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

• sodium borohydride and lithium bromide to 40 g scale, obtaining diol 11 with only a small reduction in yield (77% vs 85% at 15 g scale [33]). Compound 11 is then treated with phosphorus tribromide to afford dibromide 12. The scale up of this reaction to 36 g scale also results in a lower, but still

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

• addition reactions where they employed organocopper reagents and chiral phosphorus-based ligands [18]. This breakthrough in the field led to the development of different chiral ligands for asymmetric CA reactions. Another major advancement occurred in 1997 when Feringa’s group developed the first catalytic

Attempts to prepare an all-carbon indigoid system

• Şeref Yildizhan,
• Henning Hopf and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 363–372, doi:10.3762/bjoc.11.42

• ): representing the basic cross-conjugated π-electron system of the indigoid compounds [7][8][9]. Whereas the replacement of Y in 2 (X = O) by sulfur and selenium [10][11] or even tellurium [12][13] has been known for some time, derivatives of “phosphaindigo” (Y = various substituted phosphorus derivatives) have

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• large steric demand of encapsulating fenchane units renders the phosphorus atom nearly inaccessible by nucleophilic reagents, but only for BIFOP–Cl. In addition to the steric effect, a hypervalent P(III)–O interaction as well as an electronic conjugation effect causes the high reactivity of O–BIFOP–Cl

• , in Pd catalysts. Keywords: chirality; hydrolysis; phosphorus; rearrangements; terpenoids; Introduction Phosphorus halides are highly reactive intermediates for the synthesis of phosphites and phosphoramidites [1][2][3][4][5], which are widely used, for example, as ligands in catalysts [6][7][8][9

• analysis of the crystal structure of BIFOP–Cl (1) reveals the large steric demand of the fenchane units, which embed the phosphorus atom, thus making it inaccessible to nucleophilic reagents (Figure 4, Table 1) [14][15]. In contrast, the reduced protection of the phosphorus atom in O-BIFOP-Cl (3), which is

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

• corresponding acyl diamidites, RC(O)P(N(iPr)2)2 (R = Me (7), Ph (9)), without the intervention of sodium to give a phosphorus anion. The structure of 9 was confirmed by single-crystal X-ray diffraction. The coupling of the diamidites 7 and 9 with 5′-O-DMTr-thymidine was carried out with N-methylimidazolium

• (albeit not all) antisense reagents, including the two approved drugs, are phosphorothioates, in which one of the terminal oxygen atoms on the phosphodiester internucleotide linker is replaced by sulfur. A potential issue with phosphorothioates is the creation of a new stereocenter at every phosphorus

• P-chiral phosphorothioates, a trivalent dinucleoside phosphorus moiety is required that undergoes rapid epimerization under the sulfurization conditions – that is, the goal was to carry out a dynamic kinetic resolution with formation of a single epimeric phosphorothioate. In order to carry out the

Enhancing the reactivity of 1,2-diphospholes in cycloaddition reactions

• Almaz Zagidullin,
• Vasili Miluykov,
• Elena Oshchepkova,
• Artem Tufatullin,
• Olga Kataeva and
• Oleg Sinyashin

Beilstein J. Org. Chem. 2015, 11, 169–173, doi:10.3762/bjoc.11.17

• approaches have been employed to enhance the reactivity of 1-alkyl-1,2-diphospholes – the introduction of electron-withdrawing groups either at the phosphorus atoms or in the para-position of the arene ring. The alkylation of sodium 1,2-diphospha-3,4,5-triphenylcyclopentadienide with alkyl halides Hal-CH2-R

• : cycloaddition; phospholes; phosphorus heterocycles; polycyclic phosphines; retro-Diels–Alder reaction; Introduction Phospholes are weakly aromatic heterocycles and demonstrate rather different properties from those of their S, N and O counterparts [1][2]. Due to low their aromaticity, phospholes are of

• , phosphinidenes, etc. [2]. At the same time, the presence of electron-withdrawing substituents (cyano-, alkoxy-, or halo-) at the phosphorus atom reduces the aromaticity of the monophosphole ring and facilitates cycloaddition reactions resulting in novel 7-phosphanorbornenes [5][6], which was verified by

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• forward direction to synthesize optically active pharmaceuticals 9 and 10, we decided to prepare both enantiomers of corresponding bromide derivative 8. This was obtained by treatment of afore-prepared enantiopure alcohol (S)-(+)-5 with 1 equiv of phosphorus tribromide (PBr3) at room temperature carried

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• pyrolysis of the condensation product of benzaldehyde and aniline [6]. The reaction conditions were improved by Morgan and Walls, based on a reaction including a cyclization of phenanthridine by dehydrative ring-closure with phosphorus oxychloride in boiling nitrobenzene [7]. Over the 20th century this

Cyclodextrin-grafted polymers functionalized with phosphanes: a new tool for aqueous organometallic catalysis

