Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• of the agents. The degradation efficiency was found to be dependent on the relative position of the heterocycle towards the reactive group as well as on the nature of the organophosphorus derivative. Keywords: cyclodextrin; decontamination; enzyme mimic; nerve agents; organophosphorus pesticides

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• Supporting Information File 1, Table SI1) in the broken symmetry solution. The further conversion of the conformers of the intermediate diradical 12 into the macroheterocycle 9, the six-membered 1,4-dithiane 13, and the ten-membered heterocycle 14, respectively, is governed by two factors: the unpaired spin

• dimer 12, followed by the C–C bond formation involving the C(2) centers of the selenophene rings to yield the obtained twelve-membered heterocycle 9. In extension of the study, calculations were performed on the related symmetrical thiobenzophenone S-methanide by the same computational approach (see

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• could be synthesised by incorporation of CO2 from the supercritical solvent into the product. Keywords: continuous flow; heterocycle; N-alkylation; self-optimisation; supercritical CO2; Introduction N-alkylated amines are an important motif present in a range of pharmaceutically and industrially

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• determined using computational calculations. The values found for the HOMO coefficient and charge density were 0.009 and −0.259, respectively, which are small enough to promote the nucleophilic attack that leads to a heterocycle. The structures of all the compounds were confirmed by 1H and 13C NMR, LC–MS

3D printed fluidics with embedded analytic functionality for automated reaction optimisation

• Andrew J. Capel,
• Andrew Wright,
• Matthew J. Harding,
• George W. Weaver,
• Yuqi Li,
• Russell A. Harris,
• Steve Edmondson,
• Ruth D. Goodridge and
• Steven D. R. Christie

Beilstein J. Org. Chem. 2017, 13, 111–119, doi:10.3762/bjoc.13.14

• equipment, allowing automated online and inline optimisation of the reaction medium. This set-up allowed the optimisation of two reactions, a ketone functional group interconversion and a fused polycyclic heterocycle formation, via spectroscopic and chromatographic analysis. Keywords: 3D printing; inline

• allow a much larger chemical space to be analysed (<200 °C). The formation of a fused polycyclic heterocycle 5 (Scheme 2), from pentafluoropyridine (3) and 2-(methylamino)phenol (4), was chosen as this would generate a more complex optimisation set with two starting materials, the reaction product as

• the SIMPLEX optimisation of the fused polycyclic heterocycle 5. Two optimal data points at 0.24 mL/min and 156 °C, and 0.24 mL/min and 170 °C were found. SLM reactor design RD3 (left), CAD model of RD3 (right). External dimensions of RD3 are 89 (length) × 27 (width) × 38 mm (depth). Optimisation plot

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• electronegativity of the R group is probably also important; when more electropositive (as Si), the oxygen atoms become more electron rich and their repulsion becomes larger. Changing the conformation of a heterocycle has, as mentioned, been studied using the piperidine model system. The pKa of the corresponding

From betaines to anionic N-heterocyclic carbenes. Borane, gold, rhodium, and nickel complexes starting from an imidazoliumphenolate and its carbene tautomer

• Ming Liu,
• Jan C. Namyslo,
• Martin Nieger,
• Mika Polamo and
• Andreas Schmidt

Beilstein J. Org. Chem. 2016, 12, 2673–2681, doi:10.3762/bjoc.12.264

• ], versatile organocatalysts [8][9][10], and starting materials for heterocycle syntheses [11][12][13]. Consequently books [14][15][16] and reviews cover the range from NHC structures in the light of their early history [17], syntheses [6][18], coordination chemistry [19][20], and catalysis [21][22], to

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• the bases is a substrate for both enzymes, UP and TP, and the glycosylation efficiency depends, as might be expected, on the C-5 substituent of the heterocycle, viz., glycosylation of 6-azauracil occurs more efficiently under UP catalysis, whereas the 6-azathymine synthesis proceeds more efficiently

