Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

• Yongguang Wang,
• Ruiyang Bao,
• Shengdian Huang and
• Yefeng Tang

Beilstein J. Org. Chem. 2013, 9, 1601–1606, doi:10.3762/bjoc.9.182

• strategy was designed as a fallback, in which katsumadain A could be accessed from the lactol 5a and phosphonate 6 via a tandem Horner–Wadsworth–Emmons (HWE)/oxa-Michael addition reaction [16]. In turn, 5a could be derived from 3 and cinnamaldehyde (7) by an organocatalytic enantioselective 1,4-conjugate

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• representative synthesis of stilbene 46a is shown (Scheme 4B). Initial Wadsworth–Emmons reaction between diethyl (4-nitrobenzyl)phosphonate (47) and 4-methoxybenzaldehyde (48) constructed the stilbene core 49. The target compound 46 was formed from a straightforward sequence of nitro reduction, reductive

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• three phosphonate (PO3H2) groups at the bridged carbon atom. Like well-known methylenebisphosphonates (BPs), they are characterized by a P–C–P backbone structure and are chemically stable mimetics of the endogenous metabolites, i.e., inorganic pyrophosphates (PPi). Because of its analogy to PPi and an

• chemistry are based on their specific properties. The presence of three phosphonate (PO3R2) substituents at the bridged carbon atom causes pronounced physical and chemical effects and imparts unique electronic characteristics to 1,1,1-trisphosphonylated compounds. Most importantly, the replacement of the

• hydrogen atom attached to the bridge carbon in methylenebisphosphonates by a third ionisable phosphonate moiety results in supercharged isosteric systems relative to pyrophosphoric acid [7]. It was also demonstrated that steric effects play a significant role in trisphosphonate chemistry and allow

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• the ready formation of bicyclic compound 72 [33]. The use of a phosphonate-containing alkene allows the assembly of numerous polycyclic structures by combining the radical addition of a ketone-bearing xanthate with an intramolecular Horner–Wadsworth–Emmons condensation. This strategy is highlighted in

• Scheme 15 by the synthesis of bicyclic cyclobutane derivatives 74 and 75 starting from 2-xanthyl cyclobutanone 73 [35]. Thus, depending on the distance between the terminal alkene and the phosphonate, a six- or a seven-membered ring may be fused onto the cyclobutane nucleus. This combination represents

• in fact a highly flexible route to polycyclic derivatives, since it is open to numerous variations. For instance, instead of having the phosphonate group attached to the alkene, it can be part of the xanthate component. Such a modification can be used to build the CD ring system found in the highly

Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• obtained through the addition of Davies amine, furnishing 8. Hydrogenation of compound 8 followed by N-protection as a carbamate would furnish the β-amino ester precursor of the phosphonate 13. In route B, the most convergent, the preparation of the phosphonate was envisaged in the first step; then

• , hydrogenation would furnish amino phosphonate. In method A the last step to synthesize 13 would be a nucleophilic addition of diethyl methylphosphonate under basic conditions, whereas for method B, the final step would be the N-protection of the amino phosphonate as a carbamate. The two routes were then tested

• our model substrate. Those conditions were then applied to a wide range of functionalized aldehydes with phosphonate 13a–g, giving amino ketone 15a–z in good to excellent yields and high E/Z ratio (≥ 95%). The results are presented in Table 3. Conclusion In summary, a general methodology has been

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• Pechmann condensation [11] from ethyl 4-chloroacetoacetate and resorcinol or its 6-halogenated derivatives (3a, 77.4% yield; 3b, 78.0%; 3c, 70.0%). By suspending compound 3 in triethyl phosphate with a catalytic amount of sodium iodide and heating the mixture under reflux, phosphonate 4 was prepared and

• at all when KOt-Bu was used. This indicates that KOt-Bu is not basic enough to deprotonate the α-hydrogen of phosphonate 4 at 25 °C. However, when the reaction temperature was raised to 55 °C, the deprotonation happened and compound 5 was afforded with good yield (Table 2). This indicates that the

