Mechanistic studies on the CAN-mediated intramolecular cyclization of δ-aryl-β-dicarbonyl compounds

• Brian M. Casey,
• Dhandapani V. Sadasivam and
• Robert A. Flowers II

Beilstein J. Org. Chem. 2013, 9, 1472–1479, doi:10.3762/bjoc.9.167

• obtain a better understanding of the impact of arene substitution on the intramolecular cyclization, DFT calculations were performed at UB3LYP/6-31G(d) level by using Gaussian 03/09 [28]. Previous research from our group has shown that the oxidation of the enol tautomer of a diketone initially forms a

• obtain the minima. For the aryl diketone radical, two conformers for the ketones were considered, one with the carbonyl groups syn to each other and the other with the carbonyl groups in the anti orientation. For every substrate, two transition structures were identified on the energy surface along the

• compared to the parent aryl diketone radical, and the rotational transition structure has a comparable barrier of 2.5 kcal/mol. While it is evident why electron-rich systems should more readily cyclize, the observed site selectivity in products 2g and 2j warranted further investigation. For these

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• represents an efficient route toward a diversity-oriented synthesis of several Illicium sesquiterpenes. The enantioselective entry to these molecules is based on an organocatalyzed asymmetric Robinson annulation that allows access to the enantiomerically enriched bicyclic motif 8 from achiral diketone 11

• enantioselectivity and short reaction time, we decided to pursue this conversion at 40 °C where we obtained an enantiomeric excess of 90% (70% yield after 14 days). The enantiomerically enriched Hajos–Wiechert-like diketone 8 (ee > 90%) was then subjected to a selective protection of the C-6 enone motif to yield

Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

• Mostafa Kiamehr,
• Firouz Matloubi Moghaddam,
• Satenik Mkrtchyan,
• Volodymyr Semeniuchenko,
• Linda Supe,
• Alexander Villinger,
• Peter Langer and
• Viktor O. Iaroshenko

Beilstein J. Org. Chem. 2013, 9, 1119–1126, doi:10.3762/bjoc.9.124

• pyridinium salt 2a should be used in a ratio of two to one. In addition, the optimization study showed the essential role of a non-nucleophilic base as well as that of the potassium cation. This optimization study afforded a general procedure and optimal reaction conditions: 2.0 mmol of diketone, 1.0 mmol of

• -diketone deprotonation and nucleophilic attack of potassium 3-oxocyclohex-1-enolate on pyridinium cation, which yields an intermediate with a new C–C bond, and this is a key stage in the reaction. The C–O bond formation can be excluded in the initial stage (see Supporting Information File 2 for the

• because this base is presumed to operate; it is formed from neutral carbonate when it deprotonates the cyclic diketone. However, the mechanism involving any other base should not differ significantly. A plausible mechanism is presented in Figure 2. After initial deprotonation of the diketone and formation

Substituent effect on the energy barrier for σ-bond formation from π-single-bonded species, singlet 2,2-dialkoxycyclopentane-1,3-diyls

• Jianhuai Ye,
• Yoshihisa Fujiwara and
• Manabu Abe

Beilstein J. Org. Chem. 2013, 9, 925–933, doi:10.3762/bjoc.9.106

• cyclopentadienes, and followed by a hydrogenation reaction [30][31]. The synthesis of AZg (Ar = 3,5-dimethoxyphenyl, Ar’ = H) was performed from the corresponding 1,3-diketone 4 (Scheme 3b). 2,2-Dimethoxy-1,3-diarylpropane-1,3-dione 5g was prepared from 1,3-dione 4 (R = 3,5-dimethoxybenzene) according to the

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• -membered 25 was induced by treatment with NaNO2 in acetic acid [28][29], resulting in the formation of eight-membered 27 through the intermediary of 26. Finally, the desilylation of 27 with TBAF and the subsequent oxidation of the resultant hydroxy group delivered the symmetric diketone 1 in optically

• ; found, 331.2078. C2-symmetric diketone 1: TBAF (1.0 M in THF, 130 μL, 0.13 mmol) was added to a solution of 27 (13 mg, 42 μmol) in THF (0.9 mL) at room temperature. The reaction mixture was stirred for 1.5 h at room temperature and at 40 °C for 1.5 h. TBAF (1.0 M in THF, 83 μL, 83 μmol) was added again

• mL × 3). The combined organic layers were washed with brine (5 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (silica gel 1 g, pentane/Et2O 5:1 to 2:1) to afford C2-symmetric diketone 1 (7.5 mg, 39 μmol) in 93% yield over two steps: crystal

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

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

• reaction. In this case the diketone 107 was obtained by a Zn/Cu-couple-induced coupling reaction between excess phenacyl bromide (105) and the enyne 106 (Scheme 27) [83]. Besides 107 its diyne and propargylallene dimers were produced, requiring a chromatographic separation of the product mixture. The

