Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• observed (Figure 6). As with the oxidation, we assume that the lower deck blocks approach from one face. Protonation of the adduct also occurs anti to the para ring. We suspect that this second addition favors the trans product over the cis rather than the para ring influencing the approach of the proton

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• to the formation of the expected 4-(3,4-dimethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-2-ol (14aa), 51:49 mixture of cis/trans-diastereomers) as a colorless oil in 50% yield (Table 1, entry 1). The use of Et2AlCl as the Lewis acid gave tetralin 14aa in a slightly improved 55% yield (Table 1, entry 2

• substoichiometric amounts afforded significantly decreased yields of 14aa (Table 1, entries 7 and 8). The relative cis- and trans-configuration of the C-2 hydroxy group and the C-4 aryl substituent (Figure 2) were assigned on the basis of 1H-1H COSY analysis. Firstly, the HSQC analysis was used to determine H3. The

• 13C NMR chemical shift for C2 is expected to be in the range of 60 to 70 ppm and the assignment of H3 was based on the HSQC correlation between H3 and C2. Then, H1 and H2 could be assigned by COSY and HSQC experiments. Following that, NOE analysis was applied to analyze the relative cis- and trans

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• smoothly occurs to give alkynes 4 because substituent R1 can readily approach the C–Cl antibonding orbital (Scheme 7a). On the other hand, when substituent R1 is located cis to the chloro group and a nonmigratable alkyl group R2 occupies the trans position, the 1,2-rearrangement does not occur directly

• alkynes 4. a) 1,2-Rearrangement readily takes place with substrates with trans-oriented Cl-substituent to the migratable group R1. b) Formation of product 4 from geometric cis isomer is possible due to the equilibrium between magnesium alkylidene carbenoids. c) Halogen exchange between a 1-chlorovinyl p

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• and restless leg syndrome [53]. Guareschi imides exist in solution predominantly as dicarbonyl tautomers with a cis arrangement of the cyano groups. Conversely, the corresponding anions exist as a mixture of mono- and dienolized tautomers, with a strong preference (≈9:1) for the monoenolized form [8

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• cyanomethylarylation of N-aryl acrylamides for the synthesis of oxindoles. Reaction conditions: 7 (0.2 mmol, 1 equiv), 2d (0.4 mmol, 2 equiv), CH3CN (8 mL), CN-K (0.5 mg/mL), 2 × 24 W blue LEDs (460 ± 5 nm), 80 °C. aConducted at 100 °C. bPerformed with 1 mg/mL of CN-K. cRatio = trans/cis. CN-K-catalyzed

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• -bromoenolates to enantiopure p-toluenesulfinamide 5. cis-aziridine 7a was formed as the major diastereoisomer in 89% yield and the trans-isomer in 8% yield in a one-step procedure using lithium enolates of methyl bromoacetate 6a and sulfinyl imine 5. Lithium enolates of methyl α-bromopropionate gave trans

• -aziridine in 50% yield under the same conditions. The transition state is proposed with a six-membered chair-like transition containing a four-membered metallocycle. In cis-aziridine the enolate of methyl α-bromoacetate has E-geometry and the trans-aziridine 8a has Z-geometry [32][33]. In the transition

• -tribromomethylamines 16. The structure and configuration of aziridines 15 were determined unambiguously by single crystal X-ray analysis [64]. In order to explain the experimental results, a nonchelation controlled transition state was proposed. Based on computational studies, it is known that a kind of s-cis

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• donors for the installation of a 1,2-cis-linked multifluorinated GlcNAc and GalNAc moiety. Results and Discussion Our approach to the synthesis is summarized in Scheme 1. Challenging regio- and stereoselective introduction of fluorine at C3 and C4 of the pyranose ring, together with azide installation at

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

• ion intermediate in a stereoselective manner for THP ring formation as shown in Scheme 3. The outcome of exclusive cis-stereoselectivity in the Prins cyclization might be attributed to the most favorable conformation adopted by 12 with equatorial orientation of the 2,6-substituents (R1 and R2). Alder

• and co-workers explained the formation of all-cis-2,4,6-trisubstituted THPs with the help of density functional theory (DFT) and stated that in the presence of an external nucleophile, the stabilization of the carbocation intermediate is favored through hyperconjugation [28]. The vacant p-orbital of

• -orbital at C4. These orbital stabilizations, along with the lack of 1,3-diaxial interaction experienced by the incoming nucleophile (mostly halide) leads to the preferential equatorial attack over an axial attack by the nucleophile (Scheme 3) to give all-cis-2,4,6-trisubstituted THPs. In the absence of an

