Organofluorine chemistry: Difluoromethylene motifs spaced 1,3 to each other imparts facial polarity to a cyclohexane ring

• Mathew J. Jones,
• Ricardo Callejo,
• Alexandra M. Z. Slawin,
• Michael Bühl and
• David O'Hagan

Beilstein J. Org. Chem. 2016, 12, 2823–2827, doi:10.3762/bjoc.12.281

• relationship. Results and Discussion The preparation of diketones 5a–c and bis-dithianes 6a–c was carried out by previously described methods. The dimethyl-diketone 5c was prepared by double methylation of 5b [25] (Scheme 2). Two different O-alkylated products 7 and 8 were also obtained as significant

• byproducts. The reaction of ketones 5a–c with 1,2-ethanedithiol in the presence of catalytic BF3·OEt2 afforded the corresponding bis-dithianes 6a–c in moderate to good yields [26] (Scheme 2). The reaction of diketone 5c also afforded the monoderivatised ketone 9 as a minor product. Direct fluorination of

• order to block enolisation, diketone 5c containing two methyl groups α to the ketones was subject to fluorination with DAST and Deoxo-Fluor®. In this case the reaction was successful and the desired tetrafluorocyclohexane 4c could be obtained, most preferably with DAST although in a low overall yield

Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification

• Anna Zaghi,
• Daniele Ragno,
• Graziano Di Carmine,
• Carmela De Risi,
• Olga Bortolini,
• Pier Paolo Giovannini,
• Giancarlo Fantin and
• Alessandro Massi

Beilstein J. Org. Chem. 2016, 12, 2719–2730, doi:10.3762/bjoc.12.268

• (DMF) solvent to the α-diketone and generate the corresponding enediolate active species. After having identified the 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine on polystyrene (PS-BEMP) as the suitable base, packed-bed microreactors (pressure-resistant stainless-steel

• ). Keywords: C–C coupling; continuos-flow; diketone; electron-transfer; umpolung; Introduction The polarity reversal (umpolung) of carbonyl compounds by N-heterocyclic carbene (NHC) or cyanide catalysis represents a straightforward strategy for the synthesis of valuable molecules such as, among the many

• use of a readily and commercially available supported base as packing material of fixed-bed microreactors. The present study originated from our recent findings on a novel strategy for the umpolung of aromatic α-diketone donors [26] and their peculiar reactivity with aromatic aldehydes or α,β

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

• -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

Synthesis and properties of fluorescent 4′-azulenyl-functionalized 2,2′:6′,2″-terpyridines

• Adrian E. Ion,
• Liliana Cristian,
• Mariana Voicescu,
• Masroor Bangesh,
• Augustin M. Madalan,
• Daniela Bala,
• Constantin Mihailciuc and
• Simona Nica

Beilstein J. Org. Chem. 2016, 12, 1812–1825, doi:10.3762/bjoc.12.171

• isolate this intermediate failed. The compound is very unstable and it decomposes very rapidly, both in solid and in solution. In accordance with previous reports [23][27] and with ESIMS analysis [28], we hypothesized that this corresponds to a diketone structure. This raw, freshly prepared compound is

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• -dioxolanes 151 are rearranged similarly to the Criegee mechanism into diketone derivatives 152 (Scheme 44) [298]. Unlike the Baeyer–Villiger rearrangement, in which only mono-O-insertion can take place, the Criegee rearrangement of peroxide 153 in an acidic medium and under solvent-free conditions does not

• activities, including antibacterial, antiviral, antifungal, anti-allergic, anti-oxidant, and anti-inflammatory [348][349]. The treatment of endoperoxide 238 with Et3N gave 1,4-diketone 240 in quantitative yield instead of expected hydroxy ketone 239 (Scheme 73) [350][351][352]. The endoperoxide 238 is

• presumably converted into hemiketal 241, which is rearranged in several steps into diketone 240 (Scheme 74) [351]. The reaction of endoperoxide 242a containing an electron-donating substituent at the double bond with bases results in the rearrangement product diketone 243. Under the same conditions, the base

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• review, Lou and co-workers reported an additional example of conjugate addition–enantioselective protonation involving an α,β-unsaturated ketone. In the new report, a chiral primary amine catalyzed conjugate addition of a 1,3-diketone nucleophile into an in situ generated ortho-quinone methide was

