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

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

• sulfone is necessary: when the Mannich reaction of benzothiepinone 65b with formaldehyde was attempted, the reaction resulted in the formation of novel tricyclic sulfonium 69 in modest yield [32]. It is also possible to profit from the ability of xanthates to mediate additions to olefins containing

Synthesis of meso-substituted dihydro-1,3-oxazinoporphyrins

• Satyasheel Sharma and
• Mahendra Nath

Beilstein J. Org. Chem. 2013, 9, 496–502, doi:10.3762/bjoc.9.53

• condensation–cyclization reaction of 5-(4-aminophenyl)-10,15,20-triphenylporphyrin (1) with α- or β-naphthol and formaldehyde in THF under reflux. After reaction with Zn(OAc)2·2H2O in CHCl3/MeOH mixture, the free-base naphthoxazinoporphyrins 14 and 16 underwent zinc insertion to afford zinc (II) dihydro-1,3

• -dihydroxynaphthalenes and formaldehyde in THF under reflux (Scheme 3). Attempts have also been made to prepare the corresponding zinc naphthoxazinoporphyrin dyads, but always impure products were obtained even after repeated column chromatography. The newly synthesized porphyrins were characterized on the basis of 1H

A new intermediate in the Prins reaction

• Shinichi Yamabe,
• Takeshi Fukuda and
• Shoko Yamazaki

Beilstein J. Org. Chem. 2013, 9, 476–485, doi:10.3762/bjoc.9.51

• produced when pinene (a bicyclic monoterpene) was heated with paraformaldehyde. However, Prins performed the first rather comprehensive study of the reactions between formaldehyde and hydrocarbons with C=C double bonds [2][3]. These were styrene, pinene, camphene and anethole. As a catalyst, sulfuric acid

• hand, a reaction of longifolene with formaldehyde in acetic acid yielded the acetate of an allylic alcohol (ω-acetoxymethyl longifolene) as a major product under high-temperature conditions (Scheme 4, 140 °C, 24 h) [5]. A scheme was proposed as to the mechanism of the Prins reactions [6][7][8][9][10

• , because the constituent atoms are only C, H and O in the original system, and it is a fundamental organic reaction. In this work, as the first attempt, reactions paths were traced by DFT calculations under Prins’ original conditions (styrene and formaldehyde in the acidic aqueous media). As an alkene

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

• used directly in the next step without purification. Compound 4 was first treated with sodium hydride or other bases and then reacted with formaldehyde to form terminal alkene 5 through a Horner–Wadsworth–Emmons reaction [12] (two-step overall yields are 27%, 53% and 55% for 3a to 5a, 3b to 5b and 3c

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• /ethyl acetate (3:2), N-methylation and N-formylation were observed (Supporting Information File 1). Considering prior evidence that methanol can generate formaldehyde in the presence of Pd(0) by an oxidative addition mechanism [43][44] and the observation that apolar solvents cause N-formylation during

New enzymatically polymerized copolymers from 4-tert-butylphenol and 4-ferrocenylphenol and their modification and inclusion complexes with β-cyclodextrin

• Adam Mondrzyk,
• Beate Mondrzik,
• Sabrina Gingter and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 2118–2123, doi:10.3762/bjoc.8.238

• complexes; polymer-analogous modification; Introduction Polyphenols in general play an important role in nature, e.g., lignin and suberin. In industry, Bakelite represents the first practically successful polyphenol resin [1]. In the latter case, the phenol moieties are covalently connected by formaldehyde

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• ammonia or an ammonia equivalent, such as 2,4-dimethoxybenzylamine (DMB-NH2), as amino component, formaldehyde as oxo-component, and a convertible isonitrile [22][23][24][25]. Although many convertible isonitriles are reported in the literature [24][26], the recently developed 4-isocyanopermethylbutane

• -1,1,3-triol (IPB) was chosen due to its ease of preparation, better reactivity, and mild conversion conditions [27]. The Ugi-4CR involving carboxylic acid 9, DMB-NH2, formaldehyde and IPB resulted in intermediate 11 in 35% yield. A tandem DMB group cleavage/pyrrole-formation sequence under acidic

• -Dimethoxybenzylamine, formaldehyde, IPB, MeOH, rt, 18 h, 35%. (d) TFA, CH2Cl2, 0 °C to rt, 48 h, then LiOH, THF/H2O (1:1), rt, 3 h, 21% (over two steps). (e) MeOH, rt, 20 h, 51–70%. (f) LiOH, THF/H2O, rt, 8 h, 81–91%. (g) KOH, MeOH/H2O (3:1), rt, 8 h, 70%. Supporting Information Supporting Information File 311

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

New efficient ligand for sub-mol % copper-catalyzed C–N cross-coupling reactions running under air

• Per-Fredrik Larsson,
• Peter Astvik and
• Per-Ola Norrby

Beilstein J. Org. Chem. 2012, 8, 1909–1915, doi:10.3762/bjoc.8.221

• lowering the copper concentration, dimethyldiethylene triamine (DMDETA) was a natural choice as ligand. The ligand was synthesized based on literature procedures starting from diethylene triamine (Scheme 1) [85][86]. Reductive methylation by using formaldehyde and NaBH4, as well as BOC-protection followed

