Direct catalytic arylation of heteroarenes with meso-bromophenyl-substituted porphyrins

• Alexei N. Kiselev,
• Olga K. Grigorova,
• Alexei D. Averin,
• Sergei A. Syrbu,
• Oskar I. Koifman and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2017, 13, 1524–1532, doi:10.3762/bjoc.13.152

• described in the arylation reactions. In this connection we considered it important to develop an alternative approach to heteroaryl-substituted porphyrins using catalytic arylation of easily accessible meso-(bromophenyl)porphyrins with heterocycles possessing “acidic” C–H bonds, such as benzoxazole (pKa

• 24.4), benzothiazole (pKa 27.3), and N-methylbenzimidazole (pKa 32.5) [30]. Starting mono- and di(p-bromophenyl)-substituted porphyrins 1 and 11 were synthesized according to a described procedure [31], their analogues 2, 10, 12 were obtained using essentially the same approach. Results and Discussion

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• aldehyde or ketone) making this center more electrophilic (Scheme 1) [3]. Secondly, the pKa value of the anomeric OH group (glucose pKa ≈ 12.5 [9] or 14 [10]) is several orders of magnitude lower than for the other hydroxy groups (pKa ≈ 16–18) [9][10] so a careful selection of the base should allow for the

• decasaccharide donors. Shoda and co-workers proposed the differential reactivity at the anomeric center (Scheme 24, glucose shown for convenience) can be explained by the lower pKa (≈12.5–14) of the C1–OH [9][10][77]. They believe that the base-promoted nucleophilic attack of the anomeric OH (either the α or β

Sugar-based micro/mesoporous hypercross-linked polymers with in situ embedded silver nanoparticles for catalytic reduction

• Qing Yin,
• Qi Chen,
• Li-Can Lu and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 1212–1221, doi:10.3762/bjoc.13.120

• absorption peak at 317 nm of observed for the neutral 4-NP solution, the absorption at 400 nm is attributed to the 4-nitrophenolate ion. The latter is generated through deprotonation of 4-NP (pKa = 7.15) upon the addition of NaBH4 [41]. As can be seen from Figure 5a, the absorption peak of the substrate

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• with hydroxylamine-O-sulfonic acid followed by the reaction with HBF4 according to a previously described method [30]. Salts 1b,c were prepared by direct N-amination of the corresponding pyridines with O-mesitylsulfonylhydroxylamine. In view of difficulties in obtaining experimental pKa values of

• different positions of pyridinium cations we carried out DFT calculations [31] at the M06-2X 6-31+G(d,p) [32] level of theory with SMD [33] solvation (Figure 1, see also Supporting Information File 1). As expected, in all cases the NH2 group is the most acidic. The NH2 group is usually ≈12–13 pKa units more

• acidic than α-C–H hydrogens. However, the difference in pKa of NH2 and CH3 groups of the 4-methyl-1-aminopyridinium cation is not so high and the NH2 group is only 2.7 units more acidic. 1-Aminopyridinium and 4-methyl-1-aminopyridinium cations have similar pKa values for NH2 and α-C–H groups. The 4

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• -carboxylic acid because of its relatively low pKa (compared with non-carboxylate substituted analogs) and the possibility of using an ester linkage as a tether. We found that the heretofore unknown dicyclohexylcarbodiimide (DCC) mediated coupling between para-quinols and 1,3-dithiane-2-carboxylic acid

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• in fact, epimerizing KRs bind their substrates in two distinct modes. In the first, which is only available to the substrate bearing the non-epimerized methyl center, the thioester and C-3-keto groups are aligned so that the pKa of the C-2 proton is suitably depressed, allowing facile catalysis by KR

(Z)-Selective Takai olefination of salicylaldehydes

• Stephen M. Geddis,
• Caroline E. Hagerman,
• Warren R. J. D. Galloway,
• Hannah F. Sore,
• Jonathan M. Goodman and
• David R. Spring

