Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• -aminophosphonate 26 in 99% yield (Scheme 7) [34]. The reaction of isatin (27) with diethyl phosphite and benzylamine under similar conditions gave the corresponding α-aminophosphonate 28 in 90% yield together with small amounts of α-hydroxyphosphonate 29 as a side product (Scheme 8). The one-pot reaction of

• substituted isatins 30 with aniline (32) and dimethyl- or diethyl phosphite under solvent-free conditions in the presence of magnetic Fe3O4 nanoparticle-supported phosphotungstic acid as a recyclable catalyst at 80 °C furnished α-aminophosphonates 33 in yields from 80% to 98% depending on the reaction time

• and the structure of the dialkyl phosphite and isatin (Scheme 9) [35]. In this way a one-pot three-component reaction between 1-tosylpiperidine-4-one (34), aromatic amines 35 and diethyl phosphonate in the presence of magnesium perchlorate as a catalyst, under neat conditions at 80 °C afforded α

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• further reaction without purification. Aminophosphonates 3Aa–h, 3Ba–e and 3Ca–d, 3Cg have been synthesized via an aza-Pudovik reaction [22], i.e., the addition of the appropriate phosphite 2A–C to the azomethine bond of the Schiff bases 1a–h. Nevertheless, the important modifications had to be introduced

• dichloromethane solutions with a saturated aqueous sodium bicarbonate solution, which allowed to remove dimethyl phosphite. This procedure was followed by column chromatography, and, in a case of N-benzyl derivative 3Aa, triturating the product with diethyl ether until the precipitation of a solid was

• . Aminophosphonates 3Ba–e were purified by column chromatography. The most complex procedure was used to isolate and to purify the dibenzyl aminophosphonates 3Ca–d and 3Cg. The crude reaction mixtures were dissolved in small amounts of pyridine and then, treated with elemental iodine to decompose dibenzyl phosphite

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• on a report of Garcia for a related system we first evaluated Pd2(dba)3 with different phosphite ligands [39]. However, the best results were obtained with the stable catalyst Pd(PPh3)4 and depending on the solvent used, either the syn-isomer 23 or the anti-isomer 24 could be selectively obtained

Nucleic acids through condensation of nucleosides and phosphorous acid in the presence of sulfur

• Tuomas Lönnberg

Beilstein J. Org. Chem. 2016, 12, 670–673, doi:10.3762/bjoc.12.67

• Tuomas Lonnberg Department of Chemistry, University of Turku, Vatselankatu 2, FIN-20014 Turku, Finland 10.3762/bjoc.12.67 Abstract Short phosphorothioate oligonucleotides have been prepared by refluxing an equimolar mixture of thymidine and triethylammonium phosphite in toluene in the presence of

• elemental sulfur. Desulfurization and subsequent digestion of the products by P1 nuclease revealed that nearly 80% of the internucleosidic linkages thus formed were of the canonical 3´,5´-type. Keywords: H-phosphonate; nucleic acid; polymerization; phosphite; sulfurization; Introduction Arguably the most

• acid [5]. Furthermore, phosphite salts are up to 1000-fold more soluble in water than phosphate salts [6]. For these reasons, compounds of reduced phosphorus (i.e., phosphorus at oxidation state lower than +5) were first proposed to have played a role in prebiotic phosphorylation reactions as early as

Olefin metathesis in air

• Lorenzo Piola,
• Fady Nahra and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 2038–2056, doi:10.3762/bjoc.11.221

• complexes in DCM and toluene in comparison with 85; catalyst loadings were between 1 and 2 mol % and reaction times, with the synthesised complexes, were shorter than with 85. Phosphite-based catalysts In 2010, the Cazin group reported a study on the synthesis and activity of a new family of complexes (98a

• phosphite-based catalysts. Schiff base–ruthenium complexes synthesized by Verpoort. Synthesis of mixed Schiff base–NHC complexes. RCM in water and MeOH under air.a Metathesis reaction in water under air. Metathesis reactions catalysed by Scorpio-type complexes in air.a RCM with commercially available

