Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

• Zachary Lee,
• Brandon R. Jones,
• Nyochembeng Nkengbeza,
• Michael Phillips,
• Kayla Valentine,
• Alexis Stewart,
• Brandon Sellers,
• Nicholas Shuber and
• Karelle S. Aiken

Beilstein J. Org. Chem. 2019, 15, 2747–2752, doi:10.3762/bjoc.15.265

• -endo-dig cyclization would result in diketone 18. Significantly, the iodine-mediated hydration of all substrates 11 that were studied gave rise to one type of product, 15 (Scheme 3). This indicated that the reaction with alkyl-capped, internal alkynes occurred exclusively through the 5-exo-dig route, a

Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses

• Anne-Marie Caminade,
• Artem Zibarov,
• Eduardo Cueto Diaz,
• Aurélien Hameau,
• Maxime Klausen,
• Kathleen Moineau-Chane Ching,
• Jean-Pierre Majoral,
• Jean-Baptiste Verlhac,
• Olivier Mongin and
• Mireille Blanchard-Desce

Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221

• derivatives grafted on the surface of phosphorhydrazone dendrimers. In this case, a β-diketone functionalized by a phenol was first grafted on the surface of the dendrimer [47], then BF3 was added to obtain the dioxaborines (Scheme 3). Monomer, dimer, and all generations of the dendrimer from zero (6 terminal

Superelectrophilic carbocations: preparation and reactions of a substrate with six ionizable groups

• Sean H. Kennedy,
• Makafui Gasonoo and
• Douglas A. Klumpp

Beilstein J. Org. Chem. 2019, 15, 1515–1520, doi:10.3762/bjoc.15.153

• benzaldehyde. A nickel-catalyzed procedure gives the dipyridyl intermediate 7 [13]. This is easily oxidized to the diketone 8 and reaction of this substance with 2-lithiopyridine gives the precursor 9. The diol 9 is a substrate with six ionizable groups. Upon ionization in superacidic CF3SO3H (triflic acid

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• start with the formation of an imine intermediate between the aldehyde function of 33 and the amine 2, followed by a nucleophilic attack by the diketone and a final intramolecular cyclization, the Han group proposes a different pathway, with an initial deprotonation of ketoacid 34 (R2 = Me, Ar, R3 = OH

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• OX17. This sequence demonstrates the potential of the C-5 functionalized oxazoles to be used for further transformations (see below). The examples collected in Table 6 show a dichotomy of oxazole and 1,2-diketone formation that is not fully understood so far. As mentioned above, the presence of bulky

• substituents R2 (and R3) seems to be a prerequisite of the 1,2-diketone formation, however, for the series with R2 = phenyl the observed product distributions are not easy to explain (Table 6, entries 18–23). Nevertheless, a plausible mechanism is presented in Scheme 24 showing the analogy to the Gabriel

• alternative to the strongly acidic conditions, palladium-catalyzed hydrogenolysis of the benzyloxy-substituted derivatives is possible, thus avoiding the condensation to oxazoles. Scheme 25 shows the conversion of KE52 into 1,2-diketone DK14 (compare entry 3 of Table 6). Longer reaction times lead to a

A convenient and practical synthesis of β-diketones bearing linear perfluorinated alkyl groups and a 2-thienyl moiety

• Ilya V. Taydakov,
• Yuliya M. Kreshchenova and
• Ekaterina P. Dolotova

Beilstein J. Org. Chem. 2018, 14, 3106–3111, doi:10.3762/bjoc.14.290

• -diketone 3b is known and the staring material is readily available. All the experiments were performed using about 5 mmol of compounds. The ratio of reagents was 1:1 (ketone to ester), while from 1 up to 2.5 equivalents of a base were applied. The order of reagent mixing is also significant. It was found

• that mixing 2-acetylthiophene with a base in the absence of the ester (var. A) should be avoided due to notable darkening and self-condensation of the ketone, despite Prabhu’s recommendations [25]. Similar yields of a β-diketone were obtained if the ester of perfluorocarboxylic acid was first added to

