Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• ]. A wide range of pharmaceuticals, agrochemicals, and other biologically active compounds are prepared using different types of (3 + n) cycloadditions, mainly with alkenes and alkynes [3][4][5][6][7]. For example, N,N'-cyclic azomethine imines are precursors of biologically active bicyclic

• the hexahydropyrazolo[1,2-a]pyrazole ring, respectively, apparently through zwitterionic intermediates [28][29]. At the same time, the cycloaddition of azomethine imine to 1,3-diphenylprop-2-en-1-ones (chalcones) in IL proceeds stereo- and regioselectively giving two diastereomeric bicyclic anti

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• (rac)-11b was unequivocally established by single-crystal X-ray diffraction (Figure 1). Then, the preparation of another model compound, the trans-annelated bicyclic carbamide derivative (rac)-13, was attempted. This compound was also unknown in the literature. In the reaction of commercially available

• mind, further plans concerning compound (rac)-13 were abandoned. We continued our studies with strained, rigid bicyclic systems. First, the N-Boc-protected Vince lactam (rac)-14 was subjected to halofluorination reactions. Despite the asymmetric nature of the olefin, the compounds (rac)-15a and (rac

• both NOESY measurements and single-crystal X-ray diffraction (Figure 2 and Figure 3). The next rigid bicyclic system studied was the methyl diendo norbornene dicarboxylate 16. The treatment of 16 with NBS/Deoxo-Fluor® yielded the bromolactone (rac)-17a [37]. The reaction, when repeated only with NBS

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• to allenes 80 to give complex bicyclic products 81 in moderate yields and good enantioselectivities (20 examples, up to 92:8 er) (Scheme 9b) [47]. The Bach group recently developed an enantioselective synthesis of cyclobutane 82 from enal 83 and diene 84 (Scheme 11a) [48]. Most of the examples

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• primarily engaged in synthesizing various types of such multichromophoric systems to compare their photochemistry in detail [9][10][11][12][13][14][15]. Since in acyclic enones like C, E/Z-photoisomerization becomes one of the major energy dissipation pathways, we selected rigid bicyclic multichromophoric

• efficiently via a triplet-mediated pathway without use of any external sensitizer. Similar to bicyclic systems, some of the tricyclic system like 1h yielded 1,2-AS product 2h under similar reaction conditions [16]. Initially we envisaged two mechanistic pathways: the oxa-di-π-methane (ODPM) path

• photoreactions of bridged bicyclic systems like 3a–g were carried out [9][10][11][12][13]. These molecules contain a δ-keto-α,β-enone system juxtaposed with a (cis)-dibenzoylalkene moiety. Interestingly, photoreactions of 3a–f were found to follow regioselective photoindiuced 1,5-phenyl migration from the more

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• conditions and no fluorinated product was observed, contrary to Chen’s previous report [201]. The monofluorination of different classes of ketones, including 3° alkyl compounds or benzylic cyclohexanones, bicyclic ketones and steroidal ketones was achieved in moderate to excellent (43–85%) yield (48–55

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• thiol from exo-face of the bicyclic skeleton. Subsequent simultaneous phosphorylation and oxidation of ethyl 2-thio-ᴅ-tagatofuranoside 13 under identical conditions as used for the fructofuranose pathway provided 1-O-dibenzyloxyphosphoryl-ᴅ-tagatofuranosyl sulfone 14 (Scheme 3). Removal of the pivaloyl

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• discussed in detail. The focus of this review is to highlight the efforts made in the field of the Pauson–Khand reaction with fluorinated compounds for the preparation of bicyclic derivatives. Review The Pauson–Khand reaction The Pauson–Khand reaction (PKR) formally consists of a [2 + 2 + 1]-cycloaddition

• equiv of NMO, yielding bicyclic derivatives 19 in moderate yields and high diastereoselectivity (de > 95%). The observed diastereoselectivity was rationalized considering two transition states of the PKR, and assuming the CF3 group occupies an axial position due to the steric and electrostatic

• bicyclic compound since the double and triple bonds are too distant. In a following paper by Billard and co-workers, the PKR of oxygen-containing 1,7-enynes was assayed, affording trifluoromethylated oxygenated bicyclic enones (Scheme 9) [48]. Under classical stoichiometric conditions (reaction with Co2(CO

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• a constant HFC aN = 30 G and 32 G, corresponding to iminoxyl radicals 93. At higher temperature (+10 °C), only one signal was observed with aN = 19.75 G. This HFS value is characteristic of bicyclic nitroxyl radicals [123]. The authors suggested that the formed iminoxyl radical underwent cyclization

