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

• to 83% in the equimolar reaction of 9 with 3. In addition, the product 10 was recovered unchanged after treatment with 6a irrespective of DIPEA. The nucleophilicity of 10 may be canceled by the two benzoyl groups. The product 10 was fairly stable to air and moisture, and thus E-structure was

• -triketones reacted with NHCs to afford bisacylated Breslow intermediates in high yield. However, their nucleophilicity was so weak that they were recovered unchanged in the reaction with enones. It was also found that the monoacylated Breslow intermediates changed reversibly to the resting state of acid

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• different nucleophilicity of both amino groups, the predictable formation of a hydrogen bond between the aromatic amino group (hydrogen bond donor) and the aliphatic NHR (hydrogen bond acceptor) could increase the nucleophilicity of the former and decrease the reactivity of the latter, favoring the chance

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• consumption of 11a–c (Table 1, entries 1–3, column 6) was good (75–100%), but insufficient for 11d–f (22–50%, Table 1, entries 4–6, column 6). Our explanation for the low conversions is a diminished amine nucleophilicity in the EWG-substituted dianilines 11d–f and reduced electrophilicity of the 12a due to a

• cycloadditions performed by p-TsOH (Table 1, column 4). From the above experimental results, we have proved that the regioselectivity of the cyclocondensation depends on both (a) the different nucleophilicity of the two amines from o-phenylenediamines 11a–f and (b) the electrophilicity of the α-carbonyl in 12a

• shifted H-N(1) and H-C(8), whereby coupling of HC(5 and 8) depends on type of the regioisomer). It was proved that observed regioselectivity of performed cyclocondensations depends on both a/ the different nucleophilicity of amine groups in diamine 11 (with two clusters of substituents: EDGs + halogens

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

• reaction. Removal of the OH groups at positions C2 of Glc, C1′and C3′-Fru resulted in no conversion at all. The authors demonstrated that not only these deoxygenations change the hydrogen-bonding network but also have a very large effect on the overall nucleophilicity of the disaccharide and its

Substitution of fluorine in M[C₆F₅BF₃] with organolithium compounds: distinctions between O- and N-nucleophiles

• Anton Yu. Shabalin,
• Nicolay Yu. Adonin and
• Vadim V. Bardin

Beilstein J. Org. Chem. 2017, 13, 703–713, doi:10.3762/bjoc.13.69

• PhC≡CLi is a consequence of the low nucleophilicity of PhC≡CLi. For instance, C6F6 and C6F5C6F5 do not react with PhC≡CLi in ether, although the addition of a coordinating solvent (DME, diglyme [39], THF [40]) accelerates nucleophilic substitution. C6F5CH3 bearing the non-electron-withdrawing

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• chemical properties, such as acidity and nucleophilicity, and thus to some extent, the synthetic methods could be developed analogously to each other. In this context, it is valuable to compare their existing synthetic methods for better understanding, so as to inspire organic chemists to invent new

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• nucleophilic attack of the phenolic hydroxy group; instead it reacted with water during the work-up process. This different outcome of this reaction compared to Borhan’s results might be attributed to the lower nucleophilicity of phenols compared to alcohols. Previously, Panda and co-worker converted

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• expected to produce high selectivity for the corresponding imidazolidinone 16 via the incorporation of CO2. The competing oxazolidinone formation should be limited as the nucleophilicity of nitrogen is more than that of the oxygen. Furthermore, the formation of dimers were expected to be supressed as 16

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• be a reason for the decrease in the N1 nucleophilicity. Nevertheless, the HOMO coefficient values found for the substituted 1,2-phenylenediamine were lower than those found for 1,2-phenylenediamine (8d) without a substituent. Similarly, for 8b smaller HOMO coefficients are obtained than for the

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• the repeating unit hexasaccharide 1 was envisioned. The union of trisaccharides 2 and 3 (Scheme 1, route A) was identified as the key step. The outcome of this late-stage block coupling was deemed risky considering the poor nucleophilicity of the C4 hydroxy group of the β-mannosazide in 3 combined

