Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors

• Morgan Hans,
• Jan Lorkowski,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252

• diazabutadiene cleanly precipitated from the reaction mixture and could be isolated in high yield by simple filtration and washing. For the critical cyclization step of IDip*·HCl, Markó et al. ingeniously took advantage of the Lewis acidity of zinc chloride to activate paraformaldehyde and of its coordinating

Photoinduced 1,2,3,4-tetrahydropyridine ring conversions

• Baiba Turovska,
• Henning Lund,
• Viesturs Lūsis,
• Anna Lielpētere,
• Edvards Liepiņš,
• Sergejs Beljakovs,
• Inguna Goba and
• Jānis Stradiņš

Beilstein J. Org. Chem. 2015, 11, 2166–2170, doi:10.3762/bjoc.11.234

• deprotonated efficiently in the presence of superoxide including Hantzsch 1,4-dihydropyridines [31][32]. Cation radicals have increased acidity comparing to the parent molecules from which they are derived by oxidation [33][34][35]. Consequently, their deprotonation proceeds more efficiently. Photooxygenation

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• Pd(TFA)2 catalyzed dehydrogenation on the silyl enol ether 10 and in the presence of Na2HPO4 buffer, in order to mitigate the detrimental acidity of TFA. However, 11 was produced in a modest yield of 21%, because, even at these mild conditions, 10 reconverted to the initial ketone 9 faster than its

Efficient synthesis of π-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp²)–H bond arylations

• Fatiha Abdelmalek,
• Fazia Derridj,
• Safia Djebbar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2015, 11, 2012–2020, doi:10.3762/bjoc.11.218

• )benzofuran (20) only reacted through the activation of the electron-deficient phenyl ring to afford the heteroaryl triad 28 in 56% yield. We imputed this shift of regioselectivity to the high acidity of the C–H bond flanked by the two fluorine atoms. Then, the regioselectivity of Pd-catalyzed second direct

Lewis acid-promoted hydrofluorination of alkynyl sulfides to generate α-fluorovinyl thioethers

• Davide Bello and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 1902–1909, doi:10.3762/bjoc.11.205

• 3HF·Et3N. In light of these observations, our working hypothesis is that the Lewis acid acts to increase the acidity of the 3HF·Et3N by sequestering fluoride ions as relatively unreactive metal fluorides; thus, the alkynyl sulfides are activated by protonation possibly through an intermediate such as A as

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• using the DFT B3LYP method in order to rationalize the experimental results. Keywords: CH acidity; indoles; iodolysis; mixed lithium–zinc bases; pyrroles; Introduction Pyrrole occurs in very important natural products such as tetrapyrrolic (linear) bilirubinoids, and (cyclic) porphyrins and corrins

• , Figure 4, see Supporting Information File 2). Computational aspects There is a lack of data on the acidity of N-substituted pyrroles and indoles in the literature. NH acidity of unsubstituted pyrrole and indole in DMSO was measured by Bordwell [48] and computed by means of semi-empirical AM1 [49] and ab

• recently [42][52]. The results of quantum chemical calculations on CH acidity of the different N-arylated pyrroles 1 and indoles 2, obtained both for THF solution (Figure 5) and gas phase (see Supporting Information File 1), are presented in the current paper. A potential acidity of the methoxy groups in

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• of the ligand L. This corresponds to a decrease in the Lewis acidity of the cobalt center. Consequently, the picture evolves to the reaction of an electrophilic CO2 molecule with a nucleophilic alkoxide chain connected to a cobalt(III) center. The CO2 molecule reacts via the carbon atom with the

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• unsatisfactory, even when prolonging the reaction time to 36 h or raising the temperature to 100 °C. By carefully investigating the two routes in Scheme 3, we assumed that an appropriate base is in favor of the [1,5]H σ migration in route 2, as well as lowering the acidity of Eu(fod)3 to prevent 12b from

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• −0.95 V vs SCE. The results indicate: an increased acidity favours the formation of oxime 5 (Table 1, Nr. 1), whilst without a proton donor the olefin presumably is polymerized to a large extent (Table 1, Nr. 2). The addition of acetic acid in portions appears to be a good choice as a too high proton

