Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• increase the selectivity for the C6 product, dissolved nickel and iron redox mediators have been used [48][53][54]. The need for such organometallic complexes could be eliminated by direct electrocarboxylation on nickel or stainless steel cathode surfaces [49][50]. Substrates with an internal conjugated

A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• cancerous rather than squamous tissues [1]. δ-Aminolevulinic acid (1, ALA, Scheme 1) is a δ-amino acid precursor in the cellular biosynthesis of heme [2]. The penultimate step in this biosynthetic cycle is the iron chelation of protoporphyrin IX (PpIX), a porphyrin photosensitizer (PS) which was shown to be

• molecular multiplicity of 2 that is solely responsible for the PpIX fluorescence enhancement, but either an augmented cell entry or the inhibition of ferrochelatase-catalyzed iron insertion to form non-fluorescent iron-complexed heme [19] (possibly due to the existence of PpIX-CD moieties). These

Oligomerization of optically active N-(4-hydroxyphenyl)mandelamide in the presence of β-cyclodextrin and the minor role of chirality

• Helmut Ritter,
• Antonia Stöhr and
• Philippe Favresse

Beilstein J. Org. Chem. 2014, 10, 2361–2366, doi:10.3762/bjoc.10.246

• .10.246 Abstract The oxidative oligomerization of a chiral mandelamide derivative (N-(4-hydroxyphenyl)mandelamide, 1) was performed in the presence of horseradish peroxidase, laccase and N,N'-bis(salicylidene)ethylenediamine-iron(II) to obtain chiral oligophenols 2. The low enantioselectivity of the

• the oligomerization of substituted electron-rich phenols in the presence of oxidizing agents [3][4]. In addition to that, N,N'-bis(salicylidene)ethylenediamine-iron(II) (iron(II)-salen) represents an alternative catalyst for oxidative coupling reactions of phenol derivatives [5]. The use of β

• from horseradish or iron(II)-salen were used as catalysts. The obtained yellow powdery oligomers 2 show high solubility in many commonly used organic solvents like acetone, THF, ethanol, methanol, acetonitrile and 1,4-dioxan. Because of the broad signals of the oligomers 2 in the 1H NMR spectra the

N–O Cleavage reactions of heterobicycloalkene-fused 2-isoxazolines

• Jaipal R. Nagireddy,
• Geoffrey K. Tranmer,
• Emily Carlson and
• William Tam

Beilstein J. Org. Chem. 2014, 10, 2200–2205, doi:10.3762/bjoc.10.227

• , ammonium formate) [22], as well as the combination of Pd(OH)2 with H2. However, none of these palladium-mediated attempts resulted in a clean transformation. Trials involving zinc dust in aqueous AcOH, as well as iron and ammonium chloride in aqueous EtOH at various temperatures also failed [23][24

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• -diarylindoles were successfully reacted with N-Boc-THIQ to furnish 1,2,3-trisubstituted indoles as target compounds. Furthermore, regioselective N-arylation of protected and unprotected 1-(indol-3-yl)-THIQs was successfully conducted using either simple iron or copper salts as catalysts. Keywords: Buchwald

• –Hartwig coupling; C–C coupling; C–H functionalization; iron catalysis; regioselective arylation; Introduction 1,2,3,4-Tetrahydroisoquinolines (THIQs) are common substructures in natural products [1]. The structural motif of 1-(indol-3-yl)-THIQ is also found in compounds with biological activity, for

• -(1,2-diarylindol-3-yl)-N-protected-THIQs 1 by employing palladium, copper, and iron-catalyzed methods. Results and Discussion Catalyst price and availability were important considerations for selecting transformations to be used in this project. Whenever possible, iron or copper catalysis was

Comparing kinetic profiles between bifunctional and binary type of Zn(salen)-based catalysts for organic carbonate formation

• Carmen Martín and
• Arjan W. Kleij

Beilstein J. Org. Chem. 2014, 10, 1817–1825, doi:10.3762/bjoc.10.191

• , nontoxic and earth-abundant metal-based complexes based on aluminum [24] and iron [25] amino-triphenolate complexes. Additionally, salen-based Zn complexes were also found to be rather efficient catalyst for this transformation. More specifically, these systems relate to the Zn(salphen) family of complexes

