One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• via the oxaphosphetane 92 intermediate by treating 4,5-benzotropone (11) with (diphenylmethylene)(phenyl)phosphine oxide (91) generated thermally or photochemically from 90 [82]. Furthermore, dimeric byproduct 93 is also formed under photochemical conditions. 2.2.2. Ring expansion reactions via a

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• derivative of iodosodilactone 6-(3,5-bis(trifluoromethyl)phenyl)-1H,4H-2aλ3-ioda-2,3-dioxacyclopenta[hi]indene-1,4-dione (abbreviated as FPID, Figure 1) [29]. In combination with tris(4-methoxyphenyl)phosphine [(4-MeOC6H4)3P], FPID can efficiently mediate peptide coupling reactions within 30 minutes to

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• , the 3'-amine was protected with an azidomethyloxycarbonyl (Azoc) protecting group. This protecting group can be rapidly removed under non-denaturing conditions after incorporation by the complementary nucleotide using the Staudinger reaction with a water-soluble phosphine (Figure 11). This protocol

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• fluoroalkylated pyruvates is shown with dimethylzinc as a methylating reagent in the presence of a copper catalyst bearing a chiral phosphine ligand. This is the first catalytic asymmetric methylation to synthesize various α-fluoroalkylated tertiary alcohols with CF3, CF2H, CF2Br, and n-CnF2n+1 (n = 2, 3, 8

• ) groups in good-to-high yields and enantioselectivities. Axial backbones and substituents on phosphorus atoms of chiral phosphine ligands critically influence the enantioselectivity. Moreover, the methylation of simple perfluoroalkylated ketones is found to be facilitated by only chiral phosphines without

• copper. Keywords: asymmetric methylation; chiral phosphine ligand; copper catalyst; dimethylzinc; trifluoropyruvate; Introduction The introduction of fluorine atoms into organic compounds plays an important role in the discovery of lead candidates with unique biological and physicochemical properties

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• -carboxyethyl)phosphine (TCEP, Figure 6) leaving all other protecting groups intact. The resulting hemi-(S,O)-acetal at the nucleotiode 3'-terminus is spontaneously degraded into the alcohol and thioformaldehyde, thus delivering the trimer with free 3'-OH group for subsequent phosphitylation. The detailed

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• high background. The masking of fluorophores by a more stable group, such as azides, is more attractive. Unfortunately, the phosphine probe generally required for the unmasking of the azide probe is susceptible to rapid aerobic oxidation. Accordingly, new developments in this area are still required

• . One promising example is the release of fluorophores by a phosphine-free photocatalyzed reduction of a self-immolative azide-based linker [105]. Single-labeled PNA probes with additional interacting partners PNA-based strand displacement probes Strand displacement probes consist of a fluorescence

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• deprotection by catalytic hydrogenation furnished lipid A 31. Alternatively, the lactol 30 was phosphitylated by application of the phosphoramidite procedure with (benzyloxy)[(N-Cbz-3-aminopropyl)oxy](N,N-diisopropylamino)phosphine in the presence of 1H-tetrazole and subsequent oxidation with dimethyldioxirane

Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

• Aymen Skhiri,
• Ridha Ben Salem,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2017, 13, 2862–2868, doi:10.3762/bjoc.13.278

• heteroarylations with a variety of heteroarenes using a phosphine-free palladium catalyst. Results and Discussion First, we examined the influence of the reaction temperature, using DMA as solvent, KOAc as base and 2 mol % Pd(OAc)2 as catalyst (Table 1). We had previously observed that these reaction conditions

• , whereas thiophene or pyrroles gave the desired products in low yields. Conversely, 2,5-dibromoselenophene was successfully coupled with both thiazoles and thiophenes in the presence of phosphine-free Pd(OAc)2 catalyst precursor and KOAc as inexpensive base, affording the desired 2,5-diheteroarylated

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• of an halogen bond between the positive electrostatic potential on the outer side of the chlorine atom and the lone pair of the phosphorus atom of the phosphine. This phenomenon indeed triggered the cleavage of the S–Cl bond, producing chlorophosphonium sulfinate 40, which was then readily converted

• previous reports, the proposed mechanism does not include the free phosphine as the reducing agent, but rather iodotriphenylphosphonium iodide 42. This species was supposedly generated from PPh3 and I2, itself issued from the reaction of CF3SO2Cl, PPh3 and NaI. Species 42 was able to reduce CF3SO2Cl

• indoles, except that the nature of the phosphine as well as the stoichiometry between CF3SO2Cl and PCy3 prevented the reduction of formed CF3SOCl and therefore allowed its direct reaction with the substrate (Scheme 38). 4 Chlorination Sparingly, CF3SO2Cl was employed as a chlorinating agent. The first

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• polymeric phosphonium salts that were amorphous and unable to crystallize. Such products may be formed as a result of a subsequent Michael-like addition of the starting phosphine to the initially obtained vinylphosphonium salt 1 (Scheme 3). The formation of the expected salt was faster than the side

• –89% and a high stereoselectivity (Scheme 6) [14][15]. The proposed mechanism of this reaction is as described in Scheme 7 [14][15]. Oxidative addition of the vinyl triflate to the catalyst results in complex 6 that upon reductive elimination (an added phosphine) provides the vinylphosphonium salt and

