NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• starting material, one challenge was to avoid unwanted side reactions resulting from the generation of formaldehyde in the reaction mixture. Hydrogenolysis of the BOM group affords toluene and formaldehyde as byproducts, and the Cbz-deprotected 6'-amino group can undergo unwanted reductive amination, i.e

• ., methylation, with the liberated formaldehyde. Our method to prevent this side reaction was to include an excess of n-butylamine as an additive in the reaction mixture of the hydrogenolysis step. This way, the formaldehyde methylated the added n-butylamine, furnishing a reasonably volatile byproduct [38][48

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• environment [23]. The toxicity of some biocides has been particularly well described. As examples glutaraldehyde and amphiphilic ammonium have been associated with dermatitis [24][25]. Toxicity, hypersensitivity and irritation have also been reported with other biocides such as formaldehyde [26

An integrated photocatalytic/enzymatic system for the reduction of CO₂ to methanol in bioglycerol–water

• Michele Aresta,
• Angela Dibenedetto,
• Tomasz Baran,
• Antonella Angelini,
• Przemysław Łabuz and
• Wojciech Macyk

Beilstein J. Org. Chem. 2014, 10, 2556–2565, doi:10.3762/bjoc.10.267

• , namely: formate dehydrogenase (FateDH), formaldehyde dehydrogenase (FaldDH), and alcohol dehydrogenase (ADH). These enzymes promote the cascade reduction of CO2 to methanol through formic acid (FateDH), formaldehyde (FaldDH) and aldehyde (ADH). The reduction process is enabled by NADH, which is oxidized

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• , numerous pilot scale processes have been demonstrated like the electrohydrodimerization of formaldehyde to ethylene glycol [36] or the production of glyoxylic acid [37]. The most important reasons for this raised interest are the higher energy efficiency compared to traditional thermochemical processes

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• .10.230 Abstract Novel cis/trans-4- and cis/trans-5-(2-vinylstyryl)oxazoles have been synthesized by Wittig reactions from the diphosphonium salt of α,α’-o-xylene dibromide, formaldehyde and 4- and 5-oxazolecarbaldehydes, respectively. In contrast, trans-5-(2-vinylstyryl)oxazole has been synthesized by

• /trans-Isomers of 4- and 5-oxazole derivatives (1, 2) were synthesized by Wittig reactions from the diphosphonium salt of α,α’-o-xylene dibromide, formaldehyde and oxazole-4- and 5-carbaldehydes (3, 4), respectively, in absolute ethanol with sodium ethoxide as a base (Scheme 1). The procedure of this

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

• derivatives 7–10 were prepared from pyrrolidine azanucleosides 15a–d [5][15] via a Mannich-type reaction with diisopropyl phosphite and aqueous formaldehyde at elevated temperature in good yields (Scheme 1). The obtained diisopropyl esters 17a–d were deprotected by treatment with trimethylsilyl bromide in

Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

• Maroš Bella,
• Bohumil Steiner,
• Vratislav Langer and
• Miroslav Koóš

Beilstein J. Org. Chem. 2014, 10, 1942–1950, doi:10.3762/bjoc.10.202

• ), produced by an addition of the Grignard reagent 10 to the monomeric formaldehyde (11, R1 = R2 = H), was unstable and decomposed by a reversible process into the Grignard reagent and aldehyde. The latter underwent a Prins-type reaction with the magnesium alkoxide intermediate E in the presence of MgCl2, to

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• Mannich reaction using dibenzylamine–formaldehyde and 2-acylaminopyrrolo[2,3-d]pyrimidin-4(3H)-one, which resulted in the selective introduction of the dibenzylaminomethyl group [10]. The following amine exchange reaction of the dibenzylamine function in the Mannich base with ammonia resulted in the preQ1

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• as Mannich bases) can serve as starting materials in the syntheses of a variety of compounds. The employment of a nucleoside as the hydrogen active component has been one of the most common variants of the Mannich reaction. Treatment of uracil (or 2-thiouracil) nucleosides 1 with aq formaldehyde and

• involving taurine, formaldehyde and 2',3'-O-isopropylideneuridine [61]. Watanabe et al. described the synthesis of 7-(morpholinomethyl)tubercidin 5 by heating tubercidin, 37% aq formaldehyde and morpholine at 90 °C overnight (Scheme 3) [62]. Compound 5 was converted into the natural nucleoside toyocamycin

• pyrrolidine hydrochlorides 16*HCl or 20a–c*HCl (Scheme 8), Evans et al. developed a concise synthesis of 1'-aza-analogs of immucilins, compounds 19 and 21 [67]. The amine hydrochlorides were treated in aq acetate buffer with aq formaldehyde and 9-deazaguanine 18a or a variety of deazapurines 18b–e. The

Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

• Axel G. Griesbeck and
• Melissa Reckenthäler

Beilstein J. Org. Chem. 2014, 10, 1143–1150, doi:10.3762/bjoc.10.114

• changes in conversion and chemoselectivity. The formation of formaldehyde as the final oxidation product was proven qualitatively (colorless precipitation of polyformaldehyde was observed in most experiments) and by a GC–MS online detection of monomeric formaldehyde. From these results, we reasoned that

• the photolysis of TiO2 in the absence of additional acceptor compounds with formation of hydrogen and eventually formation of formaldehyde [46]. Both hydrogen and formaldehyde were also detected in our experiments by gas-phase analysis. Thus, higher amounts of hydroxymethyl radicals can be produced

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• the great electrophilicity of circumtrindene in the Bingel–Hirsch reaction, it came as no surprise that circumtrindene can act as a good dipolarophile in a [3 + 2] cycloaddition reaction as well. Accordingly, the azomethine ylide 23 generated in situ from N-methylglycine and formaldehyde adds to

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• NaHCO3, as a viscous undistillable liquid, which was stable for weeks on storage. Three-component reactions At the outset of our work three-component reactions of formaldehyde, dibenzylamine and the esters 2 or 5 were explored as model transformations to evaluate the feasibility of the Kabachnik–Fields

• formaldehyde, forming (α-hydroxymethyl)phosphinate 8. Its further irreversible rearrangement [28] to the corresponding phosphonate 9 was accompanied with hydrolysis of the ester function and formation of (trifluoromethyl)phosphonic acid (10) [29] as the main product. Analogous results were obtained, when CHF2

• . This resulted in the preparation of the analogues of glycine 14a and phenylglycine 14b (Scheme 3). The three-component reaction with formaldehyde gave the best results and N-protected aminophosphinic acid 13a was isolated in a moderate yield, alongside phosphonic acid 10. The analogous reaction with

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• secondary amines, as well as aryl and alkyl-substituted alkynes (Scheme 2). It is noteworthy that the approach tolerated challenging substrates such as formaldehyde, o-substituted benzaldehydes, and secondary aromatic amines. Moreover, the PS–NHC–Ag(I) catalyst was proven to be reusable at least 12 times

• leads to formaldehyde and ammonia, so that in the presence of silver salt the well-known silver mirror reaction could take place, thus justifying the need of at least one equiv of AgNO3. A silver supramolecular complex was proposed by Sun and co-workers as an efficient catalyst for A3-coupling reactions

• catalysis), was recently suggested by the group of Scaiano and González-Béjar [32] as a mild and green system to perform A3-MCRs. The scope was concisely explored crossing three different aldehydes (i.e., benzaldehyde, formaldehyde and 3-methylbutanal) with phenylacetylene, and three cyclic secondary amines

Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

• Murat Kucukdisli,
• Dorota Ferenc,
• Marcel Heinz,
• Christine Wiebe and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 466–470, doi:10.3762/bjoc.10.44

• or ketones [23]. The most practical approach to a 2,4-disubstituted pyrrole reported to date is the recently disclosed microwave-assisted Stetter reaction of chalcone with carbohydrates as “green” formaldehyde equivalents followed by a microwave-assisted Paal–Knorr cyclization of the resulting 1,4

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• 5 were obtained in pure form in 78–94% yields (Scheme 2 and Table 2). It is noteworthy, that a similar reaction, in which the less hindered, more reactive formaldehyde was employed as the aldehyde component, took a completely divergent course and afforded 5-arylcarbonyl-1,3

• -diarylhexahydropyrimidines arising from pseudo five-component reactions of (E)-3-(dimethylamino)-1-arylprop-2-en-1-ones, two molecules of formaldehyde and two molecules of aniline [55]. The structure of compounds 5 was deduced from one and two-dimensional NMR spectroscopic data, as detailed in Supporting Information File 1

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• phosphorochloridate), 80% over two steps, Scheme 1). N,N-Dimethylisoleucine (10), obtained by reductive dimethylation of isoleucine with aqueous formaldehyde and H2 on Pd/C [10][11], was appended at the N-terminus (DEPC, diethyl phosphorocyanidate) affording tripeptide tert-butyl ester 11. Treatment with TFA

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• in situ generated formaldehyde (dehydrogenation of methanol) [50][51][52][53] and subsequent aminal formation with aminooxepanes 26 and 27. The aminoalcohol 28 seems not to form the corresponding compounds. We suppose that bicyclic compound 28 is more strained and hence the formation of a third ring

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• reaction proceeds via the formation of ozonide 73 followed by elimination of formaldehyde to give peroxycarbenium ion 74 that undergoes cyclization via the attack of the hydroperoxide group on the carbon center of peroxycarbenium ion 74 (Scheme 22) [254]. Spirohydroperoxydioxolane 75a (n = 1) was obtained