• evaporator, 60 °C, 5 Torr). The residue was pulverized in dry Ar atmosphere and dried at 0.05 Torr and 60 °C for at least 5 h. The quality of the alkoxide dramatically affects the yields of a β-diketone, while the stoichiometry is much less significant. The best results were achieved with commercial NaOMe or

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• selenium dioxide in boiling ethanol, followed by dehydrogenation with bromine in acetic acid at 100 °C. Another method for the synthesis of 7-hydroxy-2,3-benzotropone (241) starting from the reaction of diketone 276 with boiling acetic anhydride was achieved by Maignan (Scheme 44) [168]. The reaction of

• were catalyzed by NaOH. 5.4.2. Reaction of 4-hydroxy-2,3-benzotropone (174): The structure of 174 was confirmed by the reduction of both benzotropolone 174 and diketone 300 into the diol 305 with catalytic hydrogenation (Scheme 51) [178]. 6. Halobenzotropones 6.1. Monohalobenzotropones 6.1.1. One-step

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• Keshaba N. Parida Gulab K. Pathe Shimon Maksymenko Alex M. Szpilman Department of Chemical Sciences, Ariel University, 4070000 Ariel, Israel 10.3762/bjoc.14.84 Abstract Due to their closely matched reactivity, the coupling of two dissimilar ketone enolates to form a 1,4-diketone remains a

• of enolates may be used to form the 1,4-diketone products in 38 to 74% yield. Due to the use of two TMS enol ethers as precursors, an optimization of the cross-coupling should include investigating the order of addition. Keywords: 1,4-diketones; enolates; enolonium species; hypervalent iodine

• = H) to afford the 1,4-diketone 7 in 71% yield (Scheme 2) [31]. We therefore focused on identifying the minimum amount of the second enolate that would lead to optimal yields and found that as little as 1.2–1.4 equiv provided the desired 1,4-diketones in acceptable yields without the need for a large

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• acetic acid (Scheme 1). In the same report the other regioisomers 6-trifluoromethylpyrazolo[3,4-b]pyridines 20 were obtained under multicomponent solvent-free conditions by the reaction of hydrazine 14, β-ketonitrile 15 and β-diketone 17 as an exclusive product. The structures of both the regioisomers

• have been confirmed unambiguously by HMBC, HMQC and 19F NMR studies. The authors proposed that trifluoromethyl-β-diketone exists mainly in keto form 17 under solvent-free conditions whereas under solvent-mediated conditions the enolic form 21 towards the carbonyl carbon that carries the CF3 group is

• [2,3-e]pyrazolo[3,4-b]pyridine 77 was formed in the reaction when indandione 58 was used as β-diketone which was attributed to the loss of the benzyl fragment from 5-aminopyrazole derivative 75. Microwave-assisted reactions went to completion in very short time (5 min) compared to reactions under

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• ) while good yields were obtained with β-ketoesters containing n-propyl and n-butyl moieties (Scheme 2, 3r and 3s). However, significantly lower yields were obtained with the sterically more demanding iPr group (Scheme 2, 3t). Unfortunately, β-diketone (acetylacetone) was not suitable for the reaction as

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• selective benzylation of its equatorial hydroxy group [14] followed by chlorochromate oxidation gave, after removal of the benzyl protecting group in 26, the diketone 27. Its reduction proceeded regio- and stereoselectively to afford the 2α,3β-diol 28. Finally, treatment of this compound with KOH in MeOH

• agent used. Thus, the reaction of 3,6-diketones with K-selectride was shown to afford 3α-hydroxy-6-ketones [31]. On the other hand, treatment of the diketone 31 with NaBH4 followed by acetate deprotection led to 24-epiteasterone (34) having a 3β-hydroxy group on the A-ring (Scheme 7). 2α-Hydroxy-3

Curcuminoid–BF₂ complexes: Synthesis, fluorescence and optimization of BF₂ group cleavage

• Henning Weiss,
• Jeannine Reichel,
• Helmar Görls,
• Kilian Rolf Anton Schneider,
• Mathias Micheel,
• Michael Pröhl,
• Michael Gottschaldt,
• Benjamin Dietzek and
• Wolfgang Weigand