[2.2]Paracyclophane derivatives containing tetrathiafulvalene moieties

• Laura G. Sarbu,
• Lucian G. Bahrin,
• Peter G. Jones,
• Lucian M. Birsa and
• Henning Hopf

Beilstein J. Org. Chem. 2015, 11, 1917–1921, doi:10.3762/bjoc.11.207

• The Cambridge Crystallographic Data Center via http://www.ccdc.cam.ac.uk/data_request/cif. The desulfurative dimerization of 1,3-dithiol-2-thione 6 was effected by heating it with trimethyl phosphite at 100 °C (Scheme 2). Purification of the crude reaction mixture by column chromatography resulted in

Nitro-Grela-type complexes containing iodides – robust and selective catalysts for olefin metathesis under challenging conditions

• Andrzej Tracz,
• Mateusz Matczak,
• Katarzyna Urbaniak and
• Krzysztof Skowerski

Beilstein J. Org. Chem. 2015, 11, 1823–1832, doi:10.3762/bjoc.11.198

• the first Z-selective catalysts [18][19][20][21]. Their efficiency, however, is noticeably lower than that observed for classical complexes. The second generation indenylidene catalysts with phosphite ligand (frequently reported as “Cazin-type catalysts”) bearing mixed chloride–fluoride or difluoride

Synthesis of racemic and chiral BEDT-TTF derivatives possessing hydroxy groups and their achiral and chiral charge transfer complexes

• Sara J. Krivickas,
• Chiho Hashimoto,
• Junya Yoshida,
• Akira Ueda,
• Kazuyuki Takahashi,
• John D. Wallis and
• Hatsumi Mori

Beilstein J. Org. Chem. 2015, 11, 1561–1569, doi:10.3762/bjoc.11.172

• and acetic acid in chloroform. Oxo compound 11 was then cross-coupled with 1.2 equivalents of thione 12 in triethyl phosphite to afford the racemic protected donor 13 in reasonable yield (37%). Basic hydrolysis of the acetyl protecting group afforded the racemic donor 1 in an 81% yield. The syntheses

• equiv) and the oxo-compound 11 (480 mg, 1.63 mmol, 1 equiv) in triethyl phosphite (10 mL) was stirred overnight at 90 °C. After cooling, hexane was added and the precipitate collected by vacuum filtration and purified by column chromatography (silica gel, 4:1 hexane/ethyl acetate) to afford the cross

• mmol, 2 equiv) and oxo compound (S,S)-16 (50 mg, 0.14 mmol, 1 equiv) in triethyl phosphite (2 mL) was stirred at 90 °C for 5 hours. After cooling hexane was added, the precipitate collected and purified by column chromatography (silica gel, hexane/ethyl actetate) to afford the enantiopure cross coupled

Ruthenium indenylidene “1^st generation” olefin metathesis catalysts containing triisopropyl phosphite

• Stefano Guidone,
• Fady Nahra,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2015, 11, 1520–1527, doi:10.3762/bjoc.11.166

• Stefano Guidone Fady Nahra Alexandra M. Z. Slawin Catherine S. J. Cazin EaStCHEM School of Chemistry, University of St Andrews, St Andrews, UK, KY16 9ST, UK 10.3762/bjoc.11.166 Abstract The reaction of triisopropyl phosphite with phosphine-based indenylidene pre-catalysts affords “1st generation

• -type ligands. Keywords: 1st generation; indenylidene; metathesis; phosphite; ruthenium; Introduction The olefin metathesis reaction is a powerful tool for C–C bond formation in the synthesis of highly valuable organic compounds [1][2][3][4]. Protocols involving W-, Mo- and Ru-based pre-catalysts can

• [10][11][12][13][24]. In order to reduce the cost of the Ru-based pre-catalyst, our group has investigated the use of phosphites as an economical alternative to phosphines. The reaction of triisopropyl phosphite with the pyridine-containing indenylidene complex [RuCl2(Ind)(SIMes)(py)] (SIMes = N,N

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

• Anna Kuźnik,
• Roman Mazurkiewicz,
• Mirosława Grymel,
• Katarzyna Zielińska,
• Jakub Adamek,
• Ewa Chmielewska,
• Marta Bochno and
• Sonia Kubica