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• couplings. Thus, a library of specifically substituted bipyridine derivatives was generated, showing the versatility of the simple 1,3-diketone-based approach to this important class of ligands. Keywords: 2,2-bipyridines; cross couplings; cyclocondensation; β-ketoenamides; nonaflates; Introduction In 2009

• -phenylpropan-2-one (76% yield) was observed instead. For the amination of benzyl-substituted diketone 1d both of the above utilized methods failed to provide the desired compound 2d. While treatment with ammonium formate exclusively leads to deacetylation of the starting material to 4-phenylbutan-2-one, the

Iodine-mediated synthesis of 3-acylbenzothiadiazine 1,1-dioxides

• Long-Yi Xi,
• Ruo-Yi Zhang,
• Lei Shi,
• Shan-Yong Chen and
• Xiao-Qi Yu

Beilstein J. Org. Chem. 2016, 12, 1072–1078, doi:10.3762/bjoc.12.101

• alknyl group were subjected to this reaction, besides the formation of 3-acylbenzothiadiazine 1,1,-dioxide skeletons, the triple bond was further transformed into an ortho-diketone functionality (Scheme 4) [27][28][29]. 1,2-Dicarbonyl functionalities are one of the most important skeletons found in

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• observed yielding several products (Scheme 3). Since the cyclic hemiacetal structure (of a diketone) represents the only functional difference to the other flavanonols employed, it is obviously unstable under the conditions used. Conclusion To our knowledge, this is the first semi-synthesis of optically

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• good yield and stereoselectivity, given the high molecular complexity that is being achieved in one step (Scheme 64). The researchers suggested that diketone 204 and benzaldehyde 205 reacts through Knoevenagel condensation, to produce 2-arylidene-1,3-indanediones, which is subsequently attacked by the

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• for the asymmetric synthesis of functionalised cyclopentanones was disclosed in 2009 by Rovis. The chiral secondary amine 60 catalyzes the initial asymmetric Michael addition of an 1,3-diketone and an enal to afford a δ-ketoaldehyde 61. Subsequently, a cross-benzoin reaction of the latter promoted by

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• coraxeniolide A (10) [12], starting from chiral (−)-Hajos–Parrish diketone (58) [39]. Based on Pfander's seminal work, the first total synthesis of a xenicane diterpenoid was then accomplished by Leumann in 2000 (Scheme 6) [40]. Starting from enantiopure (−)-Hajos–Parrish diketone (58), allylic alcohol 59 was

• overall yield of 1.7%. The total syntheses of coraxeniolide A (10) and β-caryophyllene (22) reported by Corey [46] in 2008 are based on Pfander’s idea [24] to construct the cyclononene fragment from (−)-Hajos–Parrish diketone (58) [39] (Scheme 8). Chiral hydroxy dione 77 was synthesized according to a

• oxolane bridge between C1 and C7. Hajos–Parrish diketone (107) [39] served as the starting material for the preparation of key intermediate 112. Selective reduction of the ketone and silylation of the resulting alcohol furnished enone 108. α-Carboxylation of the enone with magnesium methyl carbonate and a

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• -workers [71] successfully achieved the selective mono-α-chlorination of β-keto esters/amides and 1,3-diketone 78 by employing an electrochemical synthesis via a catalysis by means of Cu(OTf)2. The synthesis of chlorinated carbonyl products 79 were acquired in a divided cell using aqueous HCl as chlorine

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• -azidochalcone 1a (R1 = 4-Br, R2 = 4-OMe) with trifluoroacetic acid under microwave conditions [33] at 100 °C for 2 minutes to obtain diketone 3a (79%) as a solid without any side products (Scheme 1). The 1H NMR spectrum of 3a exhibits a methine proton doublet at 6.78 ppm. In the 13C NMR spectrum, two carbonyl

• carbon signals and an amide carbon signal appear at 190.6, 188.8, and 165.1 ppm, respectively. In addition, a methine carbon signal appears at 60.4 ppm. The structural confirmation of α-amido-1,3-diketone 3e by one- and two-dimensional NMR spectroscopic data is depicted (see Supporting Information File 1

• various substituted benzoic acids 2d–g as well and the resultant α-amido-1,3-diketones 3k–o are obtained in moderate to good yields (Figure 3). The mechanism for the formation of α-amido-1,3-diketone 3 is given in Scheme 2. Initially, by thermolysis, α-azidochalcone undergoes denitrogenative decomposition