Synthesis and photophysical properties of novel benzophospholo[3,2-b]indole derivatives

• Mio Matsumura,
• Mizuki Yamada,
• Atsuya Muranaka,
• Misae Kanai,
• Naoki Kakusawa,
• Daisuke Hashizume,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2017, 13, 2304–2309, doi:10.3762/bjoc.13.226

• -dimethylaniline. Using the obtained benzophosphole-fused indole as a common starting material, simple modifications were carried out at the phosphorus center of the phosphole, synthesizing various functionalized analogs. The X-ray structure analysis of trivalent phosphole and phosphine oxide showed that the fused

• tetracyclic moieties are planar. The benzophosphole-fused indoles, such as phosphine oxide, phospholium salt, and borane complex, exhibited strong photoluminescence in dichloromethane (Φ = 67–75%). Keywords: benzophospholo[3,2-b]indole; DFT calculation; molecular structure; phosphole derivatives

• benzophosphole-fused indole derivative and its various functionalized analogs such as the corresponding phosphine oxide, phosphonium salt, and borane–phosphine complex. Results and Discussion The synthesis of the parent tetracyclic molecule 10-phenyl-[1]benzophospholo[3,2-b]-N-methylindole (3), is shown in

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• induced the silylation of diethyl phosphonate but also the phosphoramidate and the phosphinate functional groups. Other phosphonic acids possessing different functionalities including phosphine 56 [183], trimethylsilyl 57 [184], diazo 58 [185] or styrene 59 [186] moieties were also prepared efficiently

• produce compound 98 [213] (Figure 28A). A second example corresponds to the nucleophilic addition of N-heterocyclic phosphine 99 to a nitroalkene (phospho-Michael reaction) as shown in Figure 28B. The thiourea unit in 99 plays a crucial role by assuming intramolecular interaction with the nitro function

• )phosphine 108 was hydrolysed into the tris-phosphonic acid 109 using water and HCl up to pH 1. Of note, the same reaction that engaged diethyl 4-fluorophenylphosphonate instead of the 4-fluorophenylphosphonodiamide 107 is inefficient (3% yield) due to the monohydrolysis of the phosphonate. 6. Direct method

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• this protocol. Different organophosphorus compounds including phosphine oxides, phosphinate ester, and phosphonate diester underwent C–P bond formation to give 22–94% of yield (Scheme 42). This method was also found to be applicable in gram scale synthesis with excellent yield. Mechanistically they

Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• proceeds via base-promoted propargyl–allenyl rearrangement followed by cyclization and allyl migration. Phosphine-substituted indoles can be synthesized by a similar strategy. Keywords: allyl migration; benzothiophene; indole; metal-free; propargyl-allenyl; Introduction Heterocycles are frequently found

• propargyl–allenyl rearrangement [17][18][19][20][21][22][23][24][25][26][27] and an allyl migration [32][33][34] (Scheme 1). In addition, phosphine-substituted indole derivatives could also be conveniently constructed by a similar strategy. This method not only avoids the use of transition metal catalysts

• allyl migration (Scheme 2). Phosphine-substituted indole derivatives were obtained in moderate yield (Figure 3, 4a–c). Conclusion In summary, we have developed an expedient route for the construction of benzothiophene and indole derivatives via propargyl–allene rearrangement and allyl migration. The

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• a bulky monodentated phosphine (Scheme 1, reaction 1) [32]. More recently, important efforts have been made in order to develop new methodologies towards more effective and selective catalytic systems, such as the introduction of highly active N-heterocyclic carbene (NHC) catalysts reported by

Ni nanoparticles on RGO as reusable heterogeneous catalyst: effect of Ni particle size and intermediate composite structures in C–S cross-coupling reaction

• Debasish Sengupta,
• Koushik Bhowmik,
• Goutam De and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 1796–1806, doi:10.3762/bjoc.13.174

• properties [14]. The Ni-catalyzed C–S cross-coupling reactions generally involved Ni salts [15][16][17][18], Ni–phosphine complexes [19][20][21], or Ni–NHC complexes [22][23], although the actual catalyst is believed to be a Ni(0)/Ni(I) species [16][17][18][19][20][21]. NiO supported on zirconia (NiO–ZrO2

An efficient Pd–NHC catalyst system in situ generated from Na₂PdCl₄ and PEG-functionalized imidazolium salts for Mizoroki–Heck reactions in water

• Nan Sun,
• Meng Chen,
• Liqun Jin,
• Wei Zhao,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 1735–1744, doi:10.3762/bjoc.13.168

• modifying traditional palladium–phosphine catalysts by grafting various hydrophilic substituents on phosphine ligands [18][19][20][21][22][23][24][25][26][27]. However, most of these phosphine ligands are air sensitive and required tedious work to preparation. In addition, the easy dissociation of common P

• –Pd bonds under aqueous reaction conditions often restricted the reuse of the catalyst and led to undesired residues. Therefore, in recent years, efforts have been turned to the development of water-soluble non-phosphine ligands [28][29][30][31][32][33][34]. In this context, N-heterocyclic carbenes