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• catalysts were screened in the reaction of phenyl disubstituted unsaturated 1,4-diketone 1a with diethyl malonate (2a, Table 1). The reaction was run in DCE at room temperature in the presence of 10 mol % of catalyst with a five-fold excess of malonate. In all cases, the yields of the products were very

• ) was used. This did not influence the reaction time or the enantioselectivity, but afforded easier purification of the crude product. 1,4-Diketone 1a reacted smoothly with a variety of malonates 2a–2f, affording the products 3a–3f in high yields and with moderate to high stereoselectivities. In the

• -substituent of unsaturated 1,4-diketone 1 on the reaction was investigated (Table 3). Electron-withdrawing groups, such as bromo and nitro, (Table 3, entries 10 and 13) as well as the electron-donating methoxy group (Table 3, entry 7) led to an increase in stereoselectivity, but the reaction time was also

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• % yield of the nitroketone. Two-directional synthesis of diketone 18 in this fashion did not prove to be feasible; however, it was achieved in good yield by Michael addition of the nitroketone anion to phenylvinylketone. Subjecting diketone 18 to H2 gas and Raney-nickel then reduced the nitro group and

Catalyst-free and solvent-free Michael addition of 1,3-dicarbonyl compounds to nitroalkenes by a grinding method

• Zong-Bo Xie,
• Na Wang,
• Ming-Yu Wu,
• Ting He,
• Zhang-Gao Le and
• Xiao-Qi Yu

Beilstein J. Org. Chem. 2012, 8, 534–538, doi:10.3762/bjoc.8.61

• method. Herein, we report a green protocol for the Michael addition of 1,3-dicarbonyl compounds to nitroalkenes under catalyst- and solvent-free conditions (Scheme 1). Utilizing this simple, rapid, low-cost and effective procedure, various nitro diketone derivatives were synthesized in high yields

Branching out at C-2 of septanosides. Synthesis of 2-deoxy-2-C-alkyl/aryl septanosides from a bromo-oxepine

• Supriya Dey and
• Narayanaswamy Jayaraman

Beilstein J. Org. Chem. 2012, 8, 522–527, doi:10.3762/bjoc.8.59

• methodology include the formation of vinyl halide, vinyl ether, diketone and diol intermediates, which are potential sites for varied types of functionalizations. While exploring such features, we undertook the preparation of septanoside derivatives that are branched out at C-2, so as to afford 2-deoxy-2-C

• oxygen at C-2 of oxyglycal I was retained throughout until the septanoside V was obtained. More importantly, vinyl halide III and diketone IV also form as intermediates of the reaction and these intermediates provide an avenue to expand the scope of the reaction sequence. In the present work, we

Syntheses and applications of furanyl-functionalised 2,2’:6’,2’’-terpyridines

• Jérôme Husson and
• Michael Knorr

Beilstein J. Org. Chem. 2012, 8, 379–389, doi:10.3762/bjoc.8.41

• synthesis starts with 6-carboxy-2-acetylpyridine (20), which is reacted with furfural (1), thus providing chalcone 21. This is then reacted with di-pyridinium salt 22 in the presence of ammonium acetate to afford quinquepyridine 23 (Scheme 4). Another possibility to access the key intermediate “1,5-diketone

• . Nevertheless, it was demonstrated that also asymmetric tpys are accessible via the 1,5-diketone pathway [31]. Michael addition of ethyl picolinoylacetate 29 to chalcone 30 affords diketone 31 in 60% yield. Reaction with ammonium acetate to effect ring closure did not yield a terpyridine, but instead

Synthesis and photooxidation of styrene copolymer bearing camphorquinone pendant groups

• Branislav Husár,
• Norbert Moszner and
• Ivan Lukáč

Beilstein J. Org. Chem. 2012, 8, 337–343, doi:10.3762/bjoc.8.37

• formed in irradiated films of styrene copolymers with pendant BZ groups leads to crosslinking, only small molecular-weight changes in irradiated MCQ/S were observed. Keywords: camphorquinone; 1,2-diketone; (±)-10-methacryloyloxycamphorquinone; photooxidation; polystyrene; Introduction Camphorquinone

Sexithiophenes as efficient luminescence quenchers of quantum dots

• Christopher R. Mason,
• Yang Li,
• Paul O’Brien,
• Neil J. Findlay and
• Peter J. Skabara

Beilstein J. Org. Chem. 2011, 7, 1722–1731, doi:10.3762/bjoc.7.202

• ]dithiole-2-one (C) [30] To a solution of the diketone B (9.5 g, 26.8 mmol) in dichloromethane/glacial acetic acid (3:1 v/v, 200 mL), was added mercuric acetate (11.98 g, 37.6 mmol). The mixture was stirred at room temperature for 16 h and filtered through a silica plug (eluting with dichloromethane). The