Polythiophene and oligothiophene systems modified by TTF electroactive units for organic electronics

• Alexander L. Kanibolotsky,
• Neil J. Findlay and
• Peter J. Skabara

Beilstein J. Org. Chem. 2015, 11, 1749–1766, doi:10.3762/bjoc.11.191

• 4,6-diaryl substituted thienodithiole-2-ones, e.g., 4,6-di(thiophen-2-yl)thieno[3,4-d][1,3]dithiol-2-one (15c), construction of the thiophene directly onto the dithiole ring seems to be the only strategy, which can be readily achieved by reductive cyclisation of diketone 22 [60] (synthetic pathway B

• reaction, is unstable and undergoes various rearrangments [68][69] in acidic conditions. Hence, it is preferably oxidised directly to the more stable diketone 25c without delay. The retrosynthetic scheme for the monomer units 28a,b with thieno-dithiino-dithiole type fusion is shown in Scheme 7. Similar to

• the aforementioned synthetic pathway B, the strategy for the synthesis of 29 involves construction of the thiophene ring by cyclisation of diketone 30 (synthetic pathway C). The diketone 31 is constructed through the cycloaddition reaction of diacylethene 33 with oligomer 32, readily available by

Design and synthesis of hybrid cyclophanes containing thiophene and indole units via Grignard reaction, Fischer indolization and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Mukesh E. Shirbhate

Beilstein J. Org. Chem. 2015, 11, 1514–1519, doi:10.3762/bjoc.11.165

• Vilsmeier–Haack reaction starting with the thiophene [33]. Later, diol 6 was oxidized with MnO2 [34] to deliver diketone 3. Our attempts to realize the RCM product 2 with dione 3 via a reaction with Grubbs’ catalyst failed to give the expected cyclized product. In most instances, we observed the degradation

• , diketone 3 was subjected to a double Fischer indolization with 1-methyl-1-phenylhydrazine under conditions of a low melting reaction mixture to generate the bisindole derivative 5. It is interesting to note that conventional conditions (AcOH/HCl) for Fischer indolization were not successful with systems

• of a mixture of L-(+)-tartaric acid/N,N′-dimethylurea (30:70) was heated to 70 °C to obtain a clear melt. To this melt, 2 mmol of N-methyl-N-phenylhydrazine and 1 mmol of diketone were added at 70 °C. After completion of the reaction (TLC monitoring by mini work up), the reaction mixture was quenched

Spiro annulation of cage polycycles via Grignard reaction and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Mohammad Saifuddin,
• Rashid Ali and
• Gaddamedi Sreevani

Beilstein J. Org. Chem. 2015, 11, 1367–1372, doi:10.3762/bjoc.11.147

• polymeric components. However, the home-made Grignard reagent at low concentration (0.1 M solution) exists mostly in the monomeric form. So, we speculate that the difference in the concentration may be responsible for the formation of diol 11 [49][50][51]. Alternatively, when the diketone was reacted with

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• reported the synthesis of [11](2,6)-pyridinophane (37), a normuscopyridine analogue, by an oxymercuration–oxidation strategy. The ketoolefin 34 was converted to the hydroxyketone 35 by treatment with Hg(OAc)2 and NaSH. Oxidation of the keto alcohol 35 gave diketone 36, which reacted with hydroxylamine

• key building block for the synthesis of calix[4]arene. Here, α,ω-bis(p-methoxyphenyl)alkanes 264 were used as starting materials. Compound 264 was treated with acetic anhydride and AlCl3 in nitrobenzene and 1,1,2,2-tetrachloroethane to generate diketone 265 in 58–93% yield. Diketone 265 was then

Design and synthesis of fused polycycles via Diels–Alder reaction and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha and
• Ongolu Ravikumar

Beilstein J. Org. Chem. 2015, 11, 1259–1264, doi:10.3762/bjoc.11.140

• , and multiplet, respectively. Coupling constants (J) are reported in Hertz. Experimental procedures Synthesis of compound 4 Analogously as described in [2], to a stirred solution of diketone 3 (0.2 g, 0.83 mmol) in dry THF (10 mL) was added allylmagnesium bromide (4.2 mL, 1 M solution in ether) at 0 °C