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• alkaloids are a small subgroup of flavonoids possessing a five- or six-membered nitrogen heterocycle attached to C-6 or C-8 of ring A of the flavonoid moiety. They have been reported to exhibit a wide range of pharmacological activities [1]. Dracocephins A and B were isolated as a mixture of four

Sydnone C-4 heteroarylation with an indolizine ring via Chichibabin indolizine synthesis

• Florin Albota,
• Mino R. Caira,
• Constantin Draghici,
• Florea Dumitrascu and
• Denisa E. Dumitrescu

Beilstein J. Org. Chem. 2016, 12, 2503–2510, doi:10.3762/bjoc.12.245

• sydnone ring. From a survey of the literature data [6][7][8][9][10][11][12][13][14][15] and based on our previous findings [16][17][18][19] it was concluded that the heterocycle in the pyrroloazine series most suitable for this study would be indolizine (2). Indolizine or pyrrolo[1,2-a]pyridine (2) and

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• traditional way this heterocycle is synthesized from urea, aldehydes, and 1,3-diketones. The method described in this work is quite general and can be applied to any monocyclic structure. The Supporting Information contains an atlas of target bond dissection maps applied to 27 kinds of heterocyclic structures

• -membered heterocycle containing two adjacent nitrogen atoms. Pyrazole Pyrazole is a well-studied 5-membered heterocycle that has been traditionally synthesized either via the Knorr [151] (1,3-diketone and hydrazine) or von Pechmann [152] (olefin and diazomethane followed by oxidation) strategies. Figure 7

• 1,3-diketones, urea, and aldehydes. A full integer partitioning and target bond dissection mapping analysis for three-component couplings of this heterocycle, as shown in Figure 9, indicates that the chemical space consists of twelve [3 + 2 + 1], six [4 + 1 + 1], and two [2 + 2 + 2] possible

Selective and eco-friendly procedures for the synthesis of benzimidazole derivatives. The role of the Er(OTf)₃ catalyst in the reaction selectivity

• Natividad Herrera Cano,
• Jorge G. Uranga,
• Mónica Nardi,
• Antonio Procopio,
• Daniel A. Wunderlin and
• Ana N. Santiago

Beilstein J. Org. Chem. 2016, 12, 2410–2419, doi:10.3762/bjoc.12.235

• ) trifluoromethanesulfonate; green procedure; heterocycle; Introduction The formation of heterocyclic compounds is a very important task in organic synthesis, mainly because they are present in numerous biologically active compounds and in several natural products [1]. Among them the presence of benzimidazole [2][3][4][5][6

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• to afford a spirocyclic sulfur-bridged N-heterocycle 4 in 70% yield and without compromising its ee value. Conclusion In conclusion, we have developed the first asymmetric reaction of 5H-thiazol-4-ones with N-itaconimides. By employing a DP-UAA catalyst, the reaction undergoes a [4 + 2] annulation

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• the synthesis of dispiro compounds comprising pyrrolidine, oxindole, and other heterocycle moieties and to the evaluation of their physiological properties [24][26][27][28][29][30][31][32]. In this regard, our attention was directed towards hetero-annelated 1,2,4-triazines, because this motif is part

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• widespread in peptidic natural products of both, non-ribosomal and post-ribosomal modified origin [5]. The biosynthetic mechanisms for heterocycle formation are numerous, and range from simple addition or condensation reactions to oxidative ring closures. The large number of mechanistically different

• cyclisation modes triggers the interest on the responsible enzymes. Due to the relevance of heterocycles, understanding the enzymology of heterocycle formation is also an important milestone on the way to using the enzymes as chemoenzymatic tools in natural product synthesis and medicinal chemistry [6][7

• ). This review intends to give an overview on the mechanisms involved in heterocycle formation during polyketide biosynthesis. A focus will be placed on oxygen and nitrogen-containing heterocycles due to their abundance and relevance. Although the genuine polyketide biosynthesis machinery does not harbour

