Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• ) [58][59][65]. Regarding the addition of diene 8c with the N-methylmaleimide (7b), a π···π interaction is discarded. Nevertheless, the endo adduct 9g was obtained as the major diastereoisomer (Table 2, entry 7). The calculated geometry at the endo TS reveals a plausible Cmethyl–H···π interaction, based

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

• , respectively (Scheme 48) [137]. Presumably, the C-centered radical formed after 5-exo-trig cyclization of the oxime radical recombines with TEMPO. The resulting adduct undergoes β-elimination of TEMPOH with the formation of final unsaturated compounds. The intermediate coupling product of the C-centered

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• with 2-bromobenzaldehydes 3 and maleimides 4 (Scheme 3) [30][37]. The cycloaddition reactions were diastereoselective (>20:1 dr for adducts 5 and >6:1 dr for adducts 6). The major diastereomers of 5 and 6 were isolated for following N-allylation and intramolecular Heck reactions. Adduct 5a generated

• ester 1 (1.2 mmol), 2-bromobenzaldehyde 3 (1 mmol) and maleimide 4 (1.1 mmol) in EtOH (3 mL) with Et3N (1.5 mmol) was heated at 110 °C for 6 h in a sealed vial. The concentrated reaction mixture was isolated by column chromatography on silica gel to afford adduct 5 in 85–90% yield. General procedure for

• on silica gel to afford adduct 6 in 75–85% yield. General procedure for the synthesis of pyrrolo[2,1-a]isoquinolines 9 or 11 To a solution of pyrrolidine adduct 5 or 6 (0.5 mmol), 3-bromopropene (7, 1.5 mmol) in MeCN (3 mL) was added K2CO3 (1 mmol), the mixture was heated at 105 °C for 4 h in a

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

• transformation, the arene is first oxidized by the excited state of the photocatalyst, generating the arene radical cation I. The latter then undergoes a nucleophilic attack of the N-heterocycle, affording the radical adduct II. TEMPO and O2 act as oxidants for the formation of the final aromatic compound via

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

• under the same conditions in the absence of F-1 produced the Diels–Alder adduct in a yield of just 10%. Conclusion In summary, by utilizing the acid–base neutralization reaction between two equivalents of NDS and one equivalent of the tetrahydrochloride salt of TAPM in water, a novel three-dimensional

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• % catalyst loading, bhomo-coupling adduct. Access to 1,2-oxy-aminoarenes by copper-catalyzed phenol–amine coupling. Copper-catalyzed aziridination through molecular spin catalysis with redox-active iminosemiquinone ligands. Nitrogen-group and carbon-group transfer in copper-catalyzed aziridination and

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• makes a hydrogen bond interaction with the NH of the 5-methoxyindole (1a) and form the adduct B. This interaction assists 1a reacting with an electrophilic ketone (2a) to form the intermediate D via C–C bond formation (C). Re-aromatization of D generates E, which then protonates to form the desired

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

• reaction generated the syn aldol adduct, having the steric configuration imposed in des-epoxy-amphidinolide N. Also, in the last step of their work, Trost et al. managed to install the C14-OH via a finely tuned Rubottom oxidation that finalized the total synthesis of des-epoxy-amphidinolide N. Strikingly

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

• at room temperature. The initial homopropargylic borane adduct, upon oxidation with NaBO3·H2O, yields the desired nonracemic tertiary alcohols 371–373 in typically high chemical yields, good diastereoselectivities, and impressive enantioselectivities. The subsequent treatment of these newly formed

• resulted in 99% of the borylated product 414, which may indicate the presence of a radical intermediate in the second, protodeboronation step. Therefore, the key intermediate is the 1,4-adduct 415, which in the presence of base and water affords the saturated product (e.g., 410, 411; Scheme 66) [129]. The

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• overnight (Scheme 1). The reaction provided the crude Ugi adduct 5a after the removal of methanol under reduced pressure. The crude residue was then exposed to a series of different cyclization reaction conditions. First, based on the previous works on the Dieckmann cyclization reaction [40][41], we

•  1, entries 9–12. DMF was superior to other solvents with the highest yield. Then the microwave irradiation temperature was varied: at 80 °C for 10 min, a large fraction of the Ugi adduct 5a was still present in the product mixture (LC–MS determination); at 120 °C, the desired compound 7a was

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• protons of the acidic imidazolium C–H and phenol O–H groups of the L4·HBF4 adduct in the presence of CuCl to generate a phenoxy copper(I) species A. As a result, all LiOt-Bu (20 mol %) is consumed in this step. Thus, the system is neutral. Transmetalation between A and (EtO)2MeSiH produces the copper