Thiazole formation through a modified Gewald reaction

• Carl J. Mallia,
• Lukas Englert,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 875–883, doi:10.3762/bjoc.11.98

• (Figure 2) thus helping to identify certain attributes of the mechanism. For example, 2-phenylacetonitrile (44) failed to react most likely due to the lower acidity of the α-methylene protons. Diethyl 2-cyanomalonate (45), also proved unreactive, this substrate would be expected to form an extensively

Photocatalytic nucleophilic addition of alcohols to styrenes in Markovnikov and anti-Markovnikov orientation

• Martin Weiser,
• Sergej Hermann,
• Alexander Penner and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2015, 11, 568–575, doi:10.3762/bjoc.11.62

• significantly slower, since longer irradiations were needed. Only the addition of phenol failed completely. Since isopropanol and tert-butanol as sterically demanding nucleophiles gave the corresponding addition products in good yields, it was assumed that the acidity of benzyl alcohol, and more significantly

Fluoride-driven ‘turn on’ ESPT in the binding with a novel benzimidazole-based sensor

• Kai Liu,
• Xiaojun Zhao,
• Qingxiang Liu,
• Jianzhong Huo,
• Bolin Zhu and
• Shihua Diao

Beilstein J. Org. Chem. 2015, 11, 563–567, doi:10.3762/bjoc.11.61

• atom is transferred to an electronegative atom at the excited state [2][17][18]. By regulating the proton acidity of the H-bond donor which plays a vital role in the ESPT process, the biologically and chemically important anion would be distinguished by the different optical outputs for the interaction

• indicated the occurrence of hydrogen-bonding interaction between BIP and F−. Moreover, the acidity of the OH group of BIP was expected to be enhanced by anion binding, and the ESPT channel would be open [8][9][10][15]. The subsequent spectral behavior proved our assumption. The new peak at 376 nm occurred

• was 8.79 × 105 M−1, which was bigger than that obtained from UV–vis spectroscopy. This suggested the enhancement of the phenolic OH acidity by the photoexcitation [2][11][12][13][14][15]. Moreover, fluoride-dependent fluorescent intensity at 376 nm displayed an excellent linearity (R = 0.9880) in the

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• -acetylhydroxyamino acids. They were in fact the first researchers to at all investigate compounds belonging to this class of amino acid derivatives. Under the mantra «acidity favors O-acylation, while alkalinity favors N-acylation», they accomplished this feat by treatment of hydroxy-L-proline, DL-serine, DL

• products is too voluminous to justify any exhaustive listing in this work, thus for the purposes herein, it will suffice to point out that the outcome of acetylation reactions on such amino alcohols varied greatly depending on the acidity or alkalinity of the reaction medium. In a previous section, we were

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts

• Bin Yin,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2015, 11, 85–91, doi:10.3762/bjoc.11.12

• aromatic dithioacetal is more acidic compared to that of an aliphatic dithioacetal, the deprotonation of the former is faster than it is for the latter. Therefore, it can be stated that the product selectivity is controlled by the kinetic acidity of the cationic intermediate A [26][27]. With these facts in

• substrates. It is known that the acidity of the α-proton of N,N-diethylacetoamide is 4 to 5 times lower than that of acetone and ethyl acetate [35]. Therefore, the acidity of the α-proton of 1f having an amide group would be much lower compared to that of 1b and 1d having an ester and acetyl group

• fluorination of 1b and 1d (Figure 1a and Table 3, entries 2 and 4). Thus, it was found that due to the low acidity of the α-proton of 1f, fluorodesulfurization took place prior to α-fluorination even in the presence of Et3N·3HF containing the free base Et3N. In sharp contrast to these cases, α,α-bis(phenylthio

Anion effect controlling the selectivity in the zinc-catalysed copolymerisation of CO₂ and cyclohexene oxide

• Sait Elmas,
• Muhammad Afzal Subhani,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 42–49, doi:10.3762/bjoc.11.7

• amounts of CO2. Non-coordinating anions lead to a more electrophilic zinc centre with a stronger Lewis acidity, thereby triggering the homopolymerization in case of the CF3SO3− anion. In this context, it is known that the rate of the CO2 insertion into metal–oxygen bonds depends critically on the