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• as the sole product. The aldehyde underwent tandem addition of the anion of simple phthalide (a model for 20; prepared from the parent compound by deprotonation with LDA) and dehydration via mesylate 26 to provide 27, which upon reaction with EtOLi (EtOH + BuLi) in THF rearranged to diketone 28

• to 33 was complicated by the unexpected propensity of the diketone to react with atmospheric oxygen to form the corresponding 2-hydroxy derivative 34. This transformation was virtually instantaneous when the anion of 33 was exposed to the atmosphere, whereas 33 itself was completely hydroxylated in

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• reaction of the benzylic chloride 25 with zinc dust (1.5 equiv) and LiCl (1.5 equiv) in THF at 25 °C for 3.5 h provides the corresponding zinc reagent 26 in 68% yield. Its half-life at 25 °C is approximately two days. The copper(I)-mediated acylation of 26 provides the expected diketone 27 in 74% yield

• ketone are readily tolerated. Thus, the Boc-substituted benzophenone 130 reacts with TMP2Mg·2LiCl (1.1 equiv, −20 °C, 4 h) providing the expected aryl magnesium amide 131, which after a copper-mediated benzoylation leads to the 1,2,3-trisubstituted diketone 132 in 72% yield. This reagent allows a smooth

Continuous gas/liquid–liquid/liquid flow synthesis of 4-fluoropyrazole derivatives by selective direct fluorination

• Jessica R. Breen,
• Graham Sandford,
• Dmitrii S. Yufit,
• Judith A. K. Howard,
• Jonathan Fray and
• Bhairavi Patel

Beilstein J. Org. Chem. 2011, 7, 1048–1054, doi:10.3762/bjoc.7.120

• Research & Development, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK 10.3762/bjoc.7.120 Abstract 4-Fluoropyrazole systems may be prepared by a single, sequential telescoped two-step continuous gas/liquid–liquid/liquid flow process from diketone, fluorine gas and hydrazine starting materials. Keywords

• /liquid–liquid/liquid synthesis of fluoropyrazoles from fluorine, hydrazine and diketone starting materials was constructed from nickel metal and narrow bore PTFE tubing as described previously [28][29] (Figure 1). Briefly, fluorine gas, diluted to 10% v/v solution in nitrogen was added via a mass flow

• controller to the microchannel through Input A, the diketone substrate dissolved in acetonitrile was added by a syringe pump into the microchannel via Input B and was made to react with fluorine while both these starting materials passed down the reactor channel in a ‘pipe flow’ regime, as observed in

Functionalization of anthracene: A selective route to brominated 1,4-anthraquinones

• Kiymet Berkil Akar,
• Osman Cakmak,
• Orhan Büyükgüngör and
• Ertan Sahin

Beilstein J. Org. Chem. 2011, 7, 1036–1045, doi:10.3762/bjoc.7.118

• stereochemistry. For example, although both hydroxy compounds obtained from hexabromides 2 and 3 [1] afforded epoxides 4 and 5 upon treatment with sodium methoxide (Scheme 1, Scheme 5), dihydroxy compound 17 produced olefinic compound 27, whose oxidation gave diketone 28. We also observed different reactivities

Toward an integrated route to the vernonia allenes and related sesquiterpenoids

• Da Xu,
• Michael A. Drahl and
• Lawrence J. Williams

Beilstein J. Org. Chem. 2011, 7, 937–943, doi:10.3762/bjoc.7.104

• prepare 24 by a direct and modular route. Scheme 3 depicts a concise route to 24 and 25. Beginning with the commercially available diketone 18, acid promoted Michael addition with acrolein gave aldehyde 19. A two step procedure, via 20, was employed to obtain the (Z)-bromoolefin 21. Initially, we examined

• -olefination products from diketone aldehyde 19. Computed torsion angles for potential C–C fragmentation substrates.a Supporting Information Supporting Information File 130: General experimental methods and analytical data, 1H and 13C NMR spectra of compounds 18–25 and computed structural coordinates for

Gold-catalyzed oxidation of arylallenes: Synthesis of quinoxalines and benzimidazoles

• Dong-Mei Cui,
• Dan-Wen Zhuang,
• Ying Chen and
• Chen Zhang

Beilstein J. Org. Chem. 2011, 7, 860–865, doi:10.3762/bjoc.7.98

• explorations focused on the reaction of 4-butylphenylallene (1a) (0.5 mmol) in the presence of a catalytic mixture of (Ph3P)AuCl (2 mol %), AgBF4 (8 mol %), and H2SO4 (0.5 mol %) in dioxane (1.0 mL) and water (10 mmol), at 60 °C for 24 h in air. This proceeded efficiently to form a 44:56 mixture of α-diketone

