Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies

• Giovanni Picca,
• Markus Probst,
• Simon M. Langenegger,
• Oleg Khorev,
• Peter Bütikofer,
• Anant K. Menon and
• Robert Häner

Beilstein J. Org. Chem. 2020, 16, 1732–1739, doi:10.3762/bjoc.16.145

• (DCM), and ETT served as the activator. The subsequent oxidation of the unstable phosphite triester to the more stable phosphotriester was performed with t-BuOOH. The resulting intermediates were then treated overnight with a solution of ammonia in methanol to remove the protecting groups. An overall

• -Dod-NBD was obtained in 10 steps, starting from citronellol and tert-butyldimethylsilyl (TBDMS)-protected dodecanediol [39]. The reaction of either of the alcohols with the sugar phosphoramidite using ETT led to phosphite intermediates 1a and 1b, respectively. The intermediates were then oxidized with

Synthesis and properties of tetrathiafulvalenes bearing 6-aryl-1,4-dithiafulvenes

• Aya Yoshimura,
• Hitoshi Kimura,
• Kohei Kagawa,
• Mayuka Yoshioka,
• Toshiki Itou,
• Dhananjayan Vasu,
• Takashi Shirahata,
• Hideki Yorimitsu and
• Yohji Misaki

Beilstein J. Org. Chem. 2020, 16, 974–981, doi:10.3762/bjoc.16.86

• ; one was the palladium-catalyzed C–H arylation of TTF with bromide 12 (Scheme 2a) and the other was the Vilsmeier–Haack reaction of 1a, followed by triethyl phosphite-mediated cross coupling with 11 (Scheme 2b). Theoretical calculations The DFT calculations of compounds 1a, 3a, and 4 have been carried

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• presence of a weak base [33]. After testing many modifications, it turned out that the use of triethylamine (1 equiv) as a base, and without a solvent, gave the best results with aldehydes 4 (1 equiv) and diethyl phosphite (1 equiv). These conditions not only increased the diastereoselectivity of the

• phosphite (1,0 equiv) and the appropriate aldehyde 4 (1,0 equiv). The reaction mixture was stirred at room temperature overnight, diluted with 20 mL of water and extracted with ethyl acetate (3 × 15 mL). The organic layers were washed with NaClsat., dried over MgSO4 or Na2SO4, filtrated and concentrated

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• ’-bisfenchyloxydichlorosilane (7), biphenyl-2,2’-bisfenchyloxychlorohydroxysilane (8) and biphenyl-2,2’-bisfenchyloxysilanediol (9) with precursor BIFOL (5) [52] and phosphite derivative BIFOP-Cl (6) [53]. Hydrolyses of dichlorosilane 7 and 14 to BIFOXSi(OH)2 (9, green circle) and bis(2,4,6-tri-tert-butylphenoxy)silanediol (15

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• reacted with diethyl phosphite or diphenylphosphine oxide using Pd(PPh3)4 as catalyst under microwave irradiation. The influence of the new compounds on the transport function of the organic anion transporting polypeptide OATP2B1 was investigated by measuring Cascade Blue uptake. Derivatives bearing a 3

• . Here we disclose the synthesis of novel 2- or 4-substituted 13α-estrone derivatives 8–13 via the Hirao reaction (Scheme 1). Diethyl phosphite (7a) or diphenylphosphine oxide (7b) were chosen as >P(O)H reagents and C–P couplings were planned under microwave irradiation using Pd-based catalysis

• , but the important benefits of microwave-irradiation have also been utilized in this field [29]. The optimization of reaction conditions was carried out using 2-bromo- or 2-iodo-13α-estrone 3-methyl ether (1 or 1I) as starting compounds and diethyl phosphite (7a) as the reagent (Table 1, Scheme 1). Two

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• synthetic advance is the phosphite-mediated heterocoupling of 1,3-dithiol-2-thiones F and 1,3-dithiol-2-ones G which provides efficient access to TTFs with two differently substituted 1,3-dithiol rings in an efficient way [49]. Simple heating of both monomers (ketone and thioketone) in P(OMe)3 or P(OEt)3