Beilstein J. Org. Chem. 2017, 13, 323–328, doi:10.3762/bjoc.13.35

• substituents initially seems counter-intuitive, as it might be predicted that these could attenuate the ortho-hydroxy’s ability to coordinate to the Cr centre. Although the effect appears to correlate with lowered pKa of this hydroxy group, moderate amounts of (Z)-product are generated when this group is

Spectral and DFT studies of anion bound organic receptors: Time dependent studies and logic gate applications

• Srikala Pangannaya,
• Neethu Padinchare Purayil,
• Shweta Dabhi,
• Venu Mankad,
• Prafulla K. Jha,
• Satyam Shinde and
• Darshak R. Trivedi

Beilstein J. Org. Chem. 2017, 13, 222–238, doi:10.3762/bjoc.13.25

• relative dependence of the anion concentration on the reacting species. Similarly, the rate constants have been calculated for R1 and R2 in the presence of fluoride. The lower order of magnitude of the rate constant in the presence of F− ions could be correlated to the pKa value of 3.2 (F− ion) in

• comparison with AcO− ion whose pKa value is 4.8. The time response of receptors R1 and R2 in the presence of AcO− ion is represented in Supporting Information File 1, Figures S17 and S18. The observed rate constants at different wavelengths for R1 and R2 are summarized in Table 2. 1H NMR titration studies To

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• red-shifted absorption bands and causes a dual emisson, i.e., a combination of emission bands of the hydroxyquinolizinium and its deprotonated form. Whereas this compound is a weak acid in the ground state (pKa = 7.9), it has a strongly increased acidity in the excited state (pKa* = 0.4). As a result

• , the blue-shifted fluorescence of the hydroxyquinolizinium becomes dominant only under strongly acidic conditions. In addition, it is shown that 3-hydroxynaphtho[1,2-b]quinolizinium binds to cucurbit[7]uril (CB[7]) with moderate affinity (Kb = 1.8 × 104 M−1, pH 5) and that the pKa and pKa* values of

• acidity or basicity. In fact, it was shown that the pKa of organic acids and bases often shifts by orders of magnitude upon association with CB[n] [16][17][18][19][20][21][22][23][24], which may be used, e.g., to modify catalytic activity [6] or for sensing purposes [7]. Notably, the same effect was

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• electronegativity of the R group is probably also important; when more electropositive (as Si), the oxygen atoms become more electron rich and their repulsion becomes larger. Changing the conformation of a heterocycle has, as mentioned, been studied using the piperidine model system. The pKa of the corresponding

• the reactivity of glycosyl donors with the pKa of the corresponding piperidinium ions. Conformational change induced by bulky vicinal protective groups such as TBS, TIPS and TBDPS. The vicinal clash overrules the 1,3-diaxial interaction, which is less influenced by bulky silyl ethers as these can

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• substantial dipole moment (≈4.5 D) almost aligned with the C5–H bond and the relatively high acidity of this position (pKa(DMSO) = 27–28, for the 1H-tautomer). These heterocycles, which are easily available from 1,3-cycloaddition of alkynes and azides, can both form strong C–H bonds with hydrogen bond

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• basicity of these purine nitrogen atoms, because N1 represents the major protonation site, followed by N7 and N3. This order is deduced from the macroscopic pKa values that were measured for adenine, 9-methyladenine, and adenosine [11]. Importantly, there is growing evidence that the pKa values of

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• calculated (total polar surface area; TPSA) and measured (pKa, log P/D and Pe) parameters are shown in Table 1. The lipophilicity of neutral species of naringenin and dracocephins A and B are 3.39, 2.52 and 2.39, respectively. Similarly to this lipophilicity trend, the TPSA value of (±)-naringenin is lower

• than dracocephins A and B, however, there is no difference between the calculated TPSA values of 2a–d and 3a–d. The pKa values of the three phenolic hydroxy groups of the evaluated compounds are quite similar and these are in the range of 6.5 and 12.0. Among these proton-dissociation constants, the