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• transfer takes place, giving radicals 33 and 34. Radical 34 is quenched by oxygen, and radical 33 attacks 31 in order to form radical 35. Intermediate 36 is achieved by cyclization of radical 35, followed by hydrogen-atom removal, providing the cis-tetrahydroquinoline 32 (Scheme 11). It is worth noting

• , including cis-fused pyrrolo- and furanoindolines. The X-ray single-crystal analysis showed that the EDA complex is received in the form of a face-to-face π–π complex, and the ratio of donor to acceptor is 1:1. In the same year, based on previous experimental phenomena and data, Melchiorre and colleagues [45

• perfluoroalkylated pyrimidines 26 initiated by an EDA complex. Synthesis of phenanthridine derivative 29 initiated by an EDA complex. Synthesis of cis-tetrahydroquinoline derivative 32 initiated by an EDA complex. Mechanism of the synthesis of cis-tetrahydroquinoline derivative 32. Synthesis of phenanthridine

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• Emine Salamci Yunus Zozik Department of Chemistry, Faculty of Sciences, Atatürk University, 25240 Erzurum, Turkey 10.3762/bjoc.17.59 Abstract The efficient synthesis of two new stereoisomeric 3-aminocyclooctanetriols and their new halocyclitol derivatives starting from cis,cis-1,3-cyclooctadiene

• are reported. Reduction of cyclooctene endoperoxide, obtained by photooxygenation of cis,cis-1,3-cyclooctadiene, with zinc yielded a cyclooctene diol followed by acetylation of the hydroxy group, which gave dioldiacetate by OsO4/NMO oxidation. The cyclooctane dioldiacetate prepared was converted to

• of two new 3-aminocyclooctanetriols and some chlorinated C8-cyclitols starting from cis,cis-1,3-cyclooctadiene. Results and Discussion For the synthesis of amino- and chlorocyclitols and their derivatives, we first selected endoperoxide 5 as the starting molecule, which was prepared using a procedure

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

• lactams 12a–k in 66–93% yields. The thermal cyclization of α-(aminoxy)amide 9a provided two diastereomers of lactam 12a in a 2:1 trans/cis ratio (Table 3, entry 1). The N-allylic amides 9b–f provided lactams 12b–f as mixtures of four inseparable diastereomers in which those with trans orientation of the

• substituent at the nitrogen atom also plays essentially no role for the diastereoselectivity of the cyclization (Table 3, entry 10 vs entry 9). The minor cis-diastereomer of N-(1-β-naphthylethyl)pyrrolidone 12j crystallized after oxidation to ketone 13j and its configuration was unequivocally established by X

• -ray crystallography (Figure 3, vide infra). Similarly, the minor cis-diastereomer of hydroxy lactam 12k crystallized and its configuration was confirmed. The configuration of the other lactams was assigned by analogy, by base-mediated equilibration and oxidation experiments (vide infra). The α

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• cosmetics [147]. The catalyst could be recycled, however, with reduced performance due to Pt nanoparticle oxidation. 3.1.2 Polybutadiene (PBD): Partial depolymerisation of 1,4-PBD (cis, trans, Mw 1800–500000 g⋅mol−1) was achieved by an unconventional tandem ring-opening–ring-closing metathesis route

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• to its toxicity, the oxidation rate affording trans-diols was very slow in comparison to that for cis-diols. Using an even longer reaction time and stoichiometric amount of the reagent, diol 5 was not oxidized to the corresponding dicarbonyl compound 8. However, using NaOCl·5H2O as an oxidant [31

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• conversion of oxanorbornene (rac)-13 to heterotricycle (rac)-16 through the eight-membered-ring formation would be owing to the cis-relationships of the pentenyl and vinyl groups on the ring B of (rac)-15, which allows the proximal arrangement of the reacting sites in the RCM. The N-Boc derivatization of

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• and cis isomers of 2-hydroxy-2-oxo-3-[(phenoxyacetyl)amino]-1,2-oxaphosphorinane-6-carboxylic acid (16, Figure 3) were prepared and evaluated as inhibitors of the zinc-containing β-lactamase II from B. cereus. However, neither stereoisomer had any significant activity [6]. The phosphonodepsidipeptide

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• featured in proline residues as well as the high conformational stability of the trans- and cis-amide conformers assign proline another important structural role: the structure freezer. The incorporation of proline residues in connecting loops has been described as a general strategy towards the

