observed (31% isolated yield) during purification. Aziridination of cis- or trans-4-octene afforded aziridine 3m as a 1.3

• :1.0 trans/cis mixture in 72% and 64% yield, respectively. While many styrene derivatives polymerize in HFIP [44], 1,2-disubstituted styrene derivatives were sufficiently stable to engage in the developed aziridination reaction, with cis- or trans-β-methylstyrene 1n furnishing aziridine 3n as

• diastereomeric mixtures with comparable yields of 38% (1.0:2.0 trans/cis, from cis-1n) and 35% (1.7:1.0 trans/cis, from trans-1n). Olefins containing N-heteroaromatics such as phthalimide and pyridine underwent aziridination to give 3o (32% yield) and 3p (26% yield). Similarly, 1,4-cyclohexadiene was compatible

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• compound 4a (Figure 2). These studies confirmed that R and Ar in the cyclohexane ring of compounds 3 and 4 are trans to each other and the Ar in the dihydropyran ring of 4 is trans to R and cis to Ar in the cyclohexane ring. The diastereoselectivity observed in the above cascade double Michael reaction of

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• molecules to create photosurfactants (PS), whose molecular shape and polarity can be modified using light [4][5][6]. Of the PS studied, most use an azobenzene (Azo) photoswitch that undergoes trans-to-cis (E-to-Z) isomerization on irradiation with UV light, typically forming a photostationary state (PSS

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

• ], respectively, while reference [68] provides UV-spectral data of both isomers. 1H, 19F, and 13C NMR data [69][70] are given in Table 2. Chemistry of HFO-1132 Isomerization Iodine-catalyzed cis–trans isomerization of 1,2-difluoroethylene and corresponding equilibrium measurements were described in the 1960s [47

• ]. Along with this, photoisomerization is described in patent literature [71][72][73][74]. It was shown that the experimentally observed enthalpy of isomerization (0.928 kcal/mol [47]) is in agreement with the calculated difference in the total energy of the two isomers (0.959 kcal/mol [65][75]). Cis-1,2

• cis-isomer decreases, i.e., the cis-isomer of 1,2-difluoroethylene is thermodynamically favored [47]. Deuteration The stereospecific reaction of (E/Z)-1,2-difluoroethylene with a 1–2 M solution of NaOD in D2O (90–120 °C, 2 d) led to the formation of CDF=CDF with high isotopic purity (Scheme 8) [76][77

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• subsequently set to 0 kcal/mol leading to the energy diagram in Figure 5. Two TSs leading to each product were found, all four of which utilized a coordinating Cs+ cation. The N1-s-cis and N1-s-trans TSs were the lowest in energy (27.5 kcal/mol and 29.1 kcal/mol, respectively), leading to two conformations of

• the N1-product with highly similar energy (averaging −16.8 kcal/mol). The N2-s-cis and N2-s-trans TSs leading to the N2-product were higher in energy and led to the higher energy N2 products. The critical difference between N1-s-cis and N2-s-cis is the presence of the N2–Cs+–O non-covalent interaction

• (NCI) in N1-s-cis, which accounts for the 2.1 kcal/mol difference in energy. Calculations showed that the sulfonate oxygens also chelate the cesium ion in both TSs. Thus, nitrogen NCIs with cesium, or lack thereof, seem to drive N1-product formation, which is both kinetically and thermodynamically

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• two diastereomers, lying in the intervals 5.5–6.0 Hz and 1.5–2.5 Hz for the cis and trans forms, respectively [33][34]. This makes it easy to assign the stereochemistry of the products obtained. Additional confirmation was gained from X-ray analysis data for structure 3t (Scheme 2). In some cases, we

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• to a trans-configuration because of the bicyclic carbon skeleton. Trifluoroiodane 3, on the other hand, has both trans- and cis-configurations of the fluorine ligands which could play a key role in the reductive elimination step in the fluorination of phenylmagnesium bromide. Trifluoroiodane 3 also

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

• their antiproliferative activity against a panel of cancer cells, in which the activity of some compounds was close to that of cis-platinum in some cell lines. It should be noted that N-propylamide derivatives showed low cytotoxicity on cancer cells. Additionally, 167c did not present cytotoxic activity

A fiber-optic spectroscopic setup for isomerization quantum yield determination

• Anouk Volker,
• Jorn D. Steen and
• Stefano Crespi

Beilstein J. Org. Chem. 2024, 20, 1684–1692, doi:10.3762/bjoc.20.150

• ]. Among the different switches known in the literature, azobenzene is a textbook example of a photoswitch operating via a double bond isomerization mechanism, with the first reports of its trans-to-cis interconversion under direct sunlight dating back to the work of Hartley in 1937 [2]. Over the decades