Imidazolinium and amidinium salts as Lewis acid organocatalysts

• Oksana Sereda,
• Nicole Clemens,
• Tatjana Heckel and
• René Wilhelm

Beilstein J. Org. Chem. 2012, 8, 1798–1803, doi:10.3762/bjoc.8.205

• ammonium tetrafluoroborate followed by anion metathesis in 33 and 29% yield, respectively. Due to the low yield, salt 21 was prepared through a different route. First amine 27 [30] was transformed with formaldehyde to the aminal 28. The latter could be oxidized to the corresponding bromide salt, which was

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• of (S)-2 with 2 equiv of formaldehyde in formic acid under Eschweiler–Clarke conditions led to N-methylated sulfoximine (S)-6 in 91% yield [55][56]. The α-nitro group was introduced under conditions reported by Wade [57]. Thus, deprotonation of (S)-6 in tetrahydrofuran (THF) with potassium bis

Synthesis and in silico screening of a library of β-carboline-containing compounds

• Kay M. Brummond,
• John R. Goodell,
• Matthew G. LaPorte,
• Lirong Wang and
• Xiang-Qun Xie

Beilstein J. Org. Chem. 2012, 8, 1048–1058, doi:10.3762/bjoc.8.117

• } under acidic conditions to produce the corresponding products in yields ranging from 54–89%. A range of aldehydes were accommodated in the Pictet–Spengler reaction, including formaldehyde (Table 1, entry 1), alkyl aldehydes (Table 1, entries 2 and 3), aryl aldehydes with electron-withdrawing and

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• stereochemistry of the major diastereomer 6e was assigned unambiguously by single-crystal X-ray analysis. With a range of suitable test substrates in hand, formaldehyde-derived imines were then investigated in the nitro-Mannich/lactamisation reaction. Aqueous formaldehyde (3a) and allylamine (4a) were added to a

• established by 1H NMR spectroscopic analysis. For more details on the elucidation of the relative configuration see [61] and Supporting Information File 1. To incorporate substituents at the 6 position of the piperidine ring in 1, imines derived from aldehydes other than formaldehyde were required in the

• diastereoisomers in good yields (82% and 75%) when nitro-Mannich/lactamisation cascades were carried out with formaldehyde (3a) and butylamine (4c) or hept-5-yn-1-amine (4d), respectively. To extend the cascade methodology to the potential construction of architecturally complex piperidine-ring-containing

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22

• heating 2,6-bis(hydroxymethyl)-4-tert-butylphenol [11]. Elemental analysis gave an empirical formula of C12H16O2 and molecular weight determinations gave values corresponding to a trimer. Despite interest in novel phenol–formaldehyde polymers and macrocycles and characterization of 3a in 1979 [13], it

Synthesis of (−)-julocrotine and a diversity oriented Ugi-approach to analogues and probes

• Ricardo A. W. Neves Filho,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2011, 7, 1504–1507, doi:10.3762/bjoc.7.175

• , and melting point of 1 were consistent with the reported data [2][14][15]. For the diversity oriented synthesis the advanced intermediate 5 was used as the amino component in an Ugi-4CR with (S)-2-methylbutanoic acid, hydrophobic amino acids, formaldehyde and tert-butyl isocyanide (Scheme 2). These

• analogues possess a protease-resistant peptoid scaffold and this might lead to an enhanced activity [19][20]. In this endeavor, all Ugi reactions were initiated by pre-imine formation of 5 and reaction with formaldehyde as the oxo-component, after which the multicomponent reaction was completed by the

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• , Figure 3) was also produced, but was readily separable from the desired product by flash chromatography. Unfortunately, reaction of the tetralithio intermediate 8 with carbonyl electrophiles (e.g., acetone, acetaldehyde, diethyl carbonate, valeraldehyde, cyclohexanal, crotonaldehyde, formaldehyde, DMF

Ugi post-condensation copper-triggered oxidative cascade towards pyrazoles

• Aurélie Dos Santos,
• Laurent El Kaim,
• Laurence Grimaud and
• Caroline Ronsseray

Beilstein J. Org. Chem. 2011, 7, 1310–1314, doi:10.3762/bjoc.7.153

• reactions [14][15][16][17][18][19][20][21][22][23], however, to the best of our knowledge, there is no report involving α-hydrazonocarboxylic acids. Hydrazone 1a was prepared through condensation of pyruvic acid with phenylhydrazine. Adding 1a to aqueous formaldehyde, allylamine and tert-butylisocyanide in

• these optimized conditions. Results are reported in Table 1. Surprisingly, the reaction appears to be only efficient with Ugi adducts prepared with formaldehyde as the carbonyl component (Table 1, entries 1–5). With other aldehydes and ketones, even if the Ugi reaction was performed easily, the

• reaction with N-alkyl hydrazones: An attempt of Ugi coupling with hydrazone 1d, formaldehyde, allylamine and tert-butylisocyanide failed to give any isolable adduct (Scheme 3). This may be explained by an enhanced nucleophilicity of the N-monoalkyl hydrazone leading to a competition between the hydrazone