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 Oestreich group in 2016 [27]. The reaction could be performed using CuCN as catalyst in the absence of a ligand. A wide variety of triflates 9, including some containing a remote tosylate, bromide, alkene, or alkyne functionality, afforded the desired alkylsilanes 10–16 in fair to good yields

• also supports a radical mechanism, is depicted in Scheme 7. Here, an intermediate radical could easily be intercepted by a tethered alkene in 30 leading to a 5-exo-trig cyclization and hence, the formation of a 5-membered ring as found in products 31–33. The formation of, e.g., compound 34, suggested

• that a specific geometry of the tethered alkene is required, as no 6-membered ring formation was observed. Interestingly, Cárdenas’ precursor 35 [30] led, after a cascade of reactions, to the formation of compound 36. Computational as well as experimental studies suggested that the ligand and

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• role of the electronic effects of the nitrogen atoms on this cyclic substrate, and then we revised our synthetic strategy by a) tethering an alkene functional group on the aromatic ring and b) then conducting the oxidation of the benzylic group to afford the aldehyde product. Towards this end, we

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• alkene derivatives. Because an alkyne undergoes addition reaction at a C–C triple bond or cross-coupling at a terminal C–H bond. Combining those reaction patterns could realize a new reaction methodology to synthesize complex molecules including C–C multiple bonds. In this report, we found that the

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

• subsequently adds to the alkene. The resulting C-centered radical is oxidized by the Cu(II) complex, regenerating the Cu(I) catalyst, and the formed carbocation is trapped by the halide. Worth to mention is that very recently, Reiser and Engl demonstrated the possible use of [Cu(dmp)2Cl]Cl as an efficient

• . 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

• to the alkene, followed by the addition of SO2Cl to produce the desired product. However, when the reaction rate is slower, the SO2Cl anion decomposes to neutral SO2 and a chloride anion due to the weak nature of the Cu–SO2Cl bond. The SO2 extrusion explains the formation of the

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

• cycle. This type of mechanism has been previously proposed for aryl and alkene alkylations [27][28], but not for direct arylation systems. A possible mechanism is outlined in Scheme 3, informed by the previous reports [27][28][29][30]. The aryl iodide 4 undergoes SET with an excited palladium(0) species

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• and co-workers, who developed a one-pot, three-component reaction to produce protected homoallylic amines 4 (Scheme 1) [19]. It was reasoned that adaptation of the Veenstra protocol would allow us to introduce a second alkene unit during the same process, thus generating a ring-closing metathesis

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• comparison with literature data [69], and the new compounds 3b and 3d were fully characterized by NMR spectroscopy (1H, 13C, COSY, HSQC, and HMBC), elemental analyses, and mass spectrometry. In all cases, E-configuration of the alkene double bonds in 3a–d was indicated by characteristic coupling constants of

• the alkene protons (3JH–H = 16 Hz) [70]. Absorption and emission properties The photophysical properties of the styrylquinolizinium derivatives 3a and 3c have already been reported [69], while the ones of 3b and 3d were determined in this work (Table 1 and Figure 1). In acetonitrile, the derivatives

• irradiation at λ = 450 nm or λ = 360 nm in acetonitrile, as indicated by the upfield shift of the signals of the alkene double bonds and the characteristic coupling constants of Z-configured protons (3JH–H = 12 Hz). Notably, the derivative 3c did not react any further under these conditions (cf. Supporting

[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

• alkene 59 and its transformation to 54. For the reaction performed at 25 °C, the principle observations remained the same except that the reaction speed was remarkably lower. Nevertheless, these experiments allowed to conclude that the rearrangement proceeded via a two-step mechanism, with the first step

• , leading to intermediate I, and the overall transformation proceeded with remarkable stabilization. In the next step, dissociation of the C−O bond occurred through transition state II, finally leading to alkene III. The activation energy for the C−O bond cleavage in 20, a tertiary alcohol, was similar to

• investigated. On the other hand, the complex of 17 and AlCl3 underwent C–O bond cleavage and γ-hydrogen atom abstraction, with an activation barrier of +16.5 kcal/mol, which led to the corresponding alkene, with a stabilization energy of −13.5 kcal/mol. The loss of AlCl3/H2O afforded the β,γ-alkenylphosphine

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• confirmed that the Nicholas reaction can be carried out in a nucleoside presence, leading to a divergent synthesis of novel metallo-nucleosides enriched with alkene, arene, arylketo, and heterocyclic functions, in the deoxy and ribo series. Keywords: alkynes; 5-alkynyluridines; C–C-bond formation; dicobalt