• (NHCs) have been recognized as the preferable candidates [35][36]. In contrast to common phosphine- and nitrogen-based ligands, NHCs exhibit stronger σ-donating and weaker π-accepting properties, which make the corresponding Pd–NHC complexes more air and water stable. Furthermore, the convenient

Encaging palladium(0) in layered double hydroxide: A sustainable catalyst for solvent-free and ligand-free Heck reaction in a ball mill

• Wei Shi,
• Jingbo Yu,
• Zhijiang Jiang,
• Qiaoling Shao and
• Weike Su

Beilstein J. Org. Chem. 2017, 13, 1661–1668, doi:10.3762/bjoc.13.160

• , which is desirable in the fields of chemistry, materials science, biology, pharmaceutical, dyestuff, agriculture and so forth [8][9][10][11][12]. The homogeneous palladium salts along with phosphine- or nitrogen-based ligands were employed as the traditional catalyst systems not only in solution-based C

Direct catalytic arylation of heteroarenes with meso-bromophenyl-substituted porphyrins

• Alexei N. Kiselev,
• Olga K. Grigorova,
• Alexei D. Averin,
• Sergei A. Syrbu,
• Oskar I. Koifman and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2017, 13, 1524–1532, doi:10.3762/bjoc.13.152

• partially reduced by the phosphine ligand. The application of another catalytic system with Pd(0), Pd(dba)2/DavePhos (20:22 mol %, dba = dibenzylideneacetone) together with a 100% excess of benzothiazole was more successful as it afforded 32% yield of compound 3 (Table 1, entry 2); it is interesting that

• catalytic conditions proposed by Osuka for the β-arylation of porphyrins with bromoarenes [28] and investigated the reactions of the zinc porphyrinates 1 and 2 with benzoxazole (2 equiv) or benzothiazole (2 equiv) in the presence of Pd(OAc)2 (20 mol %) without phosphine ligand with pivalic acid as an

• without any additional ligand was shown to be advantageous over catalytic systems with phosphine ligands. Osuka also used this approach for β-arylation of porphyrins. In this ligandless reaction the Pd(0) species from palladium acetate could be provided by the traces of amine present in DMA, and the

1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

• Jakub Adamek,
• Roman Mazurkiewicz,
• Anna Węgrzyk and
• Karol Erfurt

Beilstein J. Org. Chem. 2017, 13, 1446–1455, doi:10.3762/bjoc.13.142

• arenes can be markedly facilitated using 1-imidoalkylphosphonium salts derived from triarylphosphines with electron-withdrawing substituents such as tris(m-chorophenyl)phosphine, tris(p-chlorophenyl)phosphine and tris[p-(trifluoromethyl)phenyl]phosphine. Microwave irradiation also considerably

• salts derived from triarylphosphines with electron-withdrawing substituents such as tris(m-chorophenyl)phosphine, tris(p-chlorophenyl)phosphine and tris[p-(trifluoromethyl)phenyl]phosphine were synthesized and tested in the reaction. As expected, the phosphonium salts with a reduced Cα–P+ bond strength

• reacted with anisole and 1,3-dimethoxybenzene at much lower temperatures (Table 3, entries 3–7, 10, 11, 13, 17–19, 22 and 23). The most clear-cut results were obtained for tris[p-(trifluoromethyl)phenyl]phosphine derivatives. 1-Phthalimidoethyltris[p-(trifluoromethyl)phenyl]phosphonium tetrafluoroborate

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• of difficult-to-remove (especially in the presence of polar, unprotected products) phosphine oxide and second the need to work under anhydrous conditions. However, using stoichiometric conditions the list of glycosides available is now expansive ranging from simple phenolic glycosides to aromatic

• esters to fully unprotected nucleosides. We highlight these examples below. Due to the inherent challenges in both selective reactivity and purification of such polar products in the presence of phosphine oxide, it is not surprising that extensive optimization of conditions was necessary in all cases

• . 5.1.1 Accessing phenolic glycosides: To the best of our knowledge the first example of this methodology was applied to the synthesis of phenolic glycosides by Grynkiewicz [103][104] nearly 40 years ago. In his seminal work he discovered that by using a more reactive phosphine (PBu3), aryl glycosides

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• -supported phosphine (20 equiv) as the trapping agent. The imine is further hydrogenated at 25 °C and 20 bar pressure by using an H-cube reactor with 10% Pd/C as a catalyst [72]. Trifluoroacetylation of the amine intermediate is then carried out in a chip reactor with trifluoroacetic anhydride (in DCM) as a

• packed bed reactor control strategy will remain identical for all reagent packed reactors. The azide and the aldehyde intermediate can be mixed and preheated at the reaction temperature and passed through a phosphine-functionalized polymer packed bed reactor to obtain the imine intermediate. This imine

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

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

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• more usual strategy is the so-called “selective poisoning”, i.e., the improvement of the catalyst’s selectivity by the addition of variable, often large, amount of contaminants, either organic ligands (quinolone [65][66], phosphine [67]), carbon monoxide [68], sulfides [69], sulfoxides [70][71] defined