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

• inter- and intramolecular versions. Furthermore, the use of vinyl fluorides as olefinic counterparts had been completely overlooked. In this review, we collect the advances both on the stoichiometric and catalytic intermolecular and intramolecular fluoro-Pauson–Khand reaction, with special attention to

• groups at the vinylic position, very few examples have been described to date. In this context, our group recently explored the reactivity of 1,n-enynes bearing a vinyl fluoride moiety as the olefin counterpart in the intramolecular PKR [59] (Scheme 18). The study of the behavior of this kind of

• recovered, in agreement with previous precedents describing that trisubstituted alkenes are very unreactive substrates in this kind of process (Scheme 28) [65]. The influence of the introduction a vinyl fluoride moiety on the PKR was also investigated (Scheme 29). The resulting cyclopentenones 57 were

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• of such cases where an aryl radical, formed via the photocatalyzed reduction of diazonium salt 2.1+, added to methyl propiolate. Ensuing cyclization of the resulting vinyl radical 2.2· finally yielded the desired phenanthrene 2.3 [41]. A different approach involves the intramolecular cyclization of α

• -bromochalcones (Scheme 3). Thus, compounds 3.1a–d underwent a one-electron reduction by the excited photocatalyst fac-Ir(ppy)3. Upon bromide anion loss, the α-keto vinyl radicals 3.2·a–d were then formed, which smoothly added onto the vicinal aromatic ring in an intramolecular fashion, affording phenanthrene

• -obtained α-oxyalkyl radical intermediates were then trapped by biphenyl (or vinyl) isocyanides to afford functionalized phenanthridines, such as 9.3a (or quinolines) (Scheme 9, path a) [70]. A photogenerated nitrogen-based radical was likewise used to cleave the C–H bond α-to-nitrogen in amides to form the

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• Michael acceptor, as such is currently popular in the development of covalent inhibitors [43]. The reaction was carried out in the presence of 12 equiv BTMS at 35 °C. The disappearance of the signals originating from the vinyl protons (multiplets at δ 5.56–5.66 and 5.95–6.10 ppm) and the appearance of the

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• , cyclopentanone, and three carbon ring-expanded 1,3-diones from vinyl spiro epoxides [14]. The reaction is initiated by the addition of a thiyl radical to the vinyl epoxide 24, followed by the epoxide fragmentation to the alkoxy radical 25. Then, the β-cleavage to form the carbon-centered radical 26, the final

• expansion of vinyl spiro epoxides. Disulfide-catalyzed aerobic oxidation of diarylacetylene. Disulfide-catalyzed aerobic photooxidative cleavage of olefins. Disulfide-catalyzed aerobic oxidation of 1,3-dicarbonyl compounds. Proposed mechanism of the disulfide-catalyzed aerobic oxidation of 1,3-dicarbonyl

Recent synthesis of thietanes

• Jiaxi Xu

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

• retention and inversion products [63] (Scheme 38). However, some olefins, such as cyclohexene, oct-1-ene, vinyl ether, vinyl sulfide, etc., produced 1,4-dithiane derivatives as products through the reaction of two molecules of thiobenzophenone (184a) and one molecule of the olefin under irradiation with 589

• 264 formed preferably, in the reaction of 256 with ethyl vinyl ether (215e) and propen-2-ylbenzene (186a). Notably, the photoreaction of 2,4-dithiobarbiturate 257 and 2,3-dimethylbut-2-ene (215a) produced exclusively the 4-thietane derivative 265 in 91% yield. 2,4,6-Trithiobarbiturate 258 reacted with

• stereocontrol were obtained when 316 was reacted with electron-rich olefins, as for example, vinyl ethers [87] (Scheme 58). In 2003, Sakamoto and co-coworkers investigated the intermolecular diastereoselective photo [2 + 2] cycloaddition of axially chiral monothiosuccinimides 319 which could enantiomerize into

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

• tetrahydroindole skeleton) [32]. Any attempt to isolate or detect 17 during the trials turned out to be unsuccessful [35]. It is noteworthy that there have been almost no reports to date on the uncommon highly diastereoselective Diels–Alder reactions of analogous 2-vinyl or 3-vinylpyrroles [32], nor on the