Beilstein J. Org. Chem. 2015, 11, 1418–1424, doi:10.3762/bjoc.11.153

• orthoformate, diethyl phosphite and monoethyl methylphosphonite, followed by chromatographic separation of the three possible condensation products and the final hydrolysis, gave the expected phosphinylalkylphosphonic acid in only 17% yield [20]. The stepwise method consisted in the condensation of diethyl

• -picoline [20]. In 1989, Schrader and Steglich described an example of synthesis of diethyl 1-(N-acylamino)-1-[ethoxy(methylphosphinyl)]methylphosphonate using a Michaelis–Arbuzov-like condensation of the corresponding ethyl [1-(N-acylamino)-1-bromomethyl]methylphosphinate with triethyl phosphite in 79

• -(dimethylamino)methyl]dipropylphosphine oxide [(Pr)2POCH(NMe2)OEt] with diethyl phosphite in 74% yield [35]. In the present paper we report a novel method for α-phosphonylation, α-phosphinylation or α-phosphinoylation of 1-(N-acetylamino)alkylphosphonates that enables effective transformation of the starting

Thiazole-induced rigidification in substituted dithieno-tetrathiafulvalene: the effect of planarisation on charge transport properties

• Rupert G. D. Taylor,
• Joseph Cameron,
• Iain A. Wright,
• Neil Thomson,
• Olena Avramchenko,
• Alexander L. Kanibolotsky,
• Anto R. Inigo,
• Tell Tuttle and
• Peter J. Skabara

Beilstein J. Org. Chem. 2015, 11, 1148–1154, doi:10.3762/bjoc.11.129

• constructing a half-unit functionalised with a 1,3-dithiol-2-one, that can undergo a triethyl phosphite-mediated homocoupling to synthesise the central dithienoTTF in the final step. Herein, we present an alternative divergent route to dithienoTTFs, by utilising 4,6,4’,6’-tetrabromo-[2,2’]bis(thieno[3,4-d][1,3

• ]dithiolylidene) [15] as a core and appending heterocyclic arms through microwave assisted Stille couplings. It is worth noting that the tetrabromo-dithienoTTF core is still prepared via a triethyl phosphite-mediated homocoupling, but in this divergent route valuable heterocyclic groups can be introduced at the

• the synthesis of a half-unit and a final triethyl phosphite mediated homo-coupling. The resultant compounds, 1 and 2, were fully characterised and their optical and electrochemical properties elucidated via UV–vis spectroscopy and cyclic voltammetry, and explained in conjunction with DFT level

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• derivatives can be prepared from 6 and 7 by means of coupling reactions in triethyl phosphite (Scheme 3). The known homocoupling reaction of 6 affords the bis-tosylated BPTTF 5a in high yield with minimal purification [25]. We have obtained a comparable yield (76% vs 84%) working at twice the previously

Regioselective synthesis of chiral dimethyl-bis(ethylenedithio)tetrathiafulvalene sulfones

• Flavia Pop and
• Narcis Avarvari

Beilstein J. Org. Chem. 2015, 11, 1105–1111, doi:10.3762/bjoc.11.124

• -BEDT-TTF precursor. Compounds (S,S)-1 and (R,R)-1 were synthesized in two steps from the corresponding enantiopure dithiole-thiones (S,S)-5 and (R,R)-5 and the dithiolone-dithiopropionitrile 4 (Scheme 2). In the first step the phosphite-mediated heterocoupling between the two units provides the

A hybrid electron donor comprising cyclopentadithiophene and dithiafulvenyl for dye-sensitized solar cells

• Gleb Sorohhov,
• Chenyi Yi,
• Michael Grätzel,
• Silvio Decurtins and
• Shi-Xia Liu

Beilstein J. Org. Chem. 2015, 11, 1052–1059, doi:10.3762/bjoc.11.118

• (0.160 g, 0.5 mmol) in toluene (50 mL) was added dropwise into a hot solution of 3 (0.212, 0.5 mmol) and triethyl phosphite (10 mL) in toluene (50 mL) under nitrogen protection. The resulting mixture was stirred at reflux overnight. After removing the solvent under reduced pressure, the residue was