An improved synthesis of a fluorophosphonate–polyethylene glycol–biotin probe and its use against competitive substrates

• Hao Xu,
• Hairat Sabit,
• Gordon L. Amidon and
• H. D. Hollis Showalter

Beilstein J. Org. Chem. 2013, 9, 89–96, doi:10.3762/bjoc.9.12

• combined 90% yield. The phosphonate moiety was installed under standard Arbuzov conditions by heating 4b under reflux in neat triethyl phosphite for 1 h to provide novel intermediate 5 in 92% yield following purification by column chromatography. Clean removal of the benzyl protecting group under standard

• conditions of catalytic hydrogenolysis provided, in 96% yield, the known phosphonate polyether alcohol 6, the synthesis of which had been accomplished previously by a different route [17]. Activation of the alcohol moiety of 6 to the succinimidyl carbonate 7 was carried out under standard conditions in 87

• stage was now set for a two-step modification of the phosphonate moiety. Reaction of 8 with lithium azide in hot DMF, under conditions developed for the monodealkylation of phosphonic acid dialkyl esters of nucleosides [19], provided the novel monoethyl ester 9 in 87% yield following purification by a

Highly selective synthesis of (E)-alkenyl-(pentafluorosulfanyl)benzenes through Horner–Wadsworth–Emmons reaction

• George Iakobson and
• Petr Beier

Beilstein J. Org. Chem. 2012, 8, 1185–1190, doi:10.3762/bjoc.8.131

• successful attempts have been made to favor Z-alkenes [26][27][28]. Results and Discussion The HWE reaction of phosphonate 3 with benzaldehyde in the presence of a base giving stilbene derivative 5a was investigated. At first, attempts were made to form 5a directly from 1 and diethyl chloromethylphosphonate

• isolated phosphonate 3. We found that various bases mediate the HWE reaction. t-BuOK in THF gave good results; however, the reaction required heating to 50 °C for at least one hour. With n-BuLi the reaction is complete at ambient temperature in about half an hour. By using an extended reaction time, much

• various aldehydes with phosphonate 3 was explored (Table 2). Aromatic aldehydes with electron-donating groups required longer reaction times than those with electron-acceptor groups. All tested aromatic aldehydes provided compounds 5 in high isolated yields and selectivities. Application of (E

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• L19 and L20 but also the N,O-chelating phosphonate ligand L21 showed a significant catalytic activity. From the group of diimine ligands, L28 [30] gave the best results. It should be noted that also in this class, structurally related ligands showed drastically different catalytic activities in the

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• GFcomplex to be more stable than that of cyclohexanol. However, it indicates that complexation of only part of the total substrate amount could ensure efficient conversion, if the oxime group of the cyclodextrin can approach the phosphonate moiety of the substrate in the complex, and if complexation

Lithium phosphonate umpolung catalysts: Do fluoro substituents increase the catalytic activity?

• Anca Gliga,
• Bernd Goldfuss and
• Jörg M. Neudörfl

Beilstein J. Org. Chem. 2011, 7, 1189–1197, doi:10.3762/bjoc.7.138

• Anca Gliga Bernd Goldfuss Jorg M. Neudorfl Department für Chemie, Universität zu Köln, Greinstr. 4, D-50939 Köln, Germany 10.3762/bjoc.7.138 Abstract Fluorinated and nonfluorinated phosphonates are employed as precatalysts in lithium phosphonate catalyzed cross benzoin couplings. Surprisingly, a

• comparable activities for lithium phosphonate and cyanide [19][20]. Recently, we introduced fenchol based phosphonates as precatalysts, which are similarly accessible as fencholate metal catalysts [21][22][23][24][25], in the benzoin coupling (Scheme 2) [26]. A strong increase of the catalytic activity was