• , has been introduced into the repertoire of nucleosides modifications. The reaction of dicobalt hexacarbonyl propargylic alcohol uridine derivatives has been validated with diverse C-nucleophiles. By this means, alkene, arene, arylketo, and heterocyclic functions can be introduced onto metallo

A chiral self-sorting photoresponsive coordination cage based on overcrowded alkenes

• Constantin Stuckhardt,
• Diederik Roke,
• Wojciech Danowski,
• Edwin Otten,
• Sander J. Wezenberg and
• Ben L. Feringa

Beilstein J. Org. Chem. 2019, 15, 2767–2773, doi:10.3762/bjoc.15.268

• between the three isomers. Two of the isomers were able to form host–guest complexes opening up new prospects toward stimuli-controlled substrate binding and release. Keywords: coordination cages; molecular motors; molecular switches; overcrowded alkene; palladium; Introduction Supramolecular

• -pyridinylboronic acid with an E/Z mixture of reported overcrowded alkene precursors [51] (see Supporting Information File 1 for full experimental details). Heating a 2:1 mixture of ligands (S,S)-Z-1 or (S,S)-E-1 with Pd(NO3)2 in acetonitrile at reflux led to the quantitative formation of cage Pd2(stable Z-1)4 or

• (stable E-1)4 generated by irradiation of Pd2(unstable Z-1)4 at 365 nm. Cage formation of overcrowded alkene switches E/Z-1 and their isomerization behavior. Note that the intermediate unstable E-1 is not shown; due to the low barrier of thermal helix inversion and therefore fast isomerization to the

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• attacking of nucleophilic partners, followed by a protodemetalation step to form the alkene motif (Scheme 1, path a) [9][10][11]. However, the formation of a silver carbene intermediate, which could be generated usually from relevant diazo precursors [12][13][14], appears to be an unusual event in silver

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• additional cyclisation through compound rac-53 (Scheme 9). This is initiated by the acid employed in the second step of the synthesis. Thus, the ketone is protonated and the highly electrophilic carbon atom reacts with the alkene moiety. The resulting tertiary carbocation undergoes a 1,2-methyl shift to

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• the important anticancer drug suberoylanilide hydroxamic acid (SAHA) from its α,ß-didehydro derivative is described. The didehydro derivative is obtained through a cross metathesis reaction between a suitable terminal alkene and N-benzyloxyacrylamide. Some of the didehydro derivatives of SAHA were

• derivative 11a [11]. Cross metathesis (CM) between a terminal alkene and an α,ß-unsaturated carbonyl compound (or similar electron-deficient alkenes) has been used to prepare functionalized alkenes in several occasions [18][19][20]. We have recently reported the CM of a terminal alkene with a hydroxamic acid

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• catalysis has proved its effectiveness for numerous transformations involving unsaturated bond activation (allene, alkyne, alkene) [11][12][13][14][15][16][17], radical-based reactions [18][19][20] and several applications in asymmetric reactions [21][22]. This successful chemistry was usually conducted in

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• electron-rich unsaturated bonds (arene, alkene, or alkyne), or a substrate having a nucleophilic and labile bond (e.g., C−Si, C−Sn, and C−B), while the electrophile is the fluorination reagent (Scheme 1b). As shown in Scheme 1d, many nucleophilic and electrophilic fluorination reagents have been developed

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• these doublets as 2 protons suggested that the exocyclic alkene was present in only one of the products. In the literature, this exocyclic alkene in β-sesquiphellandrene is observed at 4.72 ppm as a multiplet [39]. A triplet at 5.39 ppm that integrates for 2 protons can be assigned to H10 in both 26 and

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• ) as alkene component had detrimental effects on the yields in the synthesis of 2d, 2f and 2h. Intermediates 5a and 5b were accessible from 3a and 3b via Suzuki–Miyaura or Stille coupling [34]. Biology The influence on deacetylase activity of three human sirtuin isoforms (Sirt1–3) was determined in a

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• enabled the assignment of these signals to the 1,2-disubstituted alkene moiety. Thus, the NMR data presented above indicate the presence of an isolated spin system, O–CH2–CH–CH2–CH=CH. A similar analysis of the remaining complex multiplets at 1.56, 1.77, and 1.93 ppm as well as their correlation with the

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• (Figure S37, Supporting Information File 1) and previously reported congener 5 were almost identical, while 4 displayed no significant UV–vis absorptions, suggesting the absence of both the ester and alkene moieties. This was confirmed by the analysis of the 1H and 13C NMR data for 4 (Table 1), which