• the solvent at 100 °C afforded pyrrolo[2,1-a]isoindoles 18a–c in good yields. This annulation process was regioselective, showing a preference of the cross-coupling reaction with the C-5 pyrrolic position and not with the vinyl moiety, which would give the dihydropyrrolo[1,2-b]isoquinoline 19. A

• ,b with maleimides 7b,c proved to be highly endo diastereoselective. This selectivity turned out to be significant in the case of vinyl benzopyrrolizine 18a as well. The consecutive Pd(0) cross-coupling reaction of some of the Diels–Alder adducts allowed for the synthesis of a numerous series of

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

• of free radicals (Scheme 9). It remains unchanged [45] when dissolved in styrene (2 hours, 25 °C) or vinyl acetate (20 minutes, 60 °C; conversion of the oxime radical was less than 10% after 3 days at 25 °C). The inertness of the di-tert-butyliminoxyl radical with respect to the mentioned substrates

• involving an isonitrile group is the reaction of β,γ-unsaturated oximes 119 with vinyl isocyanides 120 to form substituted isoquinolines 121 (Scheme 39) [129]. Both α,α-disubstituted aromatic oximes (products 121a,b,e–h) and unsubstituted (R2 = R3 = H, products 121c,d) undergo the reaction successfully. The

• authors noted the effect of substituents in the phenyl fragment attached to the oxime group (R1): high yields were obtained with para- and meta-substituted substrates; however, when ortho-substituents were present, the product 121 was not observed. Two aryl groups at the vinyl fragment of the isocyanide

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

• reaction (Scheme 23) [100]. The alkynes 23.1 could be successfully converted to the vinyl sulfones 23.3 in the presence of the aryl sulfones 23.2 using eosin Y (OD13) as a photocatalyst. A tentative mechanism was proposed by the authors: under visible-light irradiation, the arylsulfinic acid could be

• desired vinyl sulfones. C–X radical anions and derived neutral radicals Amidst charged radical species, ketyl radicals play a central role in organic synthesis (Figure 3). As intermediates, they are more stable because the charge is mainly localized on the oxygen atom. They are postulated to be the

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

• , including the ring opening of epoxides by water and alcohols. A Diels–Alder reaction between cyclopentadiene and methyl vinyl ketone was also catalyzed by F-1 in heptane. Depending on the polarity of the solvent mixture, the CAHOF F-1 could function as a purely heterogeneous catalyst or partly dissociate

• 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

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• the 1H NMR spectra from the disappearance from the aromatic region of the signal due to the vinyl proton of the oxazolone exocyclic C=C bond and the appearance of a new singlet in the 4.8–5.7 ppm region. Further evidence can be found in the 13C NMR spectra, where the two peaks due to the exocyclic C(H

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• -alkynyltrifluoroacetanilides. In all these procedures, the activation of the triple bond was achieved by means of a σ-organyl palladium complex, in turn generated in situ by oxidative addition of a Pd(0) species to suitable organic electrophiles (aryl and vinyl halides or triflates [35][36], alkyl halides [37], alkynyl

• -assisted cyclization and reductive elimination from the resulting σ-indolylpalladium complex C (Scheme 5). The reaction led to the stereoselective formation of indole derivatives 6ba–fc (aryl, heteroaryl and vinyl groups were allowed in substrates 5) in good to high yield. The stereochemistry of compounds

• process has been significantly extended to include σ-vinyl Pd(II) intermediates B obtained through oxidative addition/insertion of substrates 2 with Pd(0). This reaction efficiently led to challenging indoloquinolinones 6 through a sequential double cyclization. It is worth noting that, in both cases, the

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• and vinyl iodides by a copper-mediated transformation using TMSCF2H as the fluorinated source [39]. In this work, CuCF2H was suggested as the active species to promote the expected transformation. They highlighted that the formation of a cuprate species: Cu(CF2H)2−, favoured by the presence of an

• the functionalization of different classes of compounds (benzyl and vinyl bromides, 4-biphenylboronic acid, phenylacetylene for instance). From these pioneering reports of perfluoroalkylation (trifluoromethylation, pentafluoroethylation and heptafluoropropylation), several groups studied the synthesis