• Jonathan Potier,
• Stéphane Menuel,
• David Mathiron,
• Véronique Bonnet,
• Frédéric Hapiot and
• Eric Monflier

Beilstein J. Org. Chem. 2014, 10, 2642–2648, doi:10.3762/bjoc.10.276

• signal due to the electro-withdrawing effect of both the sulfonate group and the phosphorus. Moreover, H4 was detected as a doublet due to the 3J scalar coupling with the phosphorus. H6 also appeared as a doublet (due to the coupling with H7) but its resonance was a little bit more shielded than H4 as H6

• did not benefit from the cumulative electron-withdrawing effects of both the sulfonate and the phosphorus. Contrary to H4, H6 showed cross-peaks with H7 and H8 whose doublets of doublets overlapped in the 1H spectrum and strongly correlated in the COSY spectrum. Once the sulfonated phosphine

• chemical environments of the phosphorus. The broadening of the 31P NMR signal was even more marked in D2O (Figure 2b). Several factors might be involved and be responsible for such disparity in phosphorus resonances. First, phosphanes could be included into CD cavities or not (“free” phosphanes). Moreover

Phosphinocyclodextrins as confining units for catalytic metal centres. Applications to carbon–carbon bond forming reactions

• Matthieu Jouffroy,
• Rafael Gramage-Doria,
• David Sémeril,
• Dominique Armspach,
• Dominique Matt,
• Werner Oberhauser and
• Loïc Toupet

Beilstein J. Org. Chem. 2014, 10, 2388–2405, doi:10.3762/bjoc.10.249

• cavity-shaped ligands, HUGPHOS-1 and HUGPHOS-2, to generate exclusively singly phosphorus-ligated complexes, in which the cyclodextrin cavity tightly wraps around the metal centre, was explored with a number of late transition metal cations. Both cyclodextrin-derived ligands were assessed in palladium

• , Buchwald and Hartwig on the use of monophosphine ligands in cross-coupling reactions, notably carbon–carbon ones such as the Mizoroki–Heck [1][2][3] and Suzuki–Miyaura reactions [4][5][6], there is a renewed interest for tertiary phosphines that favour the formation of singly phosphorus-ligated complexes

• to prevent the coordination of a second phosphorus atom [13][14] or cavity-shaped phosphines [15]. The use of sterically-hindered P(III)-derivatives, notably phosphites [16][17][18][19][20][21], has also proven beneficial in yet another carbon–carbon forming reaction, namely the rhodium-catalysed

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• . Nitrogen-, phosphorus-, oxygen-, and sulfur-substituted olefins and allenamides were compatible with these B4-catalyzed reactions. Fu’s results provided useful hints for further expansion of the substrate scope. Using B2 as the chiral catalyst, Marinetti and co-workers also developed several asymmetric [3

Organophosphorus chemistry

• Paul R. Hanson

Beilstein J. Org. Chem. 2014, 10, 2087–2088, doi:10.3762/bjoc.10.217

• heights. This Thematic Series highlights and details some of the novel methods that are advancing the field of organophosphorus chemistry. The Thematic Series covers topics that range from new synthetic methods and phosphorus-based ligands in asymmetric catalysis to bisphosphonates as promising enzyme

• phosphinoyl-indoles and phosphinoyl-isocoumarins and new chemistries of H-phosphonates. The Thematic Series also details work on new metathesis-based reactions of vinyl phosphonates and phosphate tethers, novel phosphorus-based ligands in asymmetric catalysis, novel rasta resin–triphenylphosphine oxides and

P(O)R₂-directed Pd-catalyzed C–H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands

• Rong-Bin Hu,
• Hong-Li Wang,
• Hong-Yu Zhang,
• Heng Zhang,
• Yan-Na Ma and
• Shang-dong Yang

Beilstein J. Org. Chem. 2014, 10, 2071–2076, doi:10.3762/bjoc.10.215

• . China 10.3762/bjoc.10.215 Abstract Chiral phosphorus ligands have been widely used in transition metal-catalyzed asymmetric reactions. Herein, we report a new synthesis approach of chiral biaryls containing a phosphorus moiety using P(O)R2-directed Pd-catalyzed C–H activation; the functionalized

• products are produced with good enantioselectivity. Keywords: chiral synthesis; Pd-catalysis; organophosphorus; phosphorus ligands; P(O)R2-directing; Introduction In the past decades, phosphorus ligands have been demonstrated to be efficient ligands in many metal-catalyzed organic reactions [1][2][3][4

• ]. In particular, their special effects of enhancing the metal-catalyst efficiency and of controlling chiral induction has continually prompted synthetic chemists to probe efficient methods generating access to chiral, enantiomerically pure phosphorus compounds used in pharmaceutical, agrochemical and