• -withdrawing fluoro or bromo substituent on the benzene ring also took place smoothly (Table 2, entries 5 and 6). Disubstituted allenes were also examined. Thus, the 1,3-disubstituted allene 1g, was oxidized to afford α-diketone 2g and aldehyde 3c in 35% and 32% yields, respectively (Table 2, entry 7

• oxidative transformation under the same reaction conditions. Having prepared a variety of α-diketones and aldehydes successfully, we then undertook the synthesis of quinoxalines and benzimidazoles (Scheme 2). Thus, the treatment of the corresponding mixture of α-diketone 2 and aldehyde 3 with benzene-1,2

A racemic formal total synthesis of clavukerin A using gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes as the key strategy

• Jae Youp Cheong and
• Young Ho Rhee

Beilstein J. Org. Chem. 2011, 7, 740–743, doi:10.3762/bjoc.7.84

• in the formal synthesis of clavukerin A was explored. We first investigated the cyclization–hydrogenation strategy (path A in Scheme 4). Deprotection of 4 and the aldol condensation of the resulting diketone under basic conditions proceeded smoothly to give the enone 2 in good yield. However

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• might exist. One of the key intermediates in the catalytic cycle is the hydrolyzed product – the alkynyl ketone from hydrolysis of one triple bond – which is the same as the substrate that was employed by Yamamoto and co-workers. Thus, a similar diketone intermediate 6' could also have been formed

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• synthetic approach was based on the classical Paal–Knorr cyclocondensation of a highly substituted 1,4-diketone with a primary amine bearing a masked aldehyde functionality. The 1,4-diketone component, which can be accessed via a 3-step sequence [5] starting from aniline, was refluxed with 3

• acceptor obtained from an initial Knoevenagel condensation (Scheme 5). In order to improve the overall yield as well as the convergency, the industrial route [7] introduced the fully elaborated side chain 34 by condensation with the previously described 1,4-diketone 31 (Scheme 5 and Scheme 6). The desired

Reciprocal polyhedra and the Euler relationship: cage hydrocarbons, C_nH_n and closo-boranes [B_xH_x]²⁻

• Michael J. McGlinchey and
• Henning Hopf

Beilstein J. Org. Chem. 2011, 7, 222–233, doi:10.3762/bjoc.7.30

• the mono-protected diketone 28, itself available via photolysis of 27, the mono-ketal of the Diels–Alder dimer of 2-bromocyclopentadienone. At this point, the bishomocubanedione system is exquisitely poised to undergo successive Favorskii reactions to yield eventually the carboxylic acid 29, which

• reaction to prepare the C14 diketone 60 (Scheme 11). In principle, one could incorporate bridgehead halogens as in 61 with the aim of carrying out two Favorskii ring contractions to generate the octahedrane skeleton, viz. the dicarboxylic acid 62, which ultimately would then require to be decarboxylated to

• diketone 65 [36]. We await further elaboration of this fascinating system. Decahedrane, C16H16, 14 Formally, 14 should be available by capping [4]peristylane with a four-membered ring system, as in 66 (Figure 6). However, to translate this concept into a preparatively realistic protocol is a different

Photocycloaddition of aromatic and aliphatic aldehydes to isoxazoles: Cycloaddition reactivity and stability studies

• Axel G. Griesbeck,
• Marco Franke,
• Jörg Neudörfl and
• Hidehiro Kotaka

Beilstein J. Org. Chem. 2011, 7, 127–134, doi:10.3762/bjoc.7.18

• of aci-nitroethane 1 (Scheme 1). The reaction of acetylacetaldehyde with hydroxylamine gave 7b, exclusively. 3,5-Diphenylisoxazole (7f) was prepared from acetophenone and methyl benzoate, followed by cyclization of the resulting diketone 4 with hydroxylamine. 5-Methoxy-3-phenylisoxazole (7g) and 5

Syntheses and properties of thienyl-substituted dithienophenazines

• Annemarie Meyer,
• Eva Sigmund,
• Friedhelm Luppertz,
• Gregor Schnakenburg,
• Immanuel Gadaczek,
• Thomas Bredow,
• Stefan-S. Jester and
• Sigurd Höger

Beilstein J. Org. Chem. 2010, 6, 1180–1187, doi:10.3762/bjoc.6.135

• quantitative yield [21][22]. The respective regio isomer 8 was synthesized starting from commercially available 3-bromothiophene 1 and boronic acid 5 in three steps (Scheme 2). By Suzuki–Miyaura coupling we obtained 3,3’-bithiophene in good yields. The red diketone 7 was prepared by two-fold acylation with