• spectra of the two isomers each show distinct bands, as shown in Figure 1. For trans-azobenzene, there is a π→π* band around 320 nm and a very weak (symmetry-forbidden) n→π* band around 440 nm. cis-Azobenzene shows two bands at 240 and 280 nm, and the n→π* transition is slightly more allowed than for

• trans-azobenzene [15]. As the bands of cis- and trans-azobenzene overlap, irradiation results in a photostationary state (PSS) which is a mixture of the isomers. The distribution of the isomers at the PSS differs for irradiations at different wavelengths [16]. Irradiation at 340–350 nm, where the ratio

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• the cis transition state TS4–Br (ΔG‡ = 16.1 kcal/mol), which yields the brominated nonaromatic intermediate I-6–Br in a highly exothermic step (ΔG = −52.3 kcal/mol). Finally, I-6–Br undergoes spontaneous aromatization, converting it into the experimentally observed 1-bromo-2-naphthol (P–Br), which is

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

• envelope of cyclopentane, with an NH unit occupying either a pseudoaxial or pseudoequatorial position (Figure 1a). When a hydrogen atom of the pyrrolidine at C-3 is replaced with fluorine, a conformational interconversion can occur within the cis- and trans-isomers, as illustrated in Figure 1b. The

• interactions [4]. Protonation of 3-fluoropyrrolidine generates the 3-fluoropyrrolidinium cation, and this typically results in a highly favored conformation in both the gas phase and solution where the fluorine and nitrogen atoms are cis, mirroring the behavior observed in analagous 4- and 6-membered ring

• delocalization is considered to be secondary [7]. However, stabilization via intramolecular hydrogen bonding does not seem to significantly impact the conformational stability of 3-fluoropiperidine. In this context, the cis-conformer, with the axial fluorine atom facing the N-hydrogen atom, is either equally or

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• yields (7a–e, 7g, and 7h), except for 6f which contained a methyl group at the 4-position. The reaction of 2,3-dimethylquinoline (6i) gave the desired product 7i (cis/trans = 3:1) in 77% yield. Substrates bearing acetyl (6k), ester (6l), and amide (6m) groups were tolerated under these conditions and

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

• stereochemistry. However, the reliability and applicability of these prediction methods have not been thoroughly assessed. In this study, we conducted a comprehensive bioinformatic analysis of 1,762 KR sequences from cis-AT PKSs to reevaluate the residues involved in conferring stereoselectivity. Our findings

• 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

• ), epothilone (anticancer), ivermectin (antiparasitic), and spinosyn (insecticide) [1][2]. Modular PKSs consist of multiple modules that catalyze one round of chain extension by domains with different functions and are divided into cis-acyltransferase (cis-AT) and trans-AT PKSs depending on whether AT domain is

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• dihydropyridine ring connects with the pyrrolidine ring in cis-position. The 4-aryl group exists on the trans-position to the 2,3-pyrrolidine ring. The methoxycarbonyl group in the ring of the cyclopentadiene stretches to the cis-position of the 4-aryl group in the dihydropyridine ring. Thus, it can be assigned

• can be performed with a wide variety of substrates. The molecular structure of the compound 6g was determined by single crystal X-ray diffraction method (Figure 2). The o-methoxyphenyl group exists on the trans-position of the fused pyrrolidine unit. The methoxycarbonyl group also exists on the cis

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• natural products containing a foundational 6/10-bicyclic framework and can be divided into two main classes, cis and trans, based on the configurations of their ring fusion at C1 and C10. Previous studies on two bacterial diterpene synthases, Bnd4 and AlbS, revealed that these enzymes form cis- and trans

• family members in bacteria and plants [4], these diterpenoids have four main structural differences: the number and location of oxidized carbons, the absence or presence of transannular ether bridges, the configuration (cis or trans) of the bicyclic ring fusion, and the presence and configuration (E or Z

• system and the C2–C3 alkene, are instilled by these terpene synthases. Four types of eunicellane synthases are known (Figure 1B). The first eunicellane synthase identified, Bnd4 from the biosynthesis of benditerpenoic acid in Streptomyces sp. (CL12-4) [5], forms a cis-eunicellane named benditerpetriene

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• case of compound 2p, unlike the other two compounds, the equilibrium is largely in favor of the product of interest and the NMR spectra confirm this. From the mechanistic point of view of the IMDAF reaction, the presence of both s-cis and s-trans conformations of maleamic acid intermediates in the

• reaction medium has been previously demonstrated by 1H NMR studies [129]. The elongation of the alkyl chain attached to the N atom facilitates the formation of the epoxyisoindole product by favoring the s-cis conformation due to steric factors (Thorpe–Ingold effect) [130][131]. Briefly, in this type of

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• presented in Tables S2 and S3 in Supporting Information File 1. Mean values are given respectively for the identical type of bonds and atoms. The differences in the double bond lengths are negligible, but the cis-1, cis-2, and e bonds are slightly shorter than the other bonds. The POAV values show no marked