• dimetallic aluminum complex 5 (Figure 1) was utilized [40]. Another interesting example was described by Rieger et al. who used a single-component catalyst 6 based on iron (Figure 1) for which a second-order rate dependence was determined indicating a dimetallic reaction mechanism [41]. Of further importance

• Rieger et al. for iron catalyst 6 [41]. This experimental evidence suggests that in the rate-determining step one molecule of the Zn complex 2 may activate the substrate through coordination, while the iodide anion of a second molecule of 2 attacks the coordinated epoxide (Scheme 4). This mechanistic

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• trimethylsilylazide and iron(III) chloride (Scheme 3) [54]. The β-configuration of the azide was confirmed by comparison of coupling constants with literature data [55]. With both head groups and tails in hand, high-throughput CuAAC reactions were employed to synthesise amphiphiles using a 24-vial array. Azido-sugars

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• ]. Basing on the structure of streptopyridine A, a 3-pentenyl side chain seemed to be most likely. Coupling of (E)-3-pentenylmagnesium bromide with 2-chloropyridine under Fürstner conditions with iron(III) acetylacetonate as catalyst [17] yielded (E)-2-(pent-3-enyl)pyridine (8) that proved to be identical

• of the volatiles by CLSA. Synthesis of reference compounds The compounds 6–8 were synthesized after the standard procedure for iron-catalyzed aryl–alkyl cross-coupling described by Fürstner et al [17]. 2-Propylpyridine (6): Yield (1.01 g, 8.35 mmol, 61%); Rf (pentane/Et2O 5:1) 0.2; UV (CH2Cl2) λmax

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• ][94][95][96], palladium [97][98][99] or nickel [100][101][102][103][104] complexes. Other catalysts that have been less investigated are iron [105][106][107], rhodium [108][109][110], lanthanides [111][112][113][114], copper [115] and alkaline-earth metals [114][116]. The catalyst activates either the

On the mechanism of photocatalytic reactions with eosin Y

• Michal Majek,
• Fabiana Filace and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2014, 10, 981–989, doi:10.3762/bjoc.10.97

• with arenediazonium salts are often more selective than traditional methods such as copper(II)-mediated Meerwein arylations [11] or protocols employing stoichiometric iron(II) or titanium(III) reductants in aqueous media [12][13][14]. This renaissance of arene diazonium chemistry has recently led to

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• vinyl bromide 227 (see Scheme 27) formation of the corresponding Grignard species was acomplished, followed by addition to organoiron complex 228 to give (pentenediyl)iron complex 229. Oxidation led to the formation of the desired divinylcyclopropane, followed by reduction of the ester to the desired

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• , this compound is currently in phase III clinical trials [77][78][79][80][81]. The mechanism of antimalarial action of peroxides is unusual for pharmaceutical chemistry. According to the commonly accepted mechanism, peroxides diffuse into Plasmodium-infected erythrocytes, and the heme iron ion of the

New syntheses of 5,6- and 7,8-diaminoquinolines

• Maroš Bella and
• Viktor Milata

Beilstein J. Org. Chem. 2013, 9, 2669–2674, doi:10.3762/bjoc.9.302

• -nitroquinoline in a low yield (14%). The latter was reduced with iron in acetic acid to 7-aminoquinoline which was subsequently tosylated, nitrated in position 8 and detosylated to yield 7-amino-8-nitroquinoline. In the final step, the reduction of aminonitroquinoline with SnCl2·2H2O provided 7,8

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• regenerates the copper catalyst, thus allowing the catalytic turnover (Figure 1). 2.2 Iron catalysis Similarly to the work of J. Hu and colleagues using copper catalysis, the group of Z.-Q. Liu reported on the decarboxylative difluoromethylation of α,β-unsaturated carboxylic acids. However, the latter used

• iron(II) sulfate as catalyst and zinc bis(difluoromethanesulfinate) as the fluoroalkyl transfer reagent. A handful of β-difluoromethylstyrenes were obtained in moderate yields and with complete diastereoselectivity (Scheme 4) [62]. 3 Catalytic perfluoroalkylation The transition metal mediated

• as the major products. F. Minisci and coworkers also obtained similar results when using a catalytic iron(III) salt in the presence of tert-butyl peroxide as oxidant. T. Yamakawa et al. applied this Fenton-based generation of perfluoroalkyl radicals for the trifluoromethylation of uracil derivatives