• with the formation of alkyl radical 94. The latter attacked the nitrone moiety to form the bicyclic nitroxyl radical 95. When oxime 96 was oxidized with lead(IV) acetate, products 98 and 99 were observed. This result can be explained by the intramolecular attack of iminoxyl radical 97 on the phenyl π

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• performs an SET oxidation of an cyclopropylaniline 36.1, leading to an N-centred radical cation after ring opening. The latter undergoes a [3 + 2] annulation with cyclopropenes 36.2, affording a bicyclic product 36.3. The key to the broad substrate tolerance relied on using 4DPAIPN (OD7), which is a mild

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• is to employ both donor and acceptor moieties in a single molecular structure [1][2][3][4]. Quinazoline is a planar aromatic heterocyclic compound with the fused bicyclic structure consisting of benzene and pyrimidine rings. Quinazoline derivatives were investigated and used in medicinal applications

The charge-assisted hydrogen-bonded organic framework (CAHOF) self-assembled from the conjugated acid of tetrakis(4-aminophenyl)methane and 2,6-naphthalenedisulfonate as a new class of recyclable Brønsted acid catalysts

• Svetlana A. Kuznetsova,
• Alexander S. Gak,
• Yulia V. Nelyubina,
• Vladimir A. Larionov,
• Han Li,
• Michael North,
• Vladimir P. Zhereb,
• Alexander F. Smol'yakov,
• Artem O. Dmitrienko,
• Michael G. Medvedev,
• Igor S. Gerasimov,
• Ashot S. Saghyan and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2020, 16, 1124–1134, doi:10.3762/bjoc.16.99

• partitioning of the epoxide into the aqueous phase was necessary for reaction to occur. Cyclohexene oxide (5) is, however, a good substrate under the same reaction conditions (Table 2, entry 5), possibly due to the greater reactivity of its fused bicyclic ring system. The Diels–Alder reaction of methyl vinyl

A simple and easy to perform synthetic route to functionalized thienyl bicyclo[3.2.1]octadienes

• Dragana Vuk,
• Irena Škorić,
• Valentina Milašinović,
• Krešimir Molčanov and
• Željko Marinić

Beilstein J. Org. Chem. 2020, 16, 1092–1099, doi:10.3762/bjoc.16.96

• of two aromatic units (Scheme 1). The idea herein was to prepare thienyl analogues of the annulated furyl derivatives, as substrates suitable for biological testing and/or new precursors for further functionalization. Results and Discussion As starting precursors two bicyclic thiophene derivatives 1

• -isomers 3–6 as representative examples. The detailed analysis of all new compounds' NMR spectra can be found in Supporting Information File 1. The 1H NMR spectra of the presented examples confirmed the conservation of the bicyclic core. Six proton pattern, characteristic for these bicyclic systems, were

• bicyclic skeleton preserved. The UV spectrum of the aldol product 12, in comparison to the starting aldehyde 1, showed the expected red shift, under the prolonged conjugation in product 12 (Figure 10). Contrary to the results obtained on the styryl analogs 3–7, the preliminary irradiation experiments of

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• the synthesis of the corresponding products with good yield and enantiomeric purity (up to 83% yield and 97% ee). Furthermore, a large variety of vinylalanes was investigated, and the product 2l was further derivatised into a chiral bicyclic structure (5, Scheme 2A). In addition, simple vinyl

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• the corresponding bicyclic dienic scaffolds. The subsequent hydroboration and aminohydroxylation carried out on these bicyclic dienes provided the AB subunit as a key intermediate component of manzamines A (16a) and E (16b, Scheme 19). Eventually, several highly elaborated transformations of the AB

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• the details of the mechanism for the hydrofunctionalization of internal alkenes and vinyl arenes (Scheme 55) [100]. Unlike acyclic alkenes, Tortosa et al. utilized cyclobutenes as well as bicyclic cyclobutenes as educts using (R)-DM-Segphos for Cu-catalyzed enantioselective borylation, affording

• on the interest in Cu-catalyzed aminoboration reactions of a variety of alkenes, such as bicyclic alkenes [124], Miura et al. subsequently described the preparation of β-borylalkylamines 401–404 from unactivated terminal alkenes 307 (Scheme 64). Using a mixed diborane reagent, such as pinB–Bdan

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• CF2-containing cyclopropanes 11a and 11b became targets to assess the impact of a configurationally rigid bicyclic motif. It is relatively obvious that for each of these isomers the CF2 dipole in each cyclopropane is orientated either along the molecular axis (for 11a) or perpendicular to the