• revealed the absence of ester and alkene resonances and the presence of three hydroxylated methylenes at C-12 (δC 62.2; δH 3.79 and 3.65), C-14 (δC 69.8; δH 3.90 and 3.36) and C-15 (δC 62.9; δH 3.77 and 3.47), and one hydroxylated quaternary carbon at C-2 (δC 88.1). This suggested 4 was related to 5, but

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• and two radical C1 synthons, CO and sulfonyl oxime ethers, is known to be feasible [23][24][25], we were tempted to explore a novel class of four-component radical reaction [26][27][28] incorporating a xanthogenate, an alkene, CO, and a sulfonyl oxime ether (Scheme 1, reaction 2). This paper reports

• Gel 60N (spherical, neutral, 40–50 μm)) and, if necessary, were further purified by recycling preparative HPLC (Japan Analytical Industry Co. Ltd., LC-918) equipped with GPC columns (JAIGEL-1H + JAIGEL-2H columns) using CHCl3 as eluent. Xanthogenate 1a,b [20], 1c [36], alkene 2c [37], and oxime ester

• mechanism. Concept: Alkene difuctionalization by four-component radical reaction using xanthates, alkenes, CO and sulfonyl oxime ethers. Four-component coupling reaction of ethyl 2-((ethoxycarbonothioyl)thio)acetate (1a), 1-octene (2a), CO, and sulfonyl oxime ether 3a under radical conditionsa. Supporting

A golden opportunity: benzofuranone modifications of aurones and their influence on optical properties, toxicity, and potential as dyes

• Joza Schmitt and
• Scott T. Handy

Beilstein J. Org. Chem. 2019, 15, 1781–1785, doi:10.3762/bjoc.15.171

• –vis spectrum; Introduction Aurones are a fascinating minor sub-family of the flavonoid natural products [1][2]. While they feature the same C15 composition as other flavonoids, the skeleton is quite different, featuring a benzofuranone connected to an aromatic ring via an exocyclic alkene. This

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• along with 8% of the alkene 22. It is proposed (Scheme 5) that these products arise from stepwise formation of the cyclopropylcarbinyl cation 23. This cation can rearrange via migration of bond a to give the cyclobutyl cation 24. The cis-nature of the phenyl group and the hydrogen in cation 23

• product, the alkene 22. Interestingly, formation of the γ-silyl cation 24 is preferred over the β-silyl cation 25. Reaction of the isomeric mesylate 20 in CD3CO2D gives the same rearranged products 21 and 22. These products are accounted for mechanistically in Scheme 6. The initially formed

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• moiety (Scheme 13) [51]. Before conversion of the chloromethyl group into a phosphonium salt the chiral auxiliary was removed. The reaction of the ylide (R)-45 prepared from the chloride (R)-44 with benzaldehyde afforded (E)-alkene (S)-46 which after hydrogenation and basic hydrolysis gave ʟ

• corresponding ketone with a NaBH4/ZnCl2 mixture. Treatment of (2S,1'R,1''R)-98 with LiAlH4 to secure the trans-configured alkene, protection of the hydroxy group and the regioselective aziridine ring opening led to the formation of the acetate (2S,3R,1'R)-99. After basic hydrolysis the oxazolidin-2-one (2S,3R,1

• secured in the starting aldehyde introduction of the two others required cis-dihydroxylation of the Z-alkene 111. The highest diastereoselectivity (99:1) was observed at −10 °C providing the aziridine diol (2S,1'S,2'R,1''R)-112 as a major diastereoisomer. The regioselective aziridine ring opening combined

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• reaction of allene 1a with benzene resulted in the formation of alkene Z-11a, as a product of intermolecular hydroarylation of the carbon–carbon double bond (Table 2, entries 4–6). This reaction required 2.1 equivalents of AlCl3, 1.05 equivalents of benzene and five minutes at room temperature (Table 2

• /or indanes 12 (Table 3). Thus, in reactions with benzene, only cis-alkene Z-11b was obtained in 88% yield (Table 3, entry 1). The sole formation of alkenes E-11g, Z-11h and Z-11i, and E/Z-11l was also observed in reactions with 1,2-dimethoxybenzene (veratrole) (Table 3, entry 6), fluorobenzene (Table

• complex mixtures of oligomeric compounds. In the same reaction with benzene, allene 1b afforded alkene Z-11n in high yield (Scheme 5). The use of morpholine for quenching of the superacidic reaction mixture gave amide Z-11o in the reaction of 1a with benzene (Scheme 6). We also conducted a large-scale one