• lowest acidic pKa values are predominant in physiological environment, which is also indicated by the difference of log D values between pH 7.4 and pH 6.5. The blood–brain barrier (BBB) specific penetration of dracocephins isomers has also been studied by the PAMPA (parallel artificial membrane

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• recognition motif for PKA (cAMP-dependent protein kinase) that enables enzymatic phosphorylation. We have analyzed the pathway of amyloid formation and the influence of enzymatic phosphorylation on the different states along the conformational transition from random-coil to β-sheet-rich oligomers to

• binding [43]. Additionally, phosphorylation may be found to direct desired behaviors in the currently intensively studied area of amyloid-based biomaterials. In this report we show the use of the negatively charged phosphate group to control the aggregation process. Using PKA and ATP (adenosine

• Peptide model Peptide KFM6 follows a typical coiled-coil heptad repeat sequence and it includes five amino acids (-R-R-A-S-L-) in positions 20–24, in proximity to the C-terminus, that serve as the recognition motif for PKA. The crucial role of this recognition motif for efficient phosphorylation has long

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• optimized conditions (Table 1, entry 4), we examined the scope of the catalytic system, Et3B/ Pd(OAc)2/PPh3, for a wide range of 1,3-dicarbonyl compounds and related derivatives (pKa = 9–14) [29][31] using two typical MBH alcohols 1a and 1b. The results of this study are summarized in Table 2. Like diethyl

• malonate (2a), the malonate derivative 2b (pKa = 13) [29] similarly reacted with the allylic alcohol 1a in the presence of the catalytic system Pd(0)/Et3B to exclusively give the mono-allylated product 3a in 65% yield, whereas the same reaction with ethyl 3-cyano-3-oxopropanoate (2c, pKa = 10.7) [43] whose

Experimental and theoretical investigations into the stability of cyclic aminals

• Edgar Sawatzky,
• Antonios Drakopoulos,
• Martin Rölz,
• Christoph Sotriffer,
• Bernd Engels and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 2280–2292, doi:10.3762/bjoc.12.221

• of the conformational energy of the ring system and pKa values of the N-3 nitrogen atom. Conclusion: Cyclic aminals are stable compounds when not exposed to acidic media and their stability is mainly dependent on the conformational energy of the ring system. Therefore, for the preparation and work-up

• the test compounds, as protonation of the tetrahydroquinazoline system is expected to be an essential factor of hydrolysis induction. Theoretically, protonation might occur at the anilinic N-1, the aliphatic N-3 or by double protonation of N-1 and N-3. Therefore the pKa values of both nitrogens of the

• corresponding fragments. Therefore, compounds with a higher pKa value at the N-3 nitrogen might increase the hydrolysis sensitivity of these compounds due to their faster protonation, like for compound 9b. Computational studies as well as experimental data revealed that the formation of tetrahydroquinazolines

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• considered (Scheme 6). The quinolin-2-one 13 was predicted to be a more amenable alkylation partner than the THQ 14 due to the likely lower pKa of the amide proton. To assess this, 13 was reacted with NaH and 2-iodopropane in DMF at 80 °C overnight. However, 13 displayed a marked lack of reactivity towards

Dinuclear thiazolylidene copper complex as highly active catalyst for azid–alkyne cycloadditions

• Anne L. Schöffler,
• Ata Makarem,
• Frank Rominger and
• Bernd F. Straub

Beilstein J. Org. Chem. 2016, 12, 1566–1572, doi:10.3762/bjoc.12.151

• copper(I) acetate and sodium acetate as additional base in order to deprotonate the thiazolium salt 1b and to form the bisthiazolylidene copper(I) complex 2. Due to the relatively high acidity of the thiazolium precursor (pKa ≈ 18 [44]), a weak base such as sodium acetate yields small equilibrium

Flow carbonylation of sterically hindered ortho-substituted iodoarenes

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

Beilstein J. Org. Chem. 2016, 12, 1503–1511, doi:10.3762/bjoc.12.147

• , did not significantly change the isolated yield of 5. However, changing to the stronger base DBU (pKa in water at 25 °C = 13.5) [40] dramatically reduced the isolated yield (Table 1, entry 8). A wider temperature range was also investigated (Table 1, entries 9–11). This resulted in only a small