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• yields often >80%. Keywords: amidation; DBU; folate; pterin; Introduction Pteridines are a class of fused bicyclic heterocycles with significant biological relevance. The 2-amino-4-pteridinone core, simply referred to as “pterin”, is present in various biological cofactors like folates, biopterin, and

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• the best copper-based photocatalyst, Collins and co-workers reported the synthesis of a bicyclic lactone by a PCET reaction manifold (Scheme 32) [39]. Using their methodology, the authors discovered the [Cu(I)(quinitri)(xantphos)]BF4 catalyst as the best one, which afford the cis-lactone in 79

• ester derivatives. δ-Functionalization of alcohols using [Cu(I)(dmp)(xantphos)]BF4. Photocatalytic synthesis of [5]helicene and phenanthrene. Oxidative carbazole synthesis using in situ-formed [Cu(I)(dmp)(xantphos)]BF4. Copper-photocatalyzed functionalization of N-aryl tetrahydroisoquinolines. Bicyclic

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• with aminosilanes which produces trimethylchlorosilane as a byproduct which can be distilled off easily [102]. Bicyclic guanidine frameworks present an opportunity to form inflexible ligands that are inclined to exhibit a κ2-P,N-bonding mode in metal complexes. Dyer et al. [103] prepared cycloguanidine

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• . The nature of this difference is currently a subject of further research in our laboratory. Nevertheless, the above results opened a new pathway for the synthesis of bicyclic organophosphorus compounds possessing a chirality center at phosphorus. Moreover, the formation of the bicyclic compounds

• stereoselectivity. It was found that the P-stereogenic β-/γ-mercaptoalkylphosphine oxides underwent intramolecular cyclization to the corresponding bicyclic phosphine oxides with high stereoselectivity and high yield under mild reaction conditions. 1H NMR spectra of compounds 12 and 29. 13C NMR spectra of compounds

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• cationic species. For instance, remodeling the hydrophobic pocket of the active site by single-point mutation, epi-isozizaene (33) synthase was engineered to produce various linear, monocyclic, bicyclic, and tricyclic terpene skeletons (Figure 9b) [119][120][121]. Another prominent example is cyclooctat-9

• , simply by rationally mutating the active-site residues. The majority of bacterial type II diterpene TCs produce bicyclic labdane, halimadane, or clerodane skeletons with different stereochemistry, levels of unsaturation, and hydroxylation patterns [124], which undergo further conversion with their

• (Figure 10b) [131]. Similarly, by mutating two residues of P450BM3 that control the shape of the substrate binding cavity, the enzyme was engineered to accept different linear, monocyclic, and bicyclic terpenes [132]. The alteration of the native sequences uses either method or the combination of the two

Synthesis of aryl-substituted thieno[3,2-b]thiophene derivatives and their use for N,S-heterotetracene construction

• Nadezhda S. Demina,
• Nikita A. Kazin,
• Nikolay A. Rasputin,
• Roman A. Irgashev and
• Gennady L. Rusinov

Beilstein J. Org. Chem. 2019, 15, 2678–2683, doi:10.3762/bjoc.15.261

• light-harvesting dyes for dye-sensitized solar cells [1], electron-donating materials for bulk heterojunction solar cells [2][3][4], and p-type semiconductors for organic field-effect transistors [5][6][7]. Within the same context of organic semiconductor development, the bicyclic TT subunit has been

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• in hydride abstraction with the formation of carbocation 9 and subsequent cyclization to the bicyclic alkoxyamine 10. The resulting isoxazolidine ring is then opened with m-CPBA in the usual way, retaining the configuration of the asymmetric center at 3aC-OH [13] (Scheme 4). The steric strain in

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• rearrangement reaction may be the rigid bicyclic structure of the substrate and steric hindrance on one side of the molecule caused by the gem-dimethyl bridge. Conclusion Regioisomeric exocyclic allylic alcohols were synthesized from natural α-pinene. (1R,2R,4S,5R)-3-Methyleneneoisoverbanol and (1R,2R,3R,5R)-4

• the less hindered side of the molecule to produce γ-hydroxyphosphine oxide derivatives. It was also shown that phosphine oxide can be reduced to phosphine without affecting the bicyclic pinane structure. The synthesis of diastereomeric endocyclic allylic alcohols from (−)-β-pinene was also carried out

• . Unfortunately, due to the probably too rigid bicyclic structure of the diphenylphosphinites, they did not undergo the sigmatropic rearrangement to the corresponding phosphine oxides. Further research and application of the obtained ligands are in progress. Experimental Diphenyl(((1R,2R,5S)-δ-pinen-3-yl)methyl