Iron-catalyzed decarboxylative alkenylation of cycloalkanes with arylvinyl carboxylic acids via a radical process

• Jincan Zhao,
• Hong Fang,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2013, 9, 1718–1723, doi:10.3762/bjoc.9.197

• ) in the presence of iron(II) chloride tetrahydrate (20 mol %) and 2.0 equiv of di-tert-butyl peroxide (DTBP) as the oxidant at 120 °C under nitrogen, which provided the expected (E)-(2-cyclohexylvinyl)benzene (3a), but in a moderate 54% yield (Table 1, entry 1). The use of aqueous TBHP as oxidant

• instead of DTBP reduced the yield to only 38% (Table 1, entry 2). With the help of 1,10-phenanthroline (30 mol %) as the ligand, the yield could be slightly improved to 68% (Table 1, entry 3). Iron(III) acetylacetonate provided a superior yield (91%) compared to the other Fe salts such as FeCl3, ferrocene

• °C), decreased the yield to 63%, 69% and 79%, respectively (Table 1, entries 12–14). The reaction did not proceed without the iron catalyst or DTBP (Table 1, entries 15 and 16). We then examined the substrate scope and limitation of the procedure by reacting cyclohexane with a variety of substituted

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• began with the acetylation of 4-chloro-3-nitroaniline (9) followed by reduction of the nitro group using iron and hydrochloric acid to generate aniline 10. The azido group was introduced by diazotization/azidation to provide 11. Deacetylation with potassium hydroxide revealed aniline 12, which was then

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• Daisuke Shigeoka Takuma Kamon Takehiko Yoshimitsu Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan 10.3762/bjoc.9.99 Abstract An iron(II)-mediated aminohalogenation of a cyclopentenyl N-tosyloxycarbamate provided new access to the key

• intermediate for the synthesis of (−)-agelastatin A (AA, 1), a potent antiproliferative alkaloid. The present synthetic endeavour offered an insight into the mechanism underlying the iron(II)-mediated aminohalogenation of N-tosyloxycarbamate, in which the radical properties of the N–iron intermediates in the

• redox states were operative. Keywords: agelastatin; aminohalogenation; iron(II); free radical; natural product synthesis; Introduction Marine organisms often produce bioactive substances that potentially serve as attractive resources for drug discovery. (−)-Agelastatin A (AA, 1), a cytotoxic alkaloid

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• compounds. The formation of C–S bonds can also be accomplished in good to excellent yields by transition-metal catalysis [10][11], mainly using palladium [12], copper [13][14][15][16], nickel [17][18] and iron [19][20] salts. Aryl coupling reactions employing different palladium species as catalysts

• represent the most extensively studied approaches to form new CAr–S bonds [21][22][23]. Nevertheless, copper or iron-mediated coupling reactions have become a convenient alternative to the expensive Pd/ligand systems due to the lower cost of the former, its stability, and the ready availability of the

Synthesis of SF₅-containing benzisoxazoles, quinolines, and quinazolines by the Davis reaction of nitro-(pentafluorosulfanyl)benzenes

• Petr Beier and
• Tereza Pastýříková

Beilstein J. Org. Chem. 2013, 9, 411–416, doi:10.3762/bjoc.9.43

• play a role here. These results indicate that the reaction scope shows limitations and the electronic properties of the starting substrates have to be finely tuned for efficient reaction. The benzisoxazoles 7 and 8 were reduced to ortho-aminobenzophenones 10 and 11 in excellent yields by using iron

• arylacetonitriles containing electron-neutral or electron-donor groups. Reductions of the benzisoxazoles with iron powder in acetic acid provided high yields of SF5-containing ortho-aminobenzophenones, which underwent condensation reactions to quinolines or quinazolines. This methodology provides straightforward

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39

• , Apartat de Correus 22085, 46071 València, Spain Institute of Condensed Matter and Nanosciences, MOST – Inorganic Chemistry, Université Catholique de Louvain, Place L. Pasteur 1, 1348 Louvain la Neuve, Belgium 10.3762/bjoc.9.39 Abstract The article deals with coordination compounds of iron(II) that may