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• constant on the dihedral angle according to the well-known Karplus relationship, one would expect the 3J(C,P) of the carbon in the trans arrangement to the phosphorus atom to evince larger splitting than the other arranged in the cis arrangement. Thus, 3J(C2’,P) > 3J(C5’,P) in rotamer A and 3J(C5’,P) > 3J

Relay cross metathesis reactions of vinylphosphonates

• Raj K. Malla,
• Jeremy N. Ridenour and
• Christopher D. Spilling

Beilstein J. Org. Chem. 2014, 10, 1933–1941, doi:10.3762/bjoc.10.201

• phosphorus; relay; vinyl phosphonate; Introduction Over the last two decades, we have developed reactions for the formation of chiral non-racemic γ-substituted vinylphosphonates [1][2][3][4][5][6][7][8][9]. In particular, carbonate derivatives 1 (phosphono allylic carbonates) of allylic hydroxy phosphonates

• chromatography resulted in some loss of material leading to an isolated yield of 45%. In addition, the 31P NMR spectrum of the crude reaction mixture indicated the formation of a new phosphorus-containing product with a signal at 43 ppm, consistent with formation of the oxaphosphole 22 [25]. An impure sample of

• of vinylphosphonate 21a with styrenes. The dimeric product 27 was not observed during the cross metathesis of the vinylphosphonate 21a with methyl acrylate. Diallyl vinylphosphonates (28) are reported to undergo ring closing metathesis to give either 7-membered (29) or 5-membered (30) phosphorus

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• previously described the use of (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) for the dehydration of aldoximes to cyanides [22]. In that work, analysis of the reaction course by 31P{1H} NMR did not show the formation of a new phosphorus signal other than that for HMPA, which

• decided to investigate other reactive BtOH derivatives for this reaction. A variety of phosphorus and sulfonate derivatives of BtOH has been synthesized and studied as peptide-coupling agents [30]. Amongst these we selected the easily synthesized tosylates of BtOH (Bt-OTs) and its 7-aza analogue AtOH (At

• mechanisms were proposed, namely reaction of the carboxylate at the phosphorus center (equivalent to pathway a in Scheme 3) or a SN2’ reaction at the N3 atom (equivalent to pathway b in Scheme 3) [34]. Experiments with [18O]-labeled benzoate indicated that conversion of carboxylic acids to the acyl HOBt

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• enolization. Thus, treatment of Δ5-cholestenone with 24a yielded the unconjugated olefin 27a in addition to recovered unreacted enone, whereas phosphorus ylides would form Δ4-cholestenone via enolization and double bond conjugation [20]. Other monocyclic phosphonamides with application in olefination

• phosphorus center, whereas cis confers to a R-configuration. Degradation of the adducts by ozonolysis yielded oxocycloalkane-3-carboxaldehydes 43, which are useful synthetic intermediates. Diastereomer cis-40b however gave only poor diastereofacial selection, providing the corresponding 1,4-addition adducts

• dichlorides can be obtained either from chlorination of phosphonic acids [65][66] or from treatment of an allyl chloride such as 61 with phosphorus trichloride followed by hydrolysis to give 62 [15][67]. Reactions of unsymmetrical amines or aminoalcohols such as ephedrine with phosphonic acid dichlorides

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• atoms (C-5OH···FC-2 1.98 Å). The other structure (C-3-exo conformer; ET = −732310.1 kcal/mol) does not contain the intramolecular hydrogen bonds. The torsion angles of the vicinal hydrogen atoms H-1/H-2 and H-2/H-3, the hydrogen–fluorine (H-1/F and H-3/F) and hydrogen–phosphorus (H-1/P), and the carbon

• –fluorine (C-4/F) and carbon–phosphorus (C-2/P) atoms are in satisfactory agreement with the experimental coupling constants. On the other hand, the vicinal torsion H-3/H-4 angles (79° and 91°) are not in accordance with the relevant coupling constant (5.40 Hz). However, the H-3/H-4 torsion angle (162°) of

Synthesis of new, highly luminescent bis(2,2’-bithiophen-5-yl) substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole

• Anastasia S. Kostyuchenko,
• Vyacheslav L.Yurpalov,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2014, 10, 1596–1602, doi:10.3762/bjoc.10.165

• with phosphorus oxychloride, in 78 and 83% yields, respectively. The reaction of 11 with a Lawesson’s reagent led to the formation of 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-tiadiazole (15, 70% yield) (Scheme 4). To the contrary, 3,5-bis(3-decyl-2,2'-bithiophen-5-yl)-4-phenyl-4H-1,2,4-triazole (18

• -N-phenyl-2,2'-bithiophene-5-carboximidoyl chloride (17) by the reaction with phosphorus pentachloride, and then, without additional purification, used at once in the reaction with acyl hydrazide 10. As a result, 3,5-bis(3-decyl-2,2'-bithiophen-5-yl)-4-phenyl-4H-1,2,4-triazole (18) was obtained in 62