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• treatment of 3 gave a cloudy suspension, with decomposition products evident in the 1H NMR spectrum. We next targeted hydroxymethyl substituents. Treatment of 1 with aqueous formaldehyde (40% w/v) and Amberlyst-15® resin at room temperature [27] gave complex mixtures of products. However, heating 1 with

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• , formaldehyde and ammonia (Scheme 1, C). Likewise numerous methods of synthesising substituted pyridines have been reported [15]. Much of this development was stimulated by the discovery of pharmaceutically active pyridine containing biogenic structures but mainly in an industrial context by the drive for new

• flow process at their main plant in Visp, Switzerland. An alternative process is based on the availability of 3-picoline (1.15) which is generated as a major side product in the synthesis of pyridine prepared from formaldehyde, acetaldehyde and ammonia in a gas phase reaction (Scheme 3) [25]. The 3

• elevated temperatures and pressures 2-methyl-5-ethylpyridine undergoes a condensation reaction with formaldehyde allowing isolation of the chain extended hydroxyethylpyridine 1.70 upon distillation although in poor yield [44]. Following subsequent SNAr reaction aryl ether 1.71 is obtained, which is used as

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• condensation of primary amines with o-diacylbenzene 19 (Scheme 2) [13]. After initial formation of 20, isomerization to 21 and 22 can occur through a sequential dehydration–hydration process. Dimerization of 21 and 22 generates 23, the substrate for a formal retro-Aldol reaction. Loss of formaldehyde gives 24

Thermochemistry and photochemistry of spiroketals derived from indan-2-one: Stepwise processes versus coarctate fragmentations

• Götz Bucher,
• Gernot Heitmann and
• Rainer Herges

Beilstein J. Org. Chem. 2013, 9, 1668–1676, doi:10.3762/bjoc.9.191

• as 1:27. Figure 4 shows an infrared spectrum of the pyrolysis products. The organic products include formaldehyde (FA), acetaldehyde (AA), ethene (ET), o-xylylene (XY), benzocyclobutene (BC), styrene (ST), and indan-2-one (IN). Some peaks could not be assigned. The assignment of the pyrolysis

• . Relative to [CO2] = 1.0, the concentrations of the other pyrolysis products are as follows: [CO] = 27.2, [IN] = 3.8, [ET] = 15.9, [BC] = 11.4, [XY] = 1.3, [AA] = 3.9 [25]. Formaldehyde is formed as a minor product only. The photochemistry of ketals 2 and 3 was investigated as well by matrix isolation

• ). Organic products include mostly FA, ET, and IN, as well as BC and XY, but many peaks have to remain unassigned. Propene was not formed. Compared to the FVP of 1, the FVP of 2 yields significantly increased amounts of 2-indanone and formaldehyde. Relative to [CO2] = 1.0, the concentrations of the other

Dipolar addition to cyclic vinyl sulfones leading to dual conformation tricycles

• Steven S. Y. Wong,
• Michael G. Brant,
• Christopher Barr,
• Allen G. Oliver and
• Jeremy E. Wulff

Beilstein J. Org. Chem. 2013, 9, 1419–1425, doi:10.3762/bjoc.9.159

• ). We were pleased to observe a tetracyclic product in this case (albeit in modest yield) but were surprised to find that the anisole ring was not included in the isolated compound. Indeed, adduct 4 appeared to result from transiminization of dipole 2a with formaldehyde (generated by the thermal

A³-Coupling catalyzed by robust Au nanoparticles covalently bonded to HS-functionalized cellulose nanocrystalline films

• Jian-Lin Huang,
• Derek G. Gray and
• Chao-Jun Li

Beilstein J. Org. Chem. 2013, 9, 1388–1396, doi:10.3762/bjoc.9.155

• formaldehyde, piperidine, and phenylacetylene. It is important to verify that the actual catalytic process is heterogeneous and not homogeneous [39]. For this reason, we did the following experiment: the solid catalyst was removed by filtering when the conversion was up to 45% in A3-coupling reactions, and

• then the solution reaction was continued under the same conditions. The conversion of the formaldehyde did not significantly increase, which strongly suggested that this catalytic process was a heterogeneous process. Conclusion In summary, this work developed a new approach to design Au nanoparticles

• @HS-CNC (4.4 mol %) catalyst for the three-component coupling of formaldehyde, piperidine, and phenylacetylene (A3-coupling) under solvent-free conditions. Sketch illustrating preparation of the Au@HS-CNC catalyst. Three-component coupling of benzaldehyde, piperidine, and phenylacetylene catalyzed by