• proline is the comparatively similar intrinsic stability of the amide rotamers in the peptidyl-prolyl fragments. Usually, a peptide bond exhibits a high preference towards the trans-amide, represented by a dihedral angle ω of 180°. In peptidyl-prolyl, however, trans- and cis-conformations (ω = 180° and 0

• °, respectively) are of comparatively similar stability, while the trans-amide is more stable (Figure 7) [53]. In a folded protein, the overall conformation dictates the amide rotation state. Nonetheless, when the protein is unfolded, the trans/cis isomerism can create numerous subpopulations, and the resulting

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• )cadmium (51) precipitates quantitatively as a white powder from the reaction of CF3I with Cd(Et)2 (molar ratio 2.5:1) (Scheme 21) in chloroform at −40 °C. A warming to −5 °C was sufficient to liberate difluorocarbene, which was trapped by the addition to alkenes. Thus, cis-stilbene (52) gave the gem

• hydrogenation of difluorocyclopropenes [73][79]. Enzymatic hydrolysis or esterification: The first example of the enzymatic resolution of gem-difluorocyclopropanes was reported by Itoh et al. [80]. The prochiral diacetate of cis-1,2-bis-(hydroxymethyl)-3,3-difluorocyclopropane was converted into the

• the activation energies for both cis–trans-isomerization and for the transformation of vinylcyclopropanes into cyclopentenes. Both processes could occur by a C–C-bond homolysis to form a diradical. Computational studies by Gety, Hrovat, and Borden indicated that there would be a preference for

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• ) catalysis of the cyclopropanation reaction, where complex 5a-Au(III) and 6a-Au(III) gave full conversion in 1 hour and 12 hours, respectively (Table 1, entries 4 and 5). The cyclopropyl product 11 was obtained in >90% yield and high cis diastereoselectivity (up to 74% de), similar to our previous studies

• [51], which showed that JohnPhos-Au(I) and pyr-menthol-Au(III) complexes provided high amounts of the initially formed cis diastereomer in this model reaction. In contrast, some BOX-Au(III) complexes have the additional ability to rapidly transform the initially formed cis product into the isomerized

• trans product. Thus, the proper choice of the gold catalyst allows highly stereoselective formation of either cis or trans cyclopropanation products and facilitates the isolation of pure isomers. Despite the chiral nature of these ligands, no enantioselectivity was observed in the test reactions

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• photodimerization [55][56][57], photocleavage [58][59], and cis–trans photoisomerization [60][61][62][63][64][65]. While it had been well-established to access oligomer formation and gelation, a light-switchable particle size has remained a challenge until realized through the mentioned electrostatic self-assembly

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• purification in between steps. As we planned to fix substitution at C-4 to a cis-diaminocyclohexane fragment and focus our main exploration from the amide vector at C-3, we envisaged it would be more logical to exploit the cheaper and more readily-available precursor, 2-chloro-4-fluoronicotinic acid (4) with a

• morpholine amide 7. The synthesis started by selective SNAr reaction with 4 and tert-butyl ((cis)-4-aminocyclohexyl)carbamate affording the intermediate nicotinic acid 5 in 70% yield without the need for chromatography. Subsequent amide coupling using TBTU afforded 2-chloro precursor 6 in excellent yield

• ((cis)-3-aminocyclobutyl)carbamate afforded the undesired regioisomer 28 as the majority product (Scheme 5). As we were unable to exploit intermediate 26, we turned our attention to the pyridine-2-(1H)-one building block 30, easily prepared by hydrolysis of the C-2–F bond in high yield and without the

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• triene system, which is susceptible to cis–trans isomerization, have been longstanding problems in the area of inthomycins. The problems are more acute for the construction of enantioenriched β-hydroxycarbonyl units as evident from the recent reports [19][20][21]. Since the pioneering works of Henaff and

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• (−)-48, in 88% yield, as a single diastereoisomer. Then, (−)-48 was treated with trimethyl orthoformate to provide formamide (−)-49, being converted to cis-2,6-dialkenylformamide (−)-50 by treatment with the Lindlar catalyst. (−)-50 underwent a ring-closing metathesis efficiently in the presence of the

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

• ). The reaction between ethyl 2,3-butadienoate (82) and diethyl fumarate (83) in the presence of 10 mol % of triphenylphosphine afforded trans-84 in 67% yield. Under the same conditions, the use of diethyl maleate in place of diethyl fumarate (83) will give cis-84 in 46% yield (not shown). Lu and co