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• compound high flexibility. Initially reported by K. Seley-Radtke’s group, the replacement of the nucleobase by a “flexi-moiety” where the imidazole ring and a six-membered heterocycle is linked through a C–C bond lead to new derivatives behaving as nucleosides and even as enzyme inhibitors [11][12][13

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• DMPTMS as a nucleophilic reagent on the N-protonated heterocycle followed by a 1,2-addition of DMPTMS on the N-silylated species lead to the diphosphorylated heterocycles after aqueous work-up. 8 Miscellaneous multicomponent reactions The reaction of pentanedial (284) with acetamide (283) and acetyl

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• then be attacked by an adjacent serine or cysteine side chain, thus releasing phosphate/AMP and generating the heterocycle. This order of steps was not advocated by either the Naismith or Mitchell groups as it requires a disfavoured 5-endo-trig cyclisation, although this mode of cyclisation is

• there remains a wealth of unexplored pathways to discover and characterise. Schematic of RiPP biosynthesis. Thiazole/oxazole formation is represented by the blue heterocycle (X = S, O), lanthionine formation is represented by the purple cross-link (X = S) and macrolactam (X = N) or macrolactone (X = O

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• steps. Heterocycle 7 is a bench stable white powder that can be stored indefinitely in a dessicator without any noticeable decomposition. The sulfonamide moiety activates sulfur towards nucleophilic addition, making the first addition of an organometallic reagent faster than the second. By performing

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• further studies for modular heterocycle synthesis. Experimental Preparation of 31 by asymmetric addition of allylmagnesium bromide to 29 In a flame-dried flask (SS)-N-(1-((tert-butyldimethylsilyl)oxy)propan-2-ylidene)-2-methylpropane-2-sulfinamide (29, 1.37 g, 4.70 mmol, 1.0 equiv) was dissolved in 12 mL

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• constructing biologically important spirooxindoles. In addition to the above mentioned metal- and organocatalyzed asymmetric synthesis of 3-hydroxyoxindoles, Zhao et al. reported a complementary strategy that employed the chiral acylazolium species (prepared from aldehydes and N-heterocycle carbenes) to

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• -mercapto acids (X = S) depending on the nature of the starting heterocycle. This review describes the first examples and applications of 1H-imidazol-4(5H)-ones 1 and thiazol-4(5H)-ones 2 (Figure 2) as emerging pronucleophiles in asymmetric catalytic reactions. Review 1 1H-Imidazol-4(5H)-ones 1 α,α

• ]. The main advantages of these pronucleophiles over the previous known templates are: i) the NR group can be installed in the heterocycle previous to the asymmetric reaction, ii) they are easily deprotonated under soft enolization conditions (aromatic enolate formation), and iii) unlike azlactones and

• reaction conditions the authors found that thiazolones 74 bearing either short, large or ramified alkyl chains at the heterocycle afforded the corresponding Michael adducts in good yields and excellent enantioselectivity in the presence of 20 mol % of catalyst C3 (Scheme 13). Initial attempts to carry out

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• desired azacycloalkenes 102a–c in 95–98% yield and 92–95 % ee (Table 11). Only the diene 100d did not cyclize and did not afford the nine-membered heterocycle by this methodology. In 2015, Hashimoto et al reported the synthesis of methyl 2-vinyltetrahydropyran-3-carboxylates (104) by an enantioselective

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

• Grzegorz Mlostoń,
• Paulina Pipiak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 716–724, doi:10.3762/bjoc.12.71

• . In addition, the structure of the sterically crowded 4,4,5,5-tetrasubstituted aryl/hetaryl 1,3-dithiolanes 10 could be confirmed by the presence of only two signals for the three C(sp3)-atoms of the heterocycle, whereas in the isomeric 2,2,4,4-tetraaryl/hetaryl 1,3-dithiolanes, three signals for

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• : α-lithiation; C–H functionalization; heterocycle; photoredox catalysis; piperazine; Introduction Piperazine is one of the most important saturated N-heterocycles frequently found in life-saving small-molecule pharmaceuticals [1]. In a recent statistical study done by Njardarson and co-workers