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

• . When an electron-donating group (e.g., NH, NHCO, and NMe2) was in close proximity to the alkene, the pathway of the addition changed and the chlorotrifluoromethylated adduct was formed. To explain the reaction mechanism, the authors suggested the following pathway: Upon irradiation at 530 nm using

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• trapping the radical by replacing styrene with TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl). However, GC–MS analysis indicated full conversion of TEMPO to the adduct resulting from a radical coupling between a cyanomethanide radical and TEMPO (Scheme 3) for the highly reducing [Ir(ppy)3] (−1.73 V vs SCE

Room-temperature Pd/Ag direct arylation enabled by a radical pathway

• Amy L. Mayhugh and
• Christine K. Luscombe

Beilstein J. Org. Chem. 2020, 16, 384–390, doi:10.3762/bjoc.16.36

• suppressed by the addition of TEMPO and BHT. Moreover, Ph-BHT was observed by GC–MS when BHT was added. Similar to the polymerization trials, coupling was inhibited when the standard conditions were run in the dark. Both the Ph-BHT adduct and continued poor reactivity in the dark provides growing evidence

• published results were replicated, then radical traps were introduced. In these cases, BHT completely eliminated the formation of product 12 and partially inhibited the conversion to product 13. In both cases the arene–BHT adduct was observed by GC–MS as shown in the inset of Scheme 4. While more extensive

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

• them are easily oxidized, hence the reactions are often conducted under inert conditions. Alternatively, the phosphine can be protected as a borane adduct and thereafter, the protecting group is ultimately removed to liberate the free ligand. This method has been developed by Imamoto et al. [51][52

• advantage of this fact by synthesizing a class of N-tethered phosphine imidazole ligands (Scheme 16, route A). The lithiation of the presynthesized chloromethylimidazolium iodide 82 and subsequent trapping with borane-protected di-tert-butylphosphine gave the imidazolium borane adduct 83a. The subsequent

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• copper catalysis (Scheme 15, conditions I) [39]. Mechanistically, the authors proposed the formation of a silver(I)–SeCF3 adduct, followed by a transmetallation step, yielding the active CuSeCF3 species. Good to very good yields were obtained on a broad scope, including amide-, ester-, and heterocycle

Absolute configurations of talaromycones A and B, α-diversonolic ester, and aspergillusone B from endophytic Talaromyces sp. ECN211

• Ken-ichi Nakashima,
• Junko Tomida,
• Takao Hirai,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 290–296, doi:10.3762/bjoc.16.28

• colorless solid, and HRESIMS showed a sodium adduct ion peak at m/z 341.0624 attributable to the molecular formula C16H14O7Na (calcd 341.0637) and indicative of ten indices of hydrogen deficiency. The IR spectrum exhibited absorptions due to hydroxy groups (νmax 3408 cm−1) and three carbonyl groups (νmax

• adduct ion peak at m/z 357.0572, attributable to the molecular formula C16H14O8Na (calcd 357.0586), suggesting that 2 had one more oxygen atom relative to 1. The 1H and 13C NMR data for 2 were substantially similar to those of 1, with the exception that 2 exhibited oxymethylene signals (δH 4.73 (2H, s

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• fully exploited so far, some contributions on the diversity-oriented synthesis of spirocyclic compounds have appeared in the literature recently, also employing multicomponent approaches to give the spirocyclic adduct after a cyclization step [34][35][36]. We recently focused our interest to the

• basic nitrogen atoms [28]. The variation of the alkyne component proved to give the KA2 coupling adduct when aromatic terminal alkynes were used, as shown in Table 1, entries 1 and 2 for those containing phenyl and thienyl moieties, resulting in 82% and 74% yield for the KA2 step. Subsequent acylation

• spirocyclopentenone derivative, although in slightly lower yield as compared for the homologous ketone (Table 1, entry 5). No conversion to the KA2 adduct was achieved by using unsaturated or aromatic ketones (Table 1, entries 7 and 8, respectively), confirming an important role of the electronic content of the

[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

• molecule additionally activated the γ-carbon atom for a sulfur attack. Regarding the correctness of the proposed mechanism, two issues associated with the reactivity of 17 and 19, respectively, in the presence of AlCl3 must be discussed. The first is the formation of the adduct with tert-butyl methyl

• ketone, and the second is the formation of the adduct with acetone. For 17, the formation of β,γ-alkenylphosphine sulfide was not possible, whereas the transformation of 19 afforded mainly the α,β-unsaturated compound 35. DFT analysis of the C–O bond cleavage in the adducts analogous to I revealed two

• sulfide, which then underwent coordination of the second AlCl3 molecule, with an overall slight stabilization (+6.0/−8.5 kcal/mol). The adduct analogous to IV underwent methyl group migration to the β-carbon atom, along with the formation of a covalent Al–C bond. The last step required a remarkable