• the transition state was ascribed to the donor–acceptor interactions between the HOMO of the silylene and the LUMO of ethylene, and vice versa [42]. For 2a, the LUMO is largely distributed at the e' bonds, followed by the cis-2 and trans-3 bonds (Figure 8). These results suggest that the formation of

• 3 may involve the interaction of 1 with the LUMO of 2a. The HOMO of 2a is observed mainly around the cis-1 and e′′ bonds among the 6,6-bonds, although the cis-1 bond would not be susceptible to the second silylene addition because of its steric hindrance. Alternatively, the interaction of the LUMO

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• ready-to-screen drug-like molecules remains a key challenge in the medicinal chemistry field [5][6]. Tetrazole is considered as a privileged scaffold in pharmaceutical and medicinal chemistry, used as a carboxylic acid bioisostere and a cis-amide mimic contributing to improvements in lipophilicity

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• 50% inhibition concentration of selected CYP450 enzymes (IC50). Cis-2,6-disubstituted [2]-ladderanes Brown and co-workers recently proposed cis-2,6-disubstituted bicyclo[2.2.0]hexanes ([2]-ladderanes) as isosteric replacements for meta-benzenes. An exit vector analysis indicated that the substituent

• . Isomerisation to the desired cis-[2]-ladderanes 150 was achieved through epimerisation of the ester functional group (Scheme 16B) [63]. Transformation of the phenyl group (of 150a) or alkene group (of 150b) into synthetically versatile acid 151 and protected alcohol 152 was achieved by standard chemical

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

• boron migration occurred during the hydroboration process of spiroviolene that resulted in the production of a mixture of 1α-hydroxyspiroviolane, 9α- and 9β-hydroxyspiroviolane after oxidation. The assertion of the cis-orientation of the 19- and 20-methyl groups provided further support for the revised

• , respectively. The formation of all three products 9–11 can be explained as follows (Scheme 2A) [28][29][30][31]: Due to the favorable formation of cis-5,5-fused B/C ring system, the borane reagent is preferred to approach the double bond of 1 from the α-face, to give either a secondary 1-organoborane

• suitable for X-ray diffraction [35]. The crystal structure of 13 clearly showed that the 19- and 20-methyl groups are cis-oriented in the D-ring which is consistent with that of spirograterpene A. This structural data reaffirms the revised structure of spiroviolene, and further support the unified

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• ][49]. Using liquefied HCl gas, he predominantly obtained cis-30 for the hydrochlorination of 1,2-dimethylcyclohexene (29) (Table 1, entry 1), while solutions of HCl gas in ether favored trans-30 (Table 1, entry 2). A similar study, though with lower selectivities, had been conducted by Fahey earlier

• [8]. In the presence of ammonium salts, a dilute solution of HCl in AcOH resulted in a 7:93 mixture of cis-30 and trans-30 (Table 1, entry 3), whereas an HCl solution in acetyl chloride produced a moderate 73:27 mixture (Table 1, entry 4). Grob also explored other bicyclic substrates such as

• octahydronaphthalene (31) and hexahydroindene 33 (Table 2 and Table 3). However, in the case of compound 31, the cis-selectivity was relatively low (Table 2, entry 1). Recently, Frøyen and Skramstad studied the hydrochlorination of 1,2-disubstituted alkenes with HCl gas (Scheme 6) [50]. Numerous unsuccessful attempts

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• categorized into the CCD subfamily and the 9-cis-epoxycarotenoid dioxygenase (NCED) subfamily. Five enzymes have been identified within the CCD subfamily: CCD1, CCD2, CCD4, CCD7, and CCD8. In animals, CCDs are involved in retinoid biosynthesis. In plants, CCD1 and CCD7 cleave the 9,10-double bond of

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

• depends on the relative configuration of the ligand used; cis-configuration of ligand affords the nitroaldols with major enantiomer S- (up to 97% ee), whereas the application of ligands with trans-configuration led to nitroaldols with major R-enantiomer (up to 96% ee). The “proline-type” ligand IV was

• improvement of enantioselectivity and the ee values obtained by its copper(II) complex were satisfactory (75–96%). This phenomenon was more distinct in the case of the application complexes of ligands with cis-trans configuration (Ib vs IIb). Whilst the complex of Ib exhibited only poor enantioselectivity

• , the other afforded the nitroaldols with ee values of 60–90%. Finally, the complexes of ligands with cis-cis configuration (Ic and IIc) were evaluated. These catalyst are the most efficient catalysts, producing nitroaldols with very high enantiomeric purity (approx. 90–95% ee). This finding contrasts

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• unusual methyl modification at the oxygen atom of the typical succinimide ring, a feature not seen in the structurally similar brocaeloid D. Additionally, shentonin A (1) exhibits a cis relationship between H-3 and H-4, as opposed to the trans configuration in brocaeloid D, suggesting a divergent