• pressure are subjects of two separate sections. The major part of this account concentrates on selected spin crossover compounds of iron(II), with particular emphasis on the chemical and physical influences on the spin crossover behavior. The vast variety of compounds exhibiting this fascinating switching

• phenomenon encompasses mono-, oligo- and polynuclear iron(II) complexes and cages, polymeric 1D, 2D and 3D systems, nanomaterials, and polyfunctional materials that combine spin crossover with another physical or chemical property. Keywords: cages; iron(II) coordination compounds; physical techniques

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• ]. Recently, Ready reported an intriguing iron-catalyzed carbomagnesiation of propargylic and homopropargylic alcohols 2b to yield syn-addition intermediates 2c with opposite regioselectivity (Scheme 7) [64]. They assumed that the key organo-iron intermediate 2A underwent oxygen-directed carbometalation to

• ]. Nakamura and co-workers discovered that an addition of iron salt enhanced the carbometalation of cyclopropenone acetal with organomagnesium and -zinc species (Scheme 17) and applied the reaction to enantioselective carbozincation (Scheme 18) [82][83]. The scope was wide enough to use phenyl-, vinyl-, and

• methylmagnesium reagents or diethylzinc and dipentylzinc reagents. It is noteworthy that the reaction in the absence of the iron catalyst did not proceed at low temperature and gave a complex mixture at higher temperature (up to 65 °C). A hydroxymethyl group also showed a significant directing effect in the

Tandem aldehyde–alkyne–amine coupling/cycloisomerization: A new synthesis of coumarins

• Maddi Sridhar Reddy,
• Nuligonda Thirupathi and
• Madala Haribabu

Beilstein J. Org. Chem. 2013, 9, 180–184, doi:10.3762/bjoc.9.21

• , cobalt, iridium and iron. Similarly, cycloisomerization of alkynols and alkynamines has also been an attractive approach for the synthesis of various known and new heterocyclic frameworks [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Various alkynophilic catalysts such as

Iron-containing mesoporous aluminosilicate catalyzed direct alkenylation of phenols: Facile synthesis of 1,1-diarylalkenes

• Satyajit Haldar and
• Subratanath Koner

Beilstein J. Org. Chem. 2013, 9, 49–55, doi:10.3762/bjoc.9.6

• conditions”. On further exploration of the use of iron-based mesoporous aluminosilicate catalyst in the direct alkenylation of arenes, we have succeeded in vinylation of various phenols with different phenylacetylenes. In this paper we report a convenient method for the alkenylation of phenols with aryl

• -substituted alkynes under mild conditions. Results and Discussion MCM-41 and Al-MCM-41 were prepared according to the procedure described in our earlier report [33]. The incorporation of iron(III) was achieved in a similar way [33]. The mesoporous patterns of MCM-41, Al-MCM-41 and Fe-Al-MCM-41 were

• established from the small-angle XRD patterns (see Supporting Information File 1). The BET surface area and the pore width of Fe-Al-MCM-41 were found to be 753 m2/g and 25.83 Å, respectively. The aluminium and iron contents of the Fe-Al-MCM-41 catalyst were estimated by AAS method and found to be 5.5 wt % and

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• ) using PRIME [35]. Finally, binding scores were computed by using both Glide XP and the MM/GMSA method. Compound 4 was predicted to bind in a similar fashion as (R)-5, with the 4-pyridyl ring chelating the heme-iron atom and the tolyl ring at P2 contacting many of the same residues (e.g., Try103, Phe110

• TcCYP51. For 4, the ligand, the protein, and the heme group are shown in green, pink, and grey, respectively. For (R)-5, the ligand, the protein, and the heme group are shown in cyan, purple, and white, respectively. Heme-iron chelation and hydrophobic binding interactions dominate in the models. (B

New enzymatically polymerized copolymers from 4-tert-butylphenol and 4-ferrocenylphenol and their modification and inclusion complexes with β-cyclodextrin

• Adam Mondrzyk,
• Beate Mondrzik,
• Sabrina Gingter and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 2118–2123, doi:10.3762/bjoc.8.238

• subsequent click chemistry with N3-β-CD. The covalently bound cyclodextrin moiety and the covalently bound Fc or tert-butyl group form host/guest complexes as proven by DLS measurement. The cyclic voltammetry data shows that the central iron atom of the Fc moiety is present in the copolymer and can be