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

• nucleic acid polymerizations described so far have utilized activated starting materials, such as cyclic phosphates [1][2] or phosphoroimidazolides [3][4]. The trivalent phosphorus atom of phosphorous acid is much more susceptible to a nucleophilic attack than the pentavalent phosphorus atom of phosphoric

• 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

• 1955 [7]. Since then, both terrestrial [8] and extraterrestrial [9] sources of reduced phosphorus have been identified. Recent studies suggest the presence of significant amounts of phosphite in the Archean ocean, lending support to the idea of prebiotic phosphite chemistry [10][11]. Monoesters of

Aluminacyclopentanes in the synthesis of 3-substituted phospholanes and α,ω-bisphospholanes

• Vladimir A. D’yakonov,
• Alevtina L. Makhamatkhanova,
• Rina A. Agliullina,
• Leisan K. Dilmukhametova,
• Tat’yana V. Tyumkina and
• Usein M. Dzhemilev

Beilstein J. Org. Chem. 2016, 12, 406–412, doi:10.3762/bjoc.12.43

• efficient one-pot process for the synthesis of 3-substituted phospholanes and α,ω-bisphospholanes was developed. The method involves the replacement of aluminium in aluminacyclopentanes, prepared in situ by catalytic cycloalumination of α-olefins and α,ω-diolefins, by phosphorus atoms on treatment with

• organophosphorus compounds (OPC) is the direct transformation of five-membered metallacarbocycles based on transition metals to phosphacarbocycles on treatment with phosphorus dihalides. For example, a method for the direct conversion of zirconacyclopentenes [1][2][3][4] and zirconacyclopentadienes [5] to

• substituted phospholenes [6] and phospholes [7] has been reported. This approach was used to obtain materials for light-emitting diodes (LEDs) [8], phosphorus-containing polymers [9][10], bisphospholes [11], bicyclodiphospholanes and spirobicyclodiphospholanes [12][13]. However, this method is faced with some

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• organophosphorus (NOPs) share a typical structure with a pentavalent phosphorus atom linked to a leaving group (LG), two substituents (R1 and R2) and an oxygen or a sulfur atom (Figure 1), explaining the wide structural diversity of organophosphates. They can be classified into three categories depending on the

• radius whereas the β- and γ-CDs’ primary alcohols cones are similar. The guest molecule’s inclusion depth corresponds to the distance from the phosphorus atom to the secondary OH rim. As this distance is the highest with γ-CD, diazinon (5, Figure 3) is more deeply inserted [47]. According to these

• in the mode of inclusion. For instance, aromatic ring as substituent of the phosphorus atom are often included into the cavity, while steric hindrance is able to impair the complex formation. Finally, without aromatic groups, the mode of entry of the pesticide depends on the specific affinity of the

A concise and efficient synthesis of benzimidazo[1,2-c]quinazolines through CuI-catalyzed intramolecular N-arylations

• Xinlong Pang,
• Chao Chen,
• Ming Li and
• Chanjuan Xi

Beilstein J. Org. Chem. 2015, 11, 2365–2369, doi:10.3762/bjoc.11.258

• Xinlong Pang Chao Chen Ming Li Chanjuan Xi Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China, Tel: +86-10-62773684 College of Chemistry and Molecular Engineering, Qingdao University of

Life lessons

• Jonathan R. Nitschke

Beilstein J. Org. Chem. 2015, 11, 2350–2354, doi:10.3762/bjoc.11.256

• space, going from a one-dimensional linear array (Figure 1a) [7] to a two-dimensional grid (Figure 1b) [8] to a three-dimensional tetrahedron (Figure 1c) [9], which turned out to be capable of binding white phosphorus (P4) and rendering it air-stable [10]! The work went well at Geneva – we were

Two strategies for the synthesis of the biologically important ATP analogue ApppI, at a multi-milligram scale

• Janne Weisell,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2015, 11, 2189–2193, doi:10.3762/bjoc.11.237

• vacuo. The product 4 (822 mg, 23%) was present as a colorless oil. All NMR data were comparable to those reported elsewhere (except –OCH3 signals which was wrongly interpreted to be two singlets although those protons are coupled to phosphorus) [12]. 1H NMR (CDCl3) 4.84 (s, 1H), 4.77 (s, 1H), 4.16 (vq

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

• phosphines [14][15][16][17][18][19][20][21][22][23]. The most common phosphine, so called “throw-away ligand”, is tricyclohexyl phosphine [10][11][12][13][14][15][16][17][18][19][20][21][22][23]. In other words, such phosphorus donor ligands dissociate from the metal center to afford the 14e− active species

• with a cis-disposition of the phosphorus donor ligands. This geometry was confirmed by X-ray diffraction analysis on a single crystal (Figure 2). Synthesis of [RuCl2(Ind){P(OiPr)3}2] (2) The synthesis of the bis-phosphite species 2 was first attempted by the reaction of Ind-I with 2.5 equivalents of P

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• compounds and their structural analogues. Results and Discussion The synthetic pathway is presented in Scheme 1. The reaction of 2-benzylaniline (3) with N-phthalylglycyl chloride (4) gave amide 5 in 87% yield. The Bischler–Napieralski condensation of amide 5 using phosphorus oxychloride in acetonitrile led

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

• acid phosphorus analogues; electrochemical α-methoxylation; 1-phosphinoylalkylphosphonate; 1-phosphinylalkylphosphonate; Introduction α-Aminophosphonic and α-aminophosphinic acids, as phosphorus analogues and bioisosters of α-amino acids, exhibit a variety of important biological properties [1][2][3

• derivatives consist in the consecutive formation of two Cα–P bonds between a carbon electrophile (most often an electrophilic imine intermediate) and two identical molecules of the proper phosphorus nucleophile. Another group of methods requires the formation of a Cα–N bond between an easily accessible

• at low temperature (Scheme 2). The most characteristic feature of the 13C NMR spectra of these compounds was a doublet of doublets in the range of 45–58 ppm (J1 = 42–49 Hz, J2 = 151–160 Hz) assigned to the α-carbon atom coupled with two nonequivalent phosphorus atoms as well as the presence of two

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• may possess further functionalities in addition to the phosphorus center such as the γ-hydroxypropyl group which results from the ring opening and π-donor moieties such as aryl, allyl, propargyl and allene which originates from the Grignard reagent. Keywords: chirogenic phosphorus; Grignard reagents

• ; oxaphospholanes; phosphinates; phosphine oxides; Introduction Organophosphorus compounds containing phosphorus to carbon bond(s) are widely used in organic transformations. Textbook examples are the Wittig and the Horner–Wadsworth–Emmons reactions. Moreover, the vast majority of ligands used in organometallic

• : (A) Attack by nucleophilic low valent phosphorus compounds (P(III) or phosphide ions P(II)) on positively charged carbon centers (e.g., Michaelis–Arbuzov [7], Michaelis–Becker [8], Pudovik [9], Friedel–Crafts reactions [10], catalytic hydrophosphorylation [11] and others). Notably, these reactions

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

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