• breakthroughs for the construction of TTF-based supramolecular architectures: (b) Stepwise deprotection/alkylation, (c) phosphite-mediated heterocoupling, and (d) pyrrolo-annulated TTF derivatives I and J. (a) Host–guest equilibrium between π-electron-poor cyclophane 3 and different TTFs with their

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• performed using 118a–e as catalysts and isopropanol as a secondary alcohol hydride donor (Scheme 38). Although 99% ee was achieved with catalyst 118a in initial conversion stage, from the perspective of yield and enantioselectivity VANOL-derived phosphite catalyst 118d which has an extended π-delocalization

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• . After the desired number of such coupling-deprotection cycles, the phosphite-linked oligo-thymidine 16 was transformed in an oxidative amidation reaction [42] in the presence of iodine and N,N,N'-trimethylethylenediamine (17) to yield, after basic cleavage from the solid support, the envisioned

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• )diisopropylaminophosphoramidite with a partially-protected guanosine derivative to the corresponding phosphite triester was also effected (Scheme 12). Phosphate coupling using nucleoside phosphoromorpholidates is well established [51] but the reaction times are typically in the order of days. Recent developments in this field

• . Preparation of nucleoside phosphoramidites in a MBM using ionic liquid-stabilised chlorophosphoramidites (route A) or phosphorodiamidites (route B). Preparation of a nucleoside phosphite triester using LAG in a MBM. Internucleoside phosphate coupling linkages in a MBM. Preparation of ADPR analogues using in a

Electrochemical Corey–Winter reaction. Reduction of thiocarbonates in aqueous methanol media and application to the synthesis of a naturally occurring α-pyrone

• Ernesto Emmanuel López-López,
• José Alvano Pérez-Bautista,
• Fernando Sartillo-Piscil and
• Bernardo A. Frontana-Uribe

Beilstein J. Org. Chem. 2018, 14, 547–552, doi:10.3762/bjoc.14.41

• more environmentally friendly than the classical reaction, where a large excess of trialkyl phosphite as reducing agent and high temperatures are required. Thus, cathodic reduction at room temperature of two cyclic thiocarbonates (−1.2 to −1.4 V vs Ag/AgCl) afforded the corresponding alkenes, trans-6

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

• (DMTr) [26], tert-butyldimethylsilyl (TBDMS) [27][30], levulinoyl [26], or 2-azidomethylbenzoyl [27] (Figure 2), and applying either phosphotriester chemistry [28][29][31][32] or phosphite triester chemistry [25][26][27][30] in solution. In general, trinucleotides can be assembled through the reaction

• , although using phosphite triester chemistry [27]. In this case, the synthesis started with the coupling of an N-acyl-5'-O-DMTr-protected nucleoside-3'-O-phosphoramidite to an N-acyl-3'-O-TBDMS-protected nucleoside, followed by oxidation of the internucleotide phosphorous. Upon cleavage of the 5'-O-DMTr

• proceed by either phosphite triester chemistry or phosphotriester chemistry with the latter being the more robust method. Also H-phosphonate chemistry has been used for assembling short oligomers in solution [34], although not with the aim of generating trinucleotide synthons for gene synthesis. 2

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• -catalysed phosphitylation of the 4’-OH group with N,N-diethylaminophosphepane followed by oxidation of the intermediate phosphite with m-CPBA to furnish the corresponding phosphate, and subsequent deprotection of the 6’-O-TBDMS ether gave the hexaacylated phosphotriester 21. The glutaryl-glucose linker

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

• trifluoromethylsulfenylated analogue (Scheme 33). Yi and co-workers reported that the reaction could also be performed in acetonitrile at 90 °C, with diethyl phosphite as the reducing agent (Scheme 34) [43]. These modifications allowed to get improved yields for the trifluoromethylsulfenylation of indole and pyrrole

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• with diethyl phosphite in boiling 1,2-dichloroethane leading to the dialkyl dicyanosuccinates 96 [7]. Charge-transfer (CT) complexes Dialkyl dicyanofumarates E-1, similar to tetracyanoethylene (TCNE), are well-known as one-electron acceptors. They react with metallocenes 99, such as manganocenes [73