• bonding orbitals, which leads to an increased s-character in the bonding P–H orbital. The smallest influence on the coupling constant is apparent for phosphonate 11, in which the fluoro substituents are not in close proximity to the phosphorous atom (five bonds distance). The largest 1J(P–H) coupling

Synthesis of 5-(2-methoxy-1-naphthyl)- and 5-[2-(methoxymethyl)-1-naphthyl]-11H-benzo[b]fluorene as 2,2'-disubstituted 1,1'-binaphthyls via benzannulated enyne–allenes

• Yu-Hsuan Wang,
• Joshua F. Bailey,
• Jeffrey L. Petersen and
• Kung K. Wang

Beilstein J. Org. Chem. 2011, 7, 496–502, doi:10.3762/bjoc.7.58

• with iodine [7]. 1-Ethynyl-2-iodo-benzene (15) [30] was prepared in quantitative yield by desilylation of 1-iodo-2-[2-(trimethylsilyl)ethynyl]benzene with sodium hydroxide in methanol. 1-Ethynyl-2-(methoxymethyl)benzene (4b) [31] and dimethyl (1-diazo-2-oxopropyl)phosphonate [32] were prepared

Regioselective ester cleavage during the preparation of bisphosphonate methacrylate monomers

• Kamel Chougrani,
• Gilles Niel,
• Bernard Boutevin and
• Ghislain David

Beilstein J. Org. Chem. 2011, 7, 364–368, doi:10.3762/bjoc.7.46

• (meth)acrylates, and can be readily polymerized by emulsion or solution methods [8][9]. Polymers with some phosphonate functionality have long been established as excellent adhesives and anti-corrosion compounds [10][11][12][13][14][15][16][17], however, there has been very little investigation into the

• use of phosphonate-type methacrylates for the same purpose [8][9]. In the domain of polymer-based materials exhibiting specific properties, bifunctional monomers bearing a methacrylate function and a bisphosphonate function are recognized as useful building blocks for dental materials [11][12][18][19

• phosphonate deprotection by TMSBr involved the presence of a tertiary amine but the authors did not mention any cleavage of the carboxylic ester to prove the role of the base used during the selective deprotection of the phosphonic ester into its acid [32]. We finally deprotected the trimethylsilyl

Effects of anion complexation on the photoreactivity of bisureido- and bisthioureido-substituted dibenzobarrelene derivatives

• Heiko Ihmels and
• Jia Luo

Beilstein J. Org. Chem. 2011, 7, 278–289, doi:10.3762/bjoc.7.37

• with chiral mandelate, camphorsulfonate and binaphthyl phosphonate in a variety of solvents including acetone, acetonitrile, ethyl acetate, dichloromethane, and benzene. Although the DPM rearrangement of the dibenzobarrelene 1i took place readily upon irradiation and the semibullvalene photoproducts

Miniemulsion polymerization as a versatile tool for the synthesis of functionalized polymers

• Daniel Crespy and
• Katharina Landfester

Beilstein J. Org. Chem. 2010, 6, 1132–1148, doi:10.3762/bjoc.6.130

• nucleation. On the other hand, latexes with MMA and 10 wt % vinylphosphonic acid showed the highest density of phosphonate functionality (0.66 group/nm²) at pH = 10. Lu et al. introduced the term “emulsifier-free miniemulsion polymerization” for the copolymerization of styrene and sodium p-styrene sulfonate

α,β-Aziridinylphosphonates by lithium amide-induced phosphonyl migration from nitrogen to carbon in terminal aziridines

• David. M. Hodgson and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2010, 6, 978–983, doi:10.3762/bjoc.6.110

• David. M. Hodgson Zhaoqing Xu Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK, Fax: +44(1865) 285002 10.3762/bjoc.6.110 Abstract N-Phosphonate terminal aziridines undergo lithium 2,2,6,6-tetramethylpiperidide-induced N- to C-[1,2