• (hetero)aryl bromides (11 examples, up to 98% 19F NMR yield) via the in situ generation of the suitable CuCF2CF3 from CuCl, KOt-Bu or NaOt-Bu and ethyl pentafluoropropionate [73]. Note that the methodology was also applied to the functionalization of a vinylboronic acid and a vinyl bromide (Scheme 18

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• the protected ᴅ,ʟ-N-Boc-2-bromophenylalanine (89) using a Stille coupling reaction to give the o-vinyl derivative 90 as key intermediate. A hydroboration reaction of compound 90 afforded the primary alcohol 91, which was directly fluorinated and deprotected to give the free amino acids 93 (ᴅ and ʟ

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

• catalyst is essential for achieving a high yield as well as a high regio- and enantioselectivity (up to 99% ee). Although organoaluminium, organozinc, and Grignard reagents were all successfully applied in the ACA of 2,3-dehydro-4-piperidones, an introduction of the vinyl group was not successful until

• 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

Synthesis and properties of tetrathiafulvalenes bearing 6-aryl-1,4-dithiafulvenes

• Aya Yoshimura,
• Hitoshi Kimura,
• Kohei Kagawa,
• Mayuka Yoshioka,
• Toshiki Itou,
• Dhananjayan Vasu,
• Takashi Shirahata,
• Hideki Yorimitsu and
• Yohji Misaki

Beilstein J. Org. Chem. 2020, 16, 974–981, doi:10.3762/bjoc.16.86

• -dithiole rings, which are of interest as novel multistage redox systems as well as donor components for organic conductors [1][31][32][33][34][35][36][37][38][39][40][41]. The palladium-catalyzed C–H arylation might offer access to new cross-conjugated molecules bearing vinyl-extended TTF moieties (EBDTs

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• -Trimethylspiro[indoline-2,3'-naphtho[2,1-b][1,4]oxazine]-5'-yl)vinyl)quinolizinium tetrafluoroborate (3a) [60][62][64][65]: To a solution of 2-methylquinolizinium tetrafluoroborate (2a, 116 mg, 500 µmol) and the 5’-formyl-substituted spirooxazine 1b (214 mg, 600 µmol) in MeCN (15 mL) was added piperidine (42.6

• . (E)-8-(2-(1,3,3-Trimethylspiro[indoline-2,3'-naphtho[2,1-b][1,4]oxazine]-5'-yl)vinyl)coralyne tetrafluoroborate (3b) [60][62][64][65]: To a suspension of coralyne tetrafluoroborate (2b, 90.2 mg, 200 µmol) and the 5’-formyl-substituted spirooxazine 1b (143 mg, 400 µmol) in MeCN (6 mL) was added

• /b = 20 µM and cCu(II) = 60 µM. (E)-2-(2-(2-(1,3,3-Trimethyl-3H-indol-1-ium-2-yl)naphtho[1,2-d]oxazol-4-yl)vinyl)quinolizinium (4a): 1H NMR (600 MHz, CD3CN) δ 2.11 (s, 6H, 2 × 3’-Me), 4.81 (s, 3H, N+Me), 7.80–7.88 (m, 3H, 6’-H, 5’-H, 7’’-H), 7.91–7.98 (m, 4H, 4’-H, 7-H, CH, 8’’-H), 8.04 (d, 3J = 8 Hz

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• excellent yields. However, benzyl and vinyl bromides did not prove efficient for this coupling reaction. Common cyclic and acyclic ethers, symmetric or nonsymmetric, such as oxetane, tetrahydropyran, dioxane, 2-methyltetrahydrofuran, and 2-methoxy-2-methylpropane, were found compatible, affording the

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

• coordinated to the metallacarbene and cleaved (Scheme 3 (a)) and the formed alkylidene species is inserted into the alkyne unit through a metallacyclobutene intermediate. This metallacyclobutene, through the rearrangement to a vinyl metal-alkylidene (Scheme 3 (b)) and subsequent metathesis with the alkene