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• benzyl protected serine at the Dha site. Following hydrogenolytic deprotection, in situ produced serine EDC adduct was subjected to copper(I) chloride-mediated elimination to give the dehydroalanine derivatives 34a and 34b in good yields. Deprotection of the ester protecting group also proceeded in good

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• -resolution positive electrospray ionisation mass spectrometry (HRESI(+)MS) analysis of nanangenine A (1) revealed an adduct ion ([M + Na]+ m/z 305.1363) indicative of a molecular formula C15H22O5 requiring five double bond equivalents (DBE). No distinguishing absorption maxima were observed in the UV–vis

• (Table S2 and Figure S3 in Supporting Information File 1). HRESI(+)MS analysis of nanangenine B (2) revealed an adduct ion ([M + Na]+ m/z 403.2096) indicative of a molecular formula C21H32O6. The NMR data for 2 (Table S4 in Supporting Information File 1) were very similar to those for 1, with the only

• S4 in Supporting Information File 1). HRESI(+)MS analysis of isonanangenine B (3) revealed an adduct ion ([M + Na]+ m/z 403.2094) indicative of a molecular formula C21H32O6, which is isomeric with 2. Comparison of the NMR data for 3 (Table S5 in Supporting Information File 1) with those for 2

Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

• Vânia F. Pais,
• Tristan Neumann,
• Ignacio Vayá,
• M. Consuelo Jiménez,
• Abel Ros and
• Uwe Pischel

Beilstein J. Org. Chem. 2019, 15, 2612–2622, doi:10.3762/bjoc.15.254

• (17), 426 nm (18), 425 nm (19). This points to the interpretation that the SW emission has its origin in a Lewis adduct between the boron center as acceptor and the solvent as donor. The maxima of the rather broad LW bands of the dyes are observed between 510 and 590 nm in acetonitrile, corresponding

• LW band is substituted by a strong blue-shifted emission. This leads to a clear ratiometric behavior and a large dynamic response. The blue-shifted emission for the fluoroboronate Lewis adduct is in accordance with the observations made for donor solvents such as tetrahydrofuran (see above). As for

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• cysteine sulfhydryl side chain to electrophilic Cβ of an O-acetylated Morita–Baylis–Hillman (MBH) adduct residue (Scheme 1). Despite reports describing the use of amino acid residues with nucleophilic side chains to prompt the macrocyclization of peptides and their mimetics, to the best of our knowledge

• new C–S bond. The configuration of the double bond could be assigned as Z for all compounds due to the 1H,1H-NOESY correlations between the C3 hydrogen and the NH hydrogen of the amino acid residue attached to the adduct residue. The IR spectra of analogues 9 were quite similar (Supporting Information

• , some observations can be made: (1) 9e is the only one among all the analogues derived from the acetaldehyde adduct that, regardless of the configuration of the stereogenic centres, has the same amino acid residue sequence found in solonamides; (2) despite the close similarity on the amino acid residue

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

• (III) chloride in methanol in 88% yield (Scheme 1). The synthesis of allylic alcohol 11, a regioisomer of 6, started again from (1R)-α-pinene (1, Scheme 2). Hydroboration of (1R)-α-pinene with borane–dimethyl sulfide adduct (BMS) and crystallization of the product diisopinocampheylborane (dIpc2BH, 84

• % yield. The allylic diphenylphosphine oxide 21 was subjected to the hydroboration–oxidation reaction introducing stereoselectively the hydroxy group. Hydroboration was carried out with an excess of borane–dimethyl sulfide adduct followed by the oxidation step. The standard C–B bond oxidation protocol

• borane–dimethyl sulfide adduct in THF at 50 ºC. Oxidation of the alkylborane with mCPBA gave the desired alcohol 27 in 51% overall yield. Finally, diastereomeric endocyclic allylic alcohols 16 and 18 were treated with chlorodiphenylphosphine in the presence of DMAP to produce diphenylphosphinites 28 and

Reversible switching of arylazopyrazole within a metal–organic cage

• Anton I. Hanopolskyi,
• Soumen De,
• Michał J. Białek,
• Yael Diskin-Posner,
• Liat Avram,
• Moran Feller and
• Rafal Klajn

Beilstein J. Org. Chem. 2019, 15, 2398–2407, doi:10.3762/bjoc.15.232

• affected by their confinement to the surfaces of inorganic nanoparticles. Among other examples, the isomerization kinetics of azobenzene could be tuned by a factor of >5000 by the molecules with which it was co-adsorbed on gold nanoparticles [23], and donor–acceptor Stenhouse adduct (DASA) switches were