• our investigations [9][10][11][12][13] on the generation and subsequent chemistry of α-lithiated terminal aziridines [14], we considered whether α,β-aziridinylphosphonates 3 could be accessed by α-lithiation of N-phosphonate terminal aziridines 1, followed by N- to C-[1,2]-anionic phosphonyl group

• : lithiation-deuteration of N-diphenylphosphinylaziridine 10 gave the anticipated deuterated aziridine 11 (70%), along with the rearranged aziridine 12 (25%) [24] (Scheme 3). Results and Discussion So as to examine the migration chemistry outlined in Scheme 1, access to N-phosphonate terminal aziridines 1 was

Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

• Andreas Sundgren,
• Martina Lahmann and
• Stefan Oscarson

Beilstein J. Org. Chem. 2010, 6, 704–708, doi:10.3762/bjoc.6.80

• group from the primary position of the non-reducing end residue produced a free hydroxy group which was phosphorylated using H-phosphonate chemistry to yield the phosphoethanolamine-containing protected pentasaccharide. Partial deprotection afforded the phosphorylated target pentasaccharide with a free

• phosphoethanolamine. Compound 19 was also completely deprotected by sodium methoxide treatment followed by catalytic hydrogenolysis to give the non-phosphorylated target structure 20 (66%, Scheme 4), to be used as a reference in biological experiments. Earlier we used the Cbz-protected ethanolamine H-phosphonate

• monoester as a reagent in the formation of phosphoethanolamines [29]. Since the amino group in the spacer was already Cbz-protected and we wanted to be able to differentiate between the two amino groups during conjugation, a Boc-protected H-phosphonate monoester 21 was synthesised and used in the

A novel and efficient method to prepare 2-aryltetrahydrofuran-2-ylphosphonic acids

• Vsevolod V. Komissarov,
• Anatoly M. Kritzyn and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2010, 6, No. 63, doi:10.3762/bjoc.6.63

• [1][2][3][4]. As a part of our ongoing project, it seemed important to synthesize compounds with phosphonate and phenyl groups at one end of the hydrocarbon chain and a nucleic base residue at the other end. Previously, it was shown that compounds with similar structures inhibit purine nucleoside

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

• substance classes that have been mostly used in organic ammonium ion recognition: crown ethers, calixarenes [54], cyclodextrins [55][56][57], cucurbiturils, porphyrins, phosphonate based receptors, tripodal receptors, tweezer ligands, clefts, cyclopeptides and metal complexes. We have not included rotaxanes

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• deficient pyridines in the presence of trimethylsilyl triflate, tetrabutylammonium fluoride or a montmorillonite clay. The cyclisation precursor was synthesised by using the procedure of Hayashi [48] employing a Horner–Wadsworth–Emmons olefination between nicotinaldehyde and phosphonate 10. The resulting

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• chiral benzyl acetates were efficiently substituted employing low amounts of catalyst (1–5 mol%). While nitro-, cyano- and methyl ester derivatives gave remarkable anti-selectivity, the corresponding α-phosphonate showed high syn-selectivity. In general, the diastereoselectivity can be explained by

N-alkyl-N-(phosphonoethyl) substituted (meth)acrylamides – new adhesive monomers for self-etching self-priming one part dental adhesive

• Joachim E. Klee and
• Uwe Lehmann

Beilstein J. Org. Chem. 2009, 5, No. 72, doi:10.3762/bjoc.5.72

• , trimethylbromosilane, butylamine, 3,6-dioxaoctane-1,8-diamine, camphorquinone and 4-(N,N-dimethylamino)benzoic acid ethyl ester, diethyl (hydroxymethyl)phosphonate, 2,2′-azobisisobutyronitrile (AIBN) and 2,6-di-tert-butyl-4-methylphenol were purchased from Sigma-Aldrich and phenylbis(2,4,6-trimethylbenzoyl)phosphine