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

• are methyl, ethyl, isopropyl or, occasionally, n-butyl [127]. This observation is likely explained by the synthetic methods employed to prepare phosphonates that frequently made use of the Arbuzov reaction [128] involving the commercially available trimethyl, triethyl or triisopropyl phosphite [129

• reaction between di-tert-butyl phosphite and either benzyl halide [137] (Michaelis–Becker reaction) or aldehyde [134] (Pudovik reaction) or using tris-tert-butyl phosphite (Abramov reaction) [135]. The elimination of the t-Bu moieties can be efficiently achieved in presence of trifluoroacetic acid (TFA

• monohydrolysis can be also achieved using NaI as nucleophile in acetone [147] or butanone as solvent [148]. 3.2. Catalytic hydrogenolysis Dibenzyl phosphonates are readily synthesized using dibenzyl or tribenzyl phosphite. This type of phosphonate offers an alternative to the use of acidic conditions to prepare

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• thioglycosyl donor. The sulfide triflate 73 could activate the thioglycoside product, which provides a possible explanation for the modest yield. To avoid the side reaction caused by 73, triethyl phosphite was added as a scavenger to quench 73, which enhanced the glycosylation yield to 78%. The need for

• triethyl phosphite to prevent the undesired acceptor/product activation precludes the possibility of carrying out multiple glycosylation reactions in one pot using BSP/Tf2O. Other promoter systems such as NIS/TMSOTf, Ph2SO/Tf2O and BSM/Tf2O have similar complications due to the formation of thiophilic or

• ; then 96, and triethyl phosphite; (b) p-TolSCl/AgOTf, −60 °C; then 99. One-pot synthesis of Globo-H hexasaccharide 105 using building blocks 101, 102, 103 and 104. Synthesis of (a) oligosaccharides 109–113 towards (b) 30-mer galactan 115. Reagents and conditions: (a) TTBP, 4 Å MS, CH2Cl2, p-TolSCl

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

• that are the key motif of many natural products and pharmaceuticals. Consequently, new and straightforward methods to access indoles are highly desirable [35][36]. We chose a propargyl phosphite rearrangement to achieve allenyl intermediates and aimed to synthetize indoles via allenyl phosphonates

• , which were versatile synthetic intermediates [37][38]. The N-methyl-N-allylpropargyl alcohol 3 was treated with (EtO)2PCl under alkaline conditions, then underwent a propargyl phosphite/allenyl phosphonate rearrangement and an intramolecular nucleophilic attack to form the indole moiety, followed by

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• with acyl chlorides or chlorophosphates [11][12][13]. On applying the phosphoramidite chemistry, the phosphite triesters obtained are oxidized to phosphate triesters in each coupling cycle, whereas the H-phosphonate diesters may be stable enough to become oxidized only at the end of chain assembly

• , capping and oxidation (Scheme 4). The building blocks were base-moiety protected 5´-O-DMTr-nucleoside 3´-(2-cyanoethyl-N,N-diisopropylphosphoramidites), i.e., the ones used in standard solid-supported synthesis. Phosphite triesters were oxidized to phosphate triesters after each coupling with tert-butyl

• -dicyanoimidazole (DCI, 1.5 equiv) as an activator. The resulting phosphite triesters were converted to phosphate esters by conventional aq iodine oxidation. Precipitation by dilution with MeOH removed all traces of reagents and monomeric nucleoside derivatives. As a proof of concept, a pentamer, d(5´-AGCCT-3

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• the phosphite ligands (39b, 43). Interestingly, an ester group in the α-position increases the reactivity (43). The reaction works well with simple primary and secondary alkyl cyanides but requires a higher reaction temperature. Aliphatic nitriles containing β-hydrogen atoms are successfully reduced

The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

• Erika Bálint,
• Ádám Tajti,
• Anna Ádám,
• István Csontos,
• Konstantin Karaghiosoff,
• Mátyás Czugler,
• Péter Ábrányi-Balogh and
• György Keglevich