• (hexylthio)-1,3-dithiole-2-thione (0.090 g, 0.2 mmol) in toluene (50 mL) was added dropwise into a hot solution of 5 (0.101 g, 0.2 mmol) and triethyl phosphite (5 mL) in toluene (100 mL) under nitrogen protection. The resulting mixture was stirred at reflux overnight. After removing the solvent under reduced

Synthesis and characterization of the cyanobenzene-ethylenedithio-TTF donor

• Sandrina Oliveira,
• Dulce Belo,
• Isabel C. Santos,
• Sandra Rabaça and
• Manuel Almeida

Beilstein J. Org. Chem. 2015, 11, 951–956, doi:10.3762/bjoc.11.106

• -tetrathiafulvalene (CNB-EDT-TTF), was obtained in high yield, by a cross-coupling reaction with triethyl phosphite between 2-thioxobenzo[d][1,3]dithiole-5-carbonitrile and 5,6-dihydro-[1,3]dithiolo[4,5-b][1,4]dithiin-2-one. This new donor was characterized namely by single crystal X-ray diffraction, cyclic

• pure triethyl phosphite during 4 hours at 130 °C leading to the formation of 3 in relatively high yield (63%) (Scheme 1). This coupling reaction also gives rise to smaller amounts of BEDT-TTF (14% yield) and dicyanodibenzene tetrathiafulvalene (dcdb-TTF) [13] as byproducts resulting from homocoupling

• anisotropic thermal parameters whereas H-atoms were placed in idealised positions and allowed to refine riding on the parent C atom. Molecular graphics were prepared using MERCURY 1.4.2 [29]. General procedure for the synthesis of 3 In freshly destilled triethyl phosphite (10 mL), 2-thioxobenzo[d][1,3

Tuning of tetrathiafulvalene properties: versatile synthesis of N-arylated monopyrrolotetrathiafulvalenes via Ullmann-type coupling reactions

• Vladimir A. Azov,
• Diana Janott,
• Dirk Schlüter and
• Matthias Zeller

Beilstein J. Org. Chem. 2015, 11, 860–868, doi:10.3762/bjoc.11.96

• in hot triethyl or trimethyl phosphite. Using the second approach [17][18][19], the aryl group is attached to the MPTTF moiety using a direct copper-mediated Ullmann-type N-arylation reaction [20][21]; this method was also used for the preparation of arylated bis-pyrrolotetrathiafulvalenes 2

Trifluoromethyl-substituted tetrathiafulvalenes

• Olivier Jeannin,
• Frédéric Barrière and
• Marc Fourmigué

Beilstein J. Org. Chem. 2015, 11, 647–658, doi:10.3762/bjoc.11.73

• -withdrawing groups (EWG) is obtained by phosphite coupling involving CF3-substituted 1,3-dithiole-2-one derivatives. The relative effects of the EWG such as CF3, CO2Me and CN on the TTF core were investigated from a combination of structural, electrochemical, spectrochemical and theoretical investigations

• MeOH gives the corresponding primary amide 7 in 63% yield. Its dehydration with POCl3 in sulfolane gives 2ac in 60% yield. A similar phosphite-based cross-coupling reaction between the bis(trifluoromethyl)-1,3-dithiole-2-one derivative 9cc and the diester derivative 10bb gave the TTF 3bc in 15% yield

TTFs nonsymmetrically fused with alkylthiophenic moieties

• Rafaela A. L. Silva,
• Bruno J. C. Vieira,
• Marta M. Andrade,
• Isabel C. Santos,
• Sandra Rabaça,
• Dulce Belo and
• Manuel Almeida

Beilstein J. Org. Chem. 2015, 11, 628–637, doi:10.3762/bjoc.11.71

• analogous transition metals complexes, enabling their processing from solutions. Results and Discussion Synthesis The TTF donors fused non-symetrically with substituted thiophene moieties 1 and 2 were obtained by the cross coupling, in the presence of trimethyl phosphite, between compounds I and II and