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• ∙H2O, Cu(OAc)2∙H2O and Cu(NO3)2∙3H2O instead of CuSO4∙5H2O (Table 1, entries 2–4b). Among the Cu2+ salts tested, Cu(OAc)2∙H2O was found to be better than others and yielded 10% of 4a (Table 1, entries 3–4b). In the literature, we found that additives, such as Brønsted acids, enhance the acidity of the

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• presence of an equimolar amount of phenol (as a source of phenolic acidity) led to the formation of dihydroisoxazolopyridines 5a,c rather than benzoxazocines 6a,c thus supporting the assumptions. A plausible mechanistic rationale is outlined in Scheme 4. It should be firstly noted that the formation of any

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• , bromopropargyloxy ester 12 was converted using [Ni(tmc)]Br2 (tmc = 1,4,8,11-tetramethylcyclam) as catalyst, leading to cyclization products 13 and 14 (Scheme 5). When 12 was electrolyzed in absence of mediator, significantly lower yields were obtained [42]. The acidity of the reaction medium strongly influences the

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• energy is the less reactive and fails to participate in the photo-Favorskii rearrangement. Wan’s work clearly demonstrates, however, that the excited state acidity of 1-naphthols is much greater than 2-naphthols and that excited-state intramolecular proton transfer (ESIPT) for 1-naphthols occurs at both

• ][45][46][48]. In non-hydroxylic solvents, the (n,π*)3 dominates which leads to the classical α- and β-homolytic cleavage and H-abstraction reactions. For 2,6-HNA and 5,8-BQA, the reduction product, a methyl ketone, probably results from homolysis. The lower excited state acidity and the poor

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• by the formation of 4-nitrobenzaldehyde. This can potentially occur by benzylic deprotonation, due to the enhanced acidity of these protons in 1o or a reactive intermediate. Such a problem was not encountered in the reactions of other benzylic alcohols. Use of K2CO3 in place of DBU did not ameliorate

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• into 22 long reaction times were required and the high acidity led to the formation of side products. Nevertheless, the target compound 22 was isolated in a moderate yield of 59%. As a milder alternative, samarium diiodide was examined for the N–O bond cleavage [40][41][42][43][44][45]. With this

A promising cellulose-based polyzwitterion with pH-sensitive charges

• Thomas Elschner and
• Thomas Heinze

Beilstein J. Org. Chem. 2014, 10, 1549–1556, doi:10.3762/bjoc.10.159

• ). Moreover, the question arises how the pKa value is influenced by further substituents. Therefore, the acidity of the ammonium groups of ω-aminoethylcellulose carbamate [23], (3-ethoxy-3-oxopropyl)(2-aminoethyl)cellulose carbamate 6 and the polyzwitterion 7a were compared. Polycation 6 was titrated forth

A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges

• Martin Popr,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2014, 10, 1390–1396, doi:10.3762/bjoc.10.142

• of derivatizing agent along with an excess of base lead to the 6I-O-substituted products, while the preparation of 2I-O-substituted derivatives [15] takes advantage of the highest acidity of 2-OH hydroxy groups. A widely used methodology that leads to a variety of 6I-O-substituted analogues is the

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• formanilide (R = H) or chloroacetanilide (R = CH2Cl) as a substrate (Scheme 10) produced the expected phosphoramidate by a mechanism which simultaneously involved deacetylation. The higher reactivity of formanilide and chloroacetanilide, when compared to aniline, was explained by the higher acidity of the

• must be activated as a sulfonamide (or acetamide) to produce the expected phosphoramidate [42]. The authors, who used a phase-transfer agent, postulated that this activation resulted from the increase of the acidity of the N–H bond despite the evident reduction of the nucleophilic character (Scheme 14

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• cheaply available, making them seemingly ideal building blocks for the synthesis of such complex pyrone-containing molecules. As heterocyclic aromatic enols, they have a high acidity and dense functionality which leads to a diverse reactivity profile. This means that 4-hydroxy-2-pyrones are also useful

• high acidity of hydroxypyrones such as 3 (Scheme 1; R1 = H, pKa = 4.94 [13]), they would appear to be ideal coupling partners in the Mitsunobu reaction. We recently published an example of the Mitsunobu reaction using the compound 4-hydroxy-6-methyl-2-pyrone (3a) [14]. To the best of our ability, we