Beilstein J. Org. Chem. 2017, 13, 76–86, doi:10.3762/bjoc.13.10

• -aminophosphonate derivatives embrace the Kabachnik–Fields (phospha-Mannich) three-component condensation, where an amine, an aldehyde or ketone and a >P(O)H reagent, such as a dialkyl phosphite or a secondary phosphine oxide react in a one-pot manner [6][7][8][9][10], and the Pudovik (aza-Pudovik) reaction, in

• the dialkyl phosphite were applied [43][44][45][46][47][48][49][50][51][52]. The synthesis of α-aryl-α-aminophosphine oxides by the addition of secondary phosphine oxides to imines is much less studied. Only a few publications were found and the reported reactions were performed in solvent (in DEE

• (Table 1). The products were α-aminophosphonates 2a–d and α-aminophosphine oxide 2e. The addition of 1 equivalent of dimethyl phosphite (DMP) to imine 1a at 80 °C was almost complete after 30 min, and dimethyl ((butylamino)(phenyl)methyl)phosphonate (2a) could be isolated in a yield of 73% (Table 1

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• , followed by thermal Arbuzov rearrangement of the intermediate allyl phosphites (Scheme 1, reaction 1). Recently, an efficient protocol for the conversion of common allyl and benzyl alcohols into the corresponding phosphonates through their treatment with triethyl phosphite and ZnI2, was described [16

• ]. Similarly, Das and co-workers [17] have directly converted acyclic Morita–Baylis–Hillman (MBH) alcohols into the corresponding allylphosphonates upon their treatment with trialkyl phosphite in the presence of FeCl3 (Scheme 1, reaction 2). On the other hand, treatment of MBH acetates with triethyl phosphite

• , without any additive, provided, after thermal Arbuzov rearrangement, a variety of diethyl allylphosphonates (Scheme 1, reaction 3) [18]. Moreover, the asymmetric allylic substitution of MBH carbonates with diphenyl phosphonate using chiral thiourea phosphite as catalyst, afforded the related

Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

• Erika Bálint,
• Ádám Tajti,
• Anna Dzielak,
• Gerhard Hägele and
• György Keglevich

Beilstein J. Org. Chem. 2016, 12, 1493–1502, doi:10.3762/bjoc.12.146

• antibacterial, antiparasitic, anticancer and herbicidal activities [5]. (Aminomethylene)bisphosphonates may be prepared in different ways [5]. One of the most convenient and widespread methods is the three-component condensation involving an amine, an orthoformate and a dialkyl phosphite. Usually, primary or

• secondary amines were reacted with an equivalent, or a small excess of triethyl orthoformate and 2–7 equivalents of diethyl phosphite [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. In most cases, the corresponding acids were the target molecules that were obtained by hydrolysis of the esters

• step is the nucleophilic addition of diethyl phosphite to the C=N bond of the imines resulting in phosphonates III or IV, respectively. Then, the elimination of an amine or ethanol and the addition of another unit of diethyl phosphite may lead to (aminomethylene)bisphosphonates (VI). If the amine is in

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

• Souad Kachbi-Khelfallah,
• Maelle Monteil,
• Margery Cortes-Clerget,
• Evelyne Migianu-Griffoni,
• Jean-Luc Pirat,
• Olivier Gager,
• Julia Deschamp and
• Marc Lecouvey

Beilstein J. Org. Chem. 2016, 12, 1366–1371, doi:10.3762/bjoc.12.130

• is a procedure developed in our laboratory to introduce the bisphosphonate from acyl chloride and tris(trimethylsilyl)phosphite in one step. Keywords: bisphosphonate; Fe2O3 nanoparticle; polyethylene glycol derivatives; surface ligand synthesis; Introduction Numerous researchers are interested in

• functionalized substrates. In contrast, our lab has developed a new synthetic strategy starting from an acid chloride and tris(trimethylsilyl) phosphite, followed by a methanolysis step [15]. This one-pot procedure allows the synthesis of various aliphatic and aromatic bisphosphonic acids under mild conditions

• (trimethylsilyl) phosphite to the acyl chloride derivatives 8 and 9a,b yielded the corresponding silylated PEG-HMBP. The formation of silylated bisphosphonate was monitored by 31P NMR. After evaporation of volatile compounds under vacuum the silylated PEG-HMBP was hydrolyzed with methanol at room temperature for