• synthesized starting from ʟ-methionine. The subsequent enyne ring-closing metathesis in the presence of the Grubbs first-generation catalyst (5 mol %) afforded a pyrrolidine derivative in 76% yield (Scheme 12). This pyrrolidine was converted into a pyrrolo-1,4-benzodiazepinone bearing a vinyl side group

• , which underwent a cross-metathesis with ethyl acrylate in the presence of the Hoveyda–Grubbs second-generation-type catalyst (10 mol %) leading to the corresponding vinyl ester 8 in 63% yield, as a convenient precursor to (+)-anthramycin. The latter was obtained via an isomerization of the double bond

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

• 219. Based on the type of ligands used (e.g., Me-DuPhos; L24 vs. Cy3P), either vinyl (220–223) or allylic (224–228) silanes could be obtained, respectively, in good yields. Different types of substrates were studied to give maximum selectivity for the desired product (Scheme 38). Also, for cases

• 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

• developed by Suginome [125], or B2pin2, along with various N-hydroxylamine derivatives (400) under ligand-influenced Cu catalysis, high regioselectivities were typically obtained [126]. A year later, Popp et al. reported a Cu-catalyzed regiospecific boracarboxylation of vinyl arenes using 1 atm CO2 and

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

• to generate 13a and 13b as a mixture of regioisomers in a ratio of 4:1. There was no requirement to separate these isomers at this stage. Subsequent addition of potassium tert-butoxide into a mixture of 13a and 13b in dichloromethane (DCM) resulted in an efficient elimination to generate vinyl

• fluoride 14 as a major product. Vinyl fluoride 14 was purified by column chromatography in a 42% yield over the two steps. Finally, difluorocarbenene (:CF2) addition using the TMSCF3/NaI protocol was used to generate the target product 9 in 46% yield. The preparation of cyclopropyl ether 10 was

• accomplished as illustrated in Scheme 3. Reduction of cyclohexanone 15 with NaBH4 gave cyclohexanol 16 in a ratio of 2:1. The major trans product 16a was purified as a single entity by column chromatography and was isolated in 45% yield. Vinyl ether 17 could be efficiently prepared using the methodology

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• obtained through a seven-step sequence starting from ᴅ-ribonic acid-1,4-lactone. The (Z)-vinyl bromide 4 is accessible in four steps from 4-hydroxybenzaldehyde. The pivotal cross coupling between both fragments was achieved after extensive experimentation with copper(I) iodide, K2CO3 and N,N

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• , and difluoromethyl vinyl sulfonium salts as the fluorinating partner en route to various CF2-substituted aziridines [27][28][29][30][31], and a general protocol to chiral CF2-aziridines remains an unsolved challenge. Thus, herein we report a diastereo- and enantioselective aza-Darzens reaction between

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• has allowed to perform a wide range of previously unknown synthetic transformations [19][20][21][22][23][24][25][26][27][28][29]. In these reactions, aryl(vinyl)Cu(III) species [30][31] have been proposed as key intermediates to undergo reactions with a variety of nucleophiles. Fañanás-Mastral and

• triflic acid via decomposition of ethyl triflate. As a limitation, substrates bearing a vinyl substituent or an enolizable ester group did not give any conversion. This methodology is also applicable to other dialkyl phosphonates as illustrated by the synthesis of enol phosphonates 3j, 3k and 3l

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• a regio- and stereoselective manner affording 1,3-thiaselenol-2-ylmethyl vinyl selenides in high yields predominantly with Z-configuration. Not a single representative of the 1,3-thiaselenol-2-ylmethyl selenide scaffold has been previously described in the literature. Keywords: 2-(bromomethyl)-1,3

• of bis(trimethylsilyl)selenide [23]. The methodology based on bis(trimethylsilyl)selenide was also successfully applied to the synthesis of functionalized asymmetric alkyl- and vinyl selenides, including cyclic disubstituted 1,3-thiaselenolane and trisubstituted thiaselenane [26][27]. Vinyl selenides

• [38][39], dithiols [38], and mercapto benzazoles [40]. These are the first examples of a nucleophilic attack at the selenium atom of the seleniranium cation 2 with the generation of a new Se–S bond, yielding new families of linear unsaturated (Z)-2-[(organylsulfanyl)selanyl]ethenyl vinyl sulfides