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• -acylpyrroles [265] (Scheme 39). In their work, diethylzinc and 147 acts as a bifunctional catalyst system where the α,β-unsaturated system is activated through Lewis acid coordination and the catalyst acts as a directing group for the phosphite. Overall the reaction proceeds in both high yield and

Bis(vinylenedithio)tetrathiafulvalene analogues of BEDT-TTF

• Erdal Ertas,
• İlknur Demirtas and
• Turan Ozturk

Beilstein J. Org. Chem. 2015, 11, 403–415, doi:10.3762/bjoc.11.46

• phosphite at 130 °C for 3 h under a nitrogen atmosphere, which gave a mixture of cross coupled 43 and self coupled products 4a and 44. In order to remove the MEM protecting group, 43 was stirred in 20% HCl at room temperature for 2 days, which yielded the ET analogue 45, having two hydroxy groups. In 2000

• % yields. The fully unsaturated tetraphenyl analogue 52 of ET was obtained in 90% yield by a coupling reaction of 51, which was obtained by converting the thione group of 48 to its corresponding oxo form in 85% yield, in hot triethyl phosphite, yielding 52 in 90% yield (Scheme 7). A charge transfer salt 54

• coupling of 28 with 51 smoothly gave the corresponding ET analogue 56, its reaction with 57 did not produce any result (Scheme 9) [57]. This could be due to the reaction of the benzylphenyldithiole moiety with triethyl phosphite. Analogues of ET, having dithiin and thiophene rings along with hydroxy groups

A simple and efficient method for the preparation of 5-hydroxy-3-acyltetramic acids

• Johanna Trenner and
• Evgeny V. Prusov

Beilstein J. Org. Chem. 2015, 11, 323–327, doi:10.3762/bjoc.11.37

• turned to the alternative oxidation of enolates with molecular oxygen in the presence of triethyl phosphite as originally described by Hartwig [12][13][14][15]. Application of these conditions resulted in a clean conversion to the 5-hydroxy-3-acyltetramic acid but again, the isolated yield of the product

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• barrier was found to be high as no epimerization was detected up to 150 °C, and consistent with this, density functional theory calculations give an inversion barrier of over 40 kcal/mol. Keywords: acylphosphine; acyl phosphite; chiral; DFT; NMR; nucleic acids; oligonucleotides; Introduction Antisense

• interference has also been described [24]. We recently reported the synthesis of a number of chiral disulfide sulfurizing reagents [25] and the results of the sulfurization of phosphite triesters in order to look for stereoselectivity [26]. In order to change such a method into a practical synthesis route for

• several groups suggests that the inversion barrier is decreased to below 20 kcal/mol [28][29][30]. In order to extend the comparison from phosphines to phosphites, we recently showed that dinucleoside phosphite triesters, like phosphines, epimerize slowly – in this case at 150 °C with an inversion barrier

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• group for the enolization of the carbonyl function facilitating α-monochlorination under mild conditions. α-Chlorinated acylphosphonates can be easily cleaved by a nucleophile with the expulsion of phosphite. Therefore, the α-chloro acylphosphonates 10a–f were transformed to the corresponding

Superoxide chemistry revisited: synthesis of tetrachloro-substituted methylenenortricyclenes

• Basavaraj M. Budanur and
• Faiz Ahmed Khan

Beilstein J. Org. Chem. 2014, 10, 2531–2538, doi:10.3762/bjoc.10.264

• have not been studied systematically even though discovered more than half a century ago. Alkylpentachlorocyclopentadienes can be easily prepared from hexachlorocyclopentadiene by treatment with the corresponding phosphite esters by a known protocol [37]. 5-Alkylpentachlorocyclopentadienes were rarely

Solution phase synthesis of short oligoribonucleotides on a precipitative tetrapodal support

• Alejandro Gimenez Molina,
• Amit M. Jabgunde,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2014, 10, 2279–2285, doi:10.3762/bjoc.10.237

• synthetic cycle was composed of three steps, as usual: coupling, oxidation and deprotection. Couplings were carried out in a 1:1 mixture of MeCN and DMF under N2 using 1.5 equiv of the respective phosphoramidite building block per a support-bound 5'-hydroxy group. After coupling, the phosphite triester