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

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

• solution polymerization was demonstrated by Qi et al. who were able to polymerize styrene with horseradish peroxidase, hydrogen peroxide, and a β-diketone in aqueous direct miniemulsion [92]. Normally, only hydrophilic monomers can be polymerized with this initiating system in water or a co-solvent, e.g

Synthesis of oxa-bridged derivatives from Diels–Alder bis-adducts of butadiene and 1,2,3,4-tetrahalo-5,5-dimethoxycyclopentadiene

• Faiz Ahmed Khan and
• Karuppasamy Parasuraman

Beilstein J. Org. Chem. 2010, 6, No. 64, doi:10.3762/bjoc.6.64

• yield. Ruthenium catalyzed oxidation of the bis-adducts followed by a one-pot transformation of the resulting α-diketone furnished oxa-bridged compounds. Unambiguous stereochemical assignments of both diastereomeric series are reported. Keywords: Diels–Alder reactions; diketones; oxa-bridged

• analysis (Figure 1) [20]. Working backwards, the structures of the adduct 5, the bis-diketone 7 were confirmed unequivocally. We next turned our attention to the bromo analogue 1b in order to see if the overall yield of the bis-oxa-bridged derivatives 8 and 10 could be improved. We were also interested to

• chloro-analogue furnished mono-adduct 11 (endo:exo = 91:9) and bis-adducts 12 and 13 (Scheme 4). The bis-adducts 12 and 13 were separated by preparative HPLC. The bis-adducts 12 and 13 were converted in excellent yields to the corresponding bis-α-diketones 14 and 15 (Scheme 5). Bis-diketone 14 was

Synthesis of spiroannulated and 3-arylated 1,2,4-trioxanes from mesitylol and methyl 4-hydroxytiglate by photooxygenation and peroxyacetalization

• Axel G. Griesbeck,
• Lars-Oliver Höinck and
• Jörg M. Neudörfl

Beilstein J. Org. Chem. 2010, 6, No. 61, doi:10.3762/bjoc.6.61

• our work on bis-peroxide synthesis from bifunctional ketones [22], we have also studied the peroxyacetalization of the allylic hydroperoxide 7 with the bifunctional cyclohexane-1,4-dione (CHD, Scheme 2). In this case, one equivalent of the diketone gave the monoadduct 9c in 20% yield. The products

An expedient and new synthesis of pyrrolo[1,2-b]pyridazine derivatives

• Rajeshwar Reddy Sagyam,
• Ravinder Buchikonda,
• Jaya Prakash Pitta,
• Himabindu Vurimidi,
• Pratap Reddy Padi and
• Mahesh Reddy Ghanta

Beilstein J. Org. Chem. 2009, 5, No. 66, doi:10.3762/bjoc.5.66

• -methyl-3-oxo-pentanoic acid phenylamide with tertiary butyl carbazate and subsequent condensation of the resulting carbamate derivative with a chalcone provided a facile new approach to pyrrolo[1,2-b]pyridazine derivatives. Keywords: 1,4-diketone; migration and cyclization; pyrrolo[1,2-b]pyridazine

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

Diastereoselective and enantioselective reduction of tetralin- 1,4-dione

• E. Peter Kündig and
• Alvaro Enriquez-Garcia

Beilstein J. Org. Chem. 2008, 4, No. 37, doi:10.3762/bjoc.4.37

• accessible and offers interesting opportunities for synthesis. Results The title reactions were explored. L-Selectride reduced the diketone to give preferentially the cis-diol (d.r. 84 : 16). Red-Al gave preferentially the trans-diol (d.r. 13 : 87). NaBH4, LiAlH4, and BH3 gave lower diastereoselectivities

• ; Introduction In this article, we briefly review synthetic approaches to 2,3-dihydro-1,4-naphthoquinone, more simply named tetralin-1,4-dione (2). This symmetric diketone is the stable tautomer of 1,4-dihydroxynaphthalene (1). Although known for many years, it has never been used in synthesis. The reactions of

• . Using the tautomerization of 1 in trifluoroacetic acid to generate 2 [4], we found that upon solvent evaporation the tautomer obtained was dihydroxynaphthalene 1, rather than diketone 2. During evaporation, the lower solubility of 1 led to its precipitation and this shifted the equilibrium back. This

End game strategies towards the total synthesis of vibsanin E, 3-hydroxyvibsanin E, furanovibsanin A, and 3-O-methylfuranovibsanin A

• Brett D. Schwartz,
• Craig M. Williams and
• Paul V. Bernhardt

Beilstein J. Org. Chem. 2008, 4, No. 34, doi:10.3762/bjoc.4.34

• diketone dehydration (i.e. phosphorus pentaoxide [23]). For Padwa’s protocol the TMS enol ether 33 was required, which was obtained in 75% from sequential treatment of 30 with LDA and TMSCl. Subsequent reaction of 33 with Padwa’s electrophile 34 [24] and silver tetrafluoroborate gave a complex mixture with

• diketone 40, which could be accessed from 43 (and 44) via a Wacker oxidation (64%), also failed to yield furan functionality using classical conditions (i.e. phosphorus pentaoxide and amberlyst resin) (Scheme 6). Enol ester sidechain construction: although Davies [16] has reported the construction of the

• directed towards bis-epi-3-hydroxyvibsanin E 51. This manoeuvre was further justified by the fact that diketone 40 was readily available via the allylation/Wacker protocol as described in Scheme 6. Considering the knowledge gained in Scheme 8, it was perceived best not to perform tricarbonyl reduction then

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• acrylonitrile (88), obtained in turn from 2-alkylcyclopentanedione 89. Diketone 90 was advanced to vinylogous ester 91, the enolate of which was acylated with the Mander reagent to furnish 92 (Scheme 16). The subsequent Michael addition of 92 to acrolein proceeded in quantitative yield under the catalytic

• sordaricin analog 98. In summary, diketone 98 was obtained from starting compound 90 in an overall yield of 19% over 7 steps. The sordarin analogs shown in Scheme 16 exhibit a bridgehead methoxy instead of a carboxy group. Efforts to adapt the general strategy delineated above to the preparation of

Perhalogenated pyrimidine scaffolds. Reactions of 5-chloro- 2,4,6-trifluoropyrimidine with nitrogen centred nucleophiles

• Emma L. Parks,
• Graham Sandford,
• John A. Christopher and
• David D. Miller

Beilstein J. Org. Chem. 2008, 4, No. 22, doi:10.3762/bjoc.4.22

• , many pyrimidine derivatives have been used for various medicinal applications (Figure 1) [1][2][3]. Synthesis of pyrimidine rings most commonly involves cyclocondensation reactions of amidine, guanidine or thiourea derivatives with either 1,3-diketone or 1,3-diester systems [4][5]. However, many of