Beilstein J. Org. Chem. 2017, 13, 2264–2272, doi:10.3762/bjoc.13.223

• avoid a Knoevenagel condensation at the C-3 atom (Scheme 1a), the β-diketone moiety needs to be fixed into the enol form. In principle, this can be achieved by two different methods. The first one described by Pabon et al. utilises boric oxide in ethyl acetate as an intermediate agent (Scheme 1a) [8

• attention regarding their properties as fluorescent dyes with fluorescence quantum yields of up to 60% and Stokes shifts of up to 5000 cm−1 [9]. Additionally, the incorporation of the BF2 group forces the β-diketone unit into the enol form, which leads to increased rigidity and enhanced photostability of

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• hydrolysis of the oximino group gave target steroid 25 with the desired configuration of all stereogenic centers. In the attempted route to (+/−)-isocomene, Oppolzer and co-workers suggested pentalenone 29, accessible by an intramolecular aldol condensation/elimination of diketone 30, as a key precursor

• . Diketone 30 was prepared in a straightforward manner by C-C-coupling of nitrosoalkene NSA7 (generated in situ from the corresponding α-bromooxime 31) with silyl enolate of 2-methylcyclopentanone, and subsequent deoxygenation of the resulting oxime 32 with CAN. Unfortunately, attempts to convert pentalenone

The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy

• Patrick A. Julien,
• Ivani Malvestiti and
• Tomislav Friščić

Beilstein J. Org. Chem. 2017, 13, 2160–2168, doi:10.3762/bjoc.13.216

• organic transformation, the previously reported mechanochemical condensation of a diketone and a diamine to form an N-heteroacene [40]. We have utilized an in-house built setup for real-time Raman spectroscopy monitoring of the synthesis of 2,3-diphenylquinoxaline from benzil and o-phenylenediamine

NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones

• Ken Takaki,
• Makoto Hino,
• Akira Ohno,
• Kimihiro Komeyama,
• Hiroto Yoshida and
• Hiroshi Fukuoka

Beilstein J. Org. Chem. 2017, 13, 1816–1822, doi:10.3762/bjoc.13.176

• recently obtained by the dimsyl anion-promoted double acylation of enones with benzils, followed by dehydrogenation of the resulting alkanes in one pot [16]. Moreover, if the reaction of cyclic 1,2-diketone I (G = C(O)R1) with activated alkenes may take place similarly, this reaction could be utilized as a

• NHC followed by migration of one neighboring acyl group to the central carbonyl oxygen would generate bisacylated Breslow intermediate 10 (Scheme 5). If this species behaves in a similar manner as the monoacylated intermediate C derived from 1,2-diketone 1, its reaction with enone 6a would be expected

α-Acetoxyarone synthesis via iodine-catalyzed and tert-butyl hydroperoxide-mediateded self-intermolecular oxidative coupling of aryl ketones

• Liquan Tan,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2017, 13, 1079–1084, doi:10.3762/bjoc.13.107

• and TBHP [24][25]. An I−/I2 redox cycle promotes tert-butoxyl and tert-butylperoxyl radical formation from TBHP [26][27][28]. In the presence of TBHP and I2, α-iodoaryl ketones 5 and 6 are oxidized to a 1,2-diketone intermediate 7 and an α-carbonyl radical 9, which can be further transformed to tert

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• steric hindrance effect in 2,2,6,6-tetramethyl-3,5-heptanedione 2d displays an important role in the overall reaction and only traces of product 3d was observed (Table 2, entries 1–3 vs 4). Unfortunately, no reaction occurred when cyclic β-diketone 2e was employed as substrate (Table 2, entry 5). We next

• as a mixture of regioisomers (6:1) (Table 2, entry 10). In addition, the possibility to perform the reaction of 2-azidophenyl phenyl selenide (1a) with β-keto-esters, β-keto-amides and α-cyano-ketones 2f–k was also investigated. The reaction conditions optimized for 1,3-diketone 2a were employed, but

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• treatment with p-toluenesulfonic acid in acetone to give the diketone 245 (Scheme 68). Then, the latter underwent oxidative aromatization by treatment with Pd/C in p-cymene. The synthesized 1-indanone 246 was further converted to the cis-1-amino-2-indanol 247 and used as ligand for asymmetric reactions. A

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