The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals

• Sonia L. Repetto,
• James F. Costello,
• Craig P. Butts,
• Joseph K. W. Lam and
• Norman M. Ratcliffe

Beilstein J. Org. Chem. 2016, 12, 1467–1475, doi:10.3762/bjoc.12.143

• is non-trivial [6][8][10][12][13]; and indeed the debate about the factors influencing the overall rate of reaction and the synchronicity of steps has yet to achieve consensus [11][14][15]. Factors such as solvent [13], catalyst pKa [9], –OR basicity [6][16][17], the kinetic anomeric effect [18], the

Reactivity studies of pincer bis-protic N-heterocyclic carbene complexes of platinum and palladium under basic conditions

• David C. Marelius,
• Curtis E. Moore,
• Arnold L. Rheingold and
• Douglas B. Grotjahn

Beilstein J. Org. Chem. 2016, 12, 1334–1339, doi:10.3762/bjoc.12.126

• ) have been shown to form an imidazolyl ligand (e.g., 2) after deprotonation with a basic proton-accepting nitrogen (Figure 1). We are unaware of reports on an experimentally determined pKa value of a PNHC imidazolidene complex, but looking at related derivatives, Isobe showed that a 2-palladated

• pyridine was 3.57 pKa units more basic than pyridine [9][10]. Considering reactions other than simple proton transfer, imidazol-2-yl complexes have recently been used to bind to a second transition metal [11]. Additionally, Cp*Ir complexes from our group [12] demonstrated heterolysis of the H–H bond of H2

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• for a few times without activity loss. However, a long reaction time (120 h) was needed to achieve good results, and the low yields for N-unprotected substrates could be explained by the fact that the amide NH (pKa in DMSO ≈18.5) is more prone to be activated by K2CO3 than MeCN (pKa = 25). The long

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• their pKa values (approximately 19 in DMSO) [19] are much higher, one exception being thioesters [20][21] and pyrazoleamides [22]. As an alternative, some specific heterocycles have been proposed as carboxylic acid surrogates. Examples of this type of heterocycles are oxazol-5-(4H)-ones (or azlactones

cis–trans-Amide isomerism of the 3,4-dehydroproline residue, the ‘unpuckered’ proline

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2016, 12, 589–593, doi:10.3762/bjoc.12.57

• isomerism; fluorine; pKa; proline; Introduction The sole genetically encoded secondary amino acid proline (Pro, 1) is known for its unique properties in biological systems. In particular, Pro residues are often found in the s-cis peptidyl-Pro conformation, due to the low energy difference between the s

• models. Data on Pro (1) and (4S)-trifluoromethylproline (3) is used for comparison. Results and Discussion Firstly, we determined the pKa of the ammonium group in the free amino acids (Table 1). Overall the values demonstrate a 0.9 pKa reduction upon introduction of the 3,4-double bond, and a 2.2 pKa

• , this, indeed, has an orientation close to the equatorial CF3-group placement in 3, and is not axial. Next, we determined the pKa of the carboxyl groups in N-acetyl amino acids for two rotameric forms separately (Table 1). All four compounds exhibited similar ΔpKa values [36][37]. Though, absolute

Interactions between 4-thiothymidine and water-soluble cyclodextrins: Evidence for supramolecular structures in aqueous solutions

• Vito Rizzi,
• Sergio Matera,
• Paola Semeraro,
• Paola Fini and
• Pinalysa Cosma

Beilstein J. Org. Chem. 2016, 12, 549–563, doi:10.3762/bjoc.12.54

• greater than 9, with a pKa of ca. 9 as described in [26]. Under the latter conditions, the S4TdR-main absorption band located at 337 nm in neutral medium shifted to 321 nm. Moreover, the high molar absorption coefficients (ε) evaluated in [26] suggested that the absorption band of S4TdR was probably