• , CDCl3) δ 135.5, 134.7, 134.4, 118.3, 73.4, 52.3, 52.3, 50.6, 49.2, 45.8, 45.7, 44.8 ppm; HRMS (Q–ToF) m/z: [M + Na]+ calcd for C17H20ONa, 347.1982; found, 347.1980. Synthesis of compound 9 Analogously as described in [2], to a stirred solution of diketone 8 (0.5 g, 1.8 mmol) in dry THF (10 mL) was added

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• . To determine whether the protection of the alkyne group was necessary for a rearrangement to take place, the reaction was carried out on compound 27. In the presence of perrhenic acid, 16% of the starting material was recovered along with 36% of diketone 28 (Scheme 6). No cyclization product was

Bis(vinylenedithio)tetrathiafulvalene analogues of BEDT-TTF

• Erdal Ertas,
• İlknur Demirtas and
• Turan Ozturk

Beilstein J. Org. Chem. 2015, 11, 403–415, doi:10.3762/bjoc.11.46

• molecules, obtained from 1,8-diketone ring closure reactions, and coupling reactions, published by our group. Review BVDT-TTF analogues from 1,8-diketones Bis(vinylenedithio)tetrathiafulvalene (BVDT-TTF) 4 (R = Ph, 4-CH3OC6H4, 4-BrC6H4, 4-CH3C6H4, 4-O2NC6H4, 2-thienyl) is a fully unsaturated analogue of

• BEDT-TTF (ET) 3. It possesses a vinyl moiety at the peripheries in place of the ethylene group of ET. It can also be considered as a tetrathiafulvalene analogue having fused 1,4-dithiin rings as its peripheries. The synthesis was achieved through the reaction of a 1,8-diketone with Lawesson’s reagent

• of synthesizing fused 1,4-dithiin and thiophene ring systems, possessing functional groups such as Ph 4-MeOC6H4 and 4-O2NC6H4 (Scheme 1) [46]. The synthesis involved treatment of the diketone 6, produced through the reaction of the readily available dianion 5 [52] with α-haloketones, with Lawesson’s

Attempts to prepare an all-carbon indigoid system

• Şeref Yildizhan,
• Henning Hopf and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 363–372, doi:10.3762/bjoc.11.42

• that caused all these preparative difficulties, we next decided to investigate the behavior of diketone 19, in which this conjugation is interrupted. Although its methylenation under Wittig conditions was again unsuccessful, the reaction with the Tebbe’s reagent provided a product. This, however, was

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• was crossed with methyl vinyl ketone in 62% yield [34]. Reduction of enone 34 was achieved in the presence of Pd/C with H2 in EtOAc to furnish diketone 35 [34]. Chemoselective Wittig mono-olefination of 35 provided ω-enone (−)-32, spectroscopically identical to the material in Danishefsky’s racemic

(CF₃CO)₂O/CF₃SO₃H-mediated synthesis of 1,3-diketones from carboxylic acids and aromatic ketones

• JungKeun Kim,
• Elvira Shokova,
• Victor Tafeenko and
• Vladimir Kovalev

Beilstein J. Org. Chem. 2014, 10, 2270–2278, doi:10.3762/bjoc.10.236

• JungKeun Kim Elvira Shokova Victor Tafeenko Vladimir Kovalev Laboratory of Macrocyclic Receptors, Department of Chemistry, Moscow State University, Lenin’s Hills, Moscow 119991, Russia 10.3762/bjoc.10.236 Abstract A very simple and convenient reaction for 1,3-diketone preparation from carboxylic

• the most important class of organic compounds, since they are applied as key structural blocks in organic syntheses, exhibit different kinds of biological activities, and display a broad range of ionophoric properties [1][2][3]. The method most frequently used for 1,3-diketone synthesis is the Claisen

• (2а), which was initially formed as the result of an intramolecular cyclization of 1a, underwent a further acylation with the formation of 1,3-diketone 3a. In contrast, γ-phenylbutanoic acid (1c) was quantitatively transformed only to the tetralone 2с (Table 1, entries 10 and 11). The acid-catalyzed

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• use of 1,3-diketone, 1,3-ketoester and 1,3-diester derivatives in retrosynthetic planning is widespread in general organic chemistry and numerous terpenes, heterocycles and steroids originate from such simple yet synthetically versatile substrates [16][17][18][19]. In contrast, despite the