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• , possessing a diphenylphosphanyl group and ligand L3 derived from tert-leucinol (Figure 3). Not surprisingly, installation of the less hindered phosphorus moiety in L2 negatively affected the asymmetric induction: the corresponding product 3a was obtained in only 78–79% ee (Table 2, entries 3 and 4). However

• assessed the possibility of conformational equilibrium for the six-membered arylpalladium species bearing L1 (Scheme 4). The non-planar six-membered palladacycle [66][67][68][69] can potentially adopt one of two conformations: I1, in which the syn-tert-butyl substituent at phosphorus assumes a pseudo

• thermodynamically disfavored compared to I1. This hypothesis was also supported by a single crystal X-ray analysis of (L1)PdCl2 complex (Figure 4). The resolved crystal structure clearly shows that the syn-(C14) and anti-substituent (C18) at phosphorus adopt a pseudo-equatorial and a pseudo-axial position

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• these compounds is attributed to the interaction of the electronic states of the compounds with significant contribution from the phosphorus atom with the phosphate backbone of DNA from just sitting on the grooves. The cleavage of supercoiled plasmid by the TPAs (5 and 6) indicates possible formation of

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

• Zeng-Wei Lai,
• Rong-Fei Yang,
• Ke-Yin Ye,
• Hongbin Sun and
• Shu-Li You

Beilstein J. Org. Chem. 2014, 10, 1261–1266, doi:10.3762/bjoc.10.126

• an elegant synthesis of bis(perfluoroalkyl)phosphine-oxazoline ligands where small but strongly electron-withdrawing substituents were introduced at the phosphorus [34]. 1,2-Ferrocene based P,N-ligands were synthesized and gave excellent regio- and enantioselectivities in the Pd-catalyzed allylic

• the R group has the ability to stabilize the carbocation, the electronic factor would favor the formation of the branched product (path b). The phosphorus atom has a stronger trans effect comparing with the oxazoline nitrogen, indicating that the carbon trans to phosphorus atom bears more

• electropositivity [46]. This fact may be responsible for the preferred placement of the substituted allylic carbon in the trans position to the phosphorus atom to better stabilize the electropositivity of the carbon. When the nucleophile attacks the more electropositive substituted allylic carbon terminus, a

Synthesis of ethoxy dibenzooxaphosphorin oxides through palladium-catalyzed C(sp²)–H activation/C–O formation

• Seohyun Shin,
• Dongjin Kang,
• Woo Hyung Jeon and
• Phil Ho Lee

Beilstein J. Org. Chem. 2014, 10, 1220–1227, doi:10.3762/bjoc.10.120

• We report an efficient Pd-catalyzed C(sp2)–H activation/C–O bond formation for the synthesis of ethoxy dibenzooxaphosphorin oxides from 2-(aryl)arylphosphonic acid monoethyl esters under aerobic conditions. Keywords: C–H activation; catalysis; cyclization; palladium; phosphorus heterocyclic compound

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• design of phosphorus-based amphiphilic compounds. 2. Mechanism of the Atherton–Todd reaction In their initial publication, Atherton and Todd have suggested two possible mechanisms to explain the formation of phosphoramidate [1]. The first one (Scheme 2-i) was based on a two-step sequence with the

• by the existence of some similitude with the reactivity of carbon tetrachloride reported in literature (e.g., the synthesis of arylcarboxylate according to a Reimer–Tiemann reaction [3][4]) and because the second step (i.e., the nucleophilic substitution on the electrophilic phosphorus) shares some

• in favor of the addition of the nucleophilic amine on chlorophosphorinane as intermediate. All the studies reported above shed some light on the mechanism of the AT reaction. None of these studies, however, focused on the chirality at the phosphorus atom. The first investigation of the

Novel indolin-2-one-substituted methanofullerenes bearing long n-alkyl chains: synthesis and application in bulk-heterojunction solar cells

• Irina P. Romanova,
• Andrei V. Bogdanov,
• Inessa A. Izdelieva,
• Vasily A. Trukhanov,
• Gulnara R. Shaikhutdinova,
• Dmitry G. Yakhvarov,
• Shamil K. Latypov,
• Vladimir F. Mironov,
• Vladimir A. Dyakov,
• Ilya V. Golovnin,
• Dmitry Yu. Paraschuk and
• Oleg G. Sinyashin

Beilstein J. Org. Chem. 2014, 10, 1121–1128, doi:10.3762/bjoc.10.111

• crystalline domains. Moreover, the more soluble AIMs do not show a better miscibility with the P3HT crystalline phase. Keywords: bulk heterojunction; fullerenes; isatin; phosphorus; photovoltaics; Introduction Organic photovoltaics are a rapidly growing field of research due to its potential for production