• ), 62.3 (2), 48.2 (5), 32.5 (4), 25.1 (3), 19.3 (10), 16.4 (1) ppm. 31P NMR (CH3OH-d4): δ = 21.0/21.3 and 24.6/26.0 ppm. Methacrylic acid phosphonomethyl ester (4): This compound was synthesized by esterification of methacrylic acid with diethyl (hydroxymethyl)phosphonate and subsequent methanolysis of

• phosphonic acids 3c, 3e, 3f and 3g in a formulation of an aqueous ethanol solution of N,N′-diethyl-1,3-bis(acrylamido)propane, phosphonic acid 3, and 3(4),8(9)-bis(acrylamidomethyl)tricyclo[5.2.1.02,6]decane. Synthesis of novel N-alkyl-N-(ethyl phosphonate) (meth)acrylamides 3. For 2a, 2b, 3a, 3b: R1 = H, x

Synthesis of phosphonate and phostone analogues of ribose-1-phosphates

• Pitak Nasomjai,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2009, 5, No. 37, doi:10.3762/bjoc.5.37

• Pitak Nasomjai David O'Hagan Alexandra M. Z. Slawin School of Chemistry and Centre for Biomolecular Sciences, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK 10.3762/bjoc.5.37 Abstract The synthesis of phosphonate analogues of ribose-1-phosphate and 5-fluoro-5-deoxyribose-1

• -phosphate is described. Preparations of both the α- and β-phosphonate anomers are reported for the ribose and 5-fluoro-5-deoxyribose series and a synthesis of the corresponding cyclic phostones of each α-ribose is also reported. These compounds have been prepared as tools to probe the details of

• both 5′-FDA and adenosine, and thus the presence or absence of fluorine at the C-5′-position is not a requisite for catalysis. The next enzymatic step involves a ring opening isomerisation of the ribose-1-phosphate 5. In this paper we report the synthesis of phosphonate analogues 8 and 9 of ribose-1

An expedient synthesis of 5-n-alkylresorcinols and novel 5-n-alkylresorcinol haptens

• Kirsti Parikka and
• Kristiina Wähälä

Beilstein J. Org. Chem. 2009, 5, No. 22, doi:10.3762/bjoc.5.22

• few papers have reported Wittig reactions in water without an organic solvent, although the related Horner-Wadsworth-Emmons reactions, using ester enolate type stabilized phosphonate ylids, have often been conducted in aqueous solutions [29]. The existing cases have mostly been targeted for the

Synthesis and redox behavior of new ferrocene- π-extended- dithiafulvalenes: An approach for anticipated organic conductors

• Abdelwareth A. O. Sarhan,
• Omar F. Mohammed and
• Taeko Izumi

Beilstein J. Org. Chem. 2009, 5, No. 6, doi:10.3762/bjoc.5.6

• derivatives 5a and 5b were synthesized cleanly and in high yields according to previously reported methods [12][13][15]. The 1,3-benzodithiole-2-phosphonate 6 was obtained in relatively high yield as described previously in literature [14][28][29]. Reaction of ferrocene-1,1′-dicarboxaldehyde (5a) or 1,1

• ′-diacetylferrocene (5b) with 1,3-benzodithiole-2-phosphonate (6) in dry THF in the presence of n-BuLi at −78 °C following the Wittig–Horner reaction method afforded the corresponding 1,1′-bis[(1,3-dithiol-2-ylidene)methyl]ferrocenes 7a and 7b in good yields (Scheme 1). The 1,1′-bis(1,3-dithiafulvalene)ferrocene 7a

• ]. However, upon reaction of the diacylferrocene 5c with the 1,3-benzodithiole-2-phosphonate 6 using a slight modification of the Wittig–Horner procedures, by carrying out the reaction at −20 to 0 °C and subsequently purifying by column chromatography using chloroform/hexane mixture, the 1,1′-bis(1,3-DTF)Fc