• ether protecting group 38 was recovered. The undesired outcome of this coupling step likely resulted from the poor nucleophilicity of 3 rather than a lack of reactivity of trisaccharide glycosylating agent 2, as demonstrated by an experiment in which model monosaccharide 37 [29] also failed to react

• protected mannosazide 4 was successfully glycosylated using building blocks 5 or 37 to yield the corresponding disaccharide in 21% and 37% yield, respectively. The failure of the [3 + 3] coupling to produce hexasaccharide 36 was apparently a result of the poor nucleophilicity of the C4 hydroxy group in 3

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• findings are surprising, as all three reactive groups are known to bind to cysteines which indicate a fine-tuned nucleophilic reactivity of the active site cysteine Cys112. The fine-tuned nucleophilicity towards our probes is supported by calculations of a mechanistic model where Cys112 is activated by

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• possible to overcome the barrier of 9 kcal/mol required to activate the substrate. At the same time, the corresponding sp2 structures 8b and 8c are characterized by the highest partial charges of the N-1 atoms (−0.202/−0.214 e) reflecting the nucleophilicity of these atoms that attack the electrophilic C-1

• satisfactorily. On the contrary, UP is not able to catalyze the nucleophilic attack of the structure 8c of 2SaThy owing probably to the lower nucleophilicity of the N-1 nitrogen atom (−0.109 e) compared to 2SUra for which the partial charge of −0.146 e of the N-1 atom was calculated (Table 1). With respect to E

Thiazol-4-one derivatives from the reaction of monosubstituted thioureas with maleimides: structures and factors determining the selectivity and tautomeric equilibrium in solution

• Alena S. Pankova,
• Pavel R. Golubev,
• Alexander F. Khlebnikov,
• Alexander Yu. Ivanov and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2016, 12, 2563–2569, doi:10.3762/bjoc.12.251

• sets of insufficiently resolved signals of other protons. The presence of two forms follows from the 13C NMR spectra as well. Taking into account the differences in nucleophilicity between the unsubstituted and phenyl-substituted nitrogen atoms of thiourea 1a, the phenyl group in compounds 3a,b is more

• had no effect on the regioselectivity of the addition to maleimide 2 forming thiazolidines 3h–k (Table 1). Although alkyl groups generally increase the nucleophilicity of the adjacent nitrogen atom as compared to the unsubstituted one, the methyl-substituted thiazoldine 3k having the methyl group

• (ratio 4k:3k after 2 h was 1:0.9, after 4 h it changed to 1:2.4). Whereas the formation of the isomer 4k corresponds to the relative nucleophilicity of the nitrogen atoms of thiourea 1f, the isomer 3k seems to be more thermodynamically stable. The choice of the solvent turned out to be crucial for the

Methylenelactide: vinyl polymerization and spatial reactivity effects

• Judita Britner and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 2378–2389, doi:10.3762/bjoc.12.232

• attack of the thiol takes place. This can be clearly seen in the 1H NMR spectra (Figures S18 and S19, Supporting Information File 1). Thioacetic acid was used as a potential chain-transfer agent due to its lower nucleophilicity. However, a complete thiol-Michael addition can be seen in Figure 8 (not full

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• per-6-halogenated CDs. The preparation is also carried out in a polar aprotic solvent, as in case of the azide exchange, while byproducts may also be similar despite the higher nucleophilicity of sulfur. The reaction under classic conditions usually requires large TU excess. Various per-6-alkylthio-β

Isosorbide and dimethyl carbonate: a green match

• Fabio Aricò and
• Pietro Tundo

Beilstein J. Org. Chem. 2016, 12, 2256–2266, doi:10.3762/bjoc.12.218

• with the presence of four oxygen atoms all in β position to each other that enhance the nucleophilicity of the hydroxy groups. Conclusion Among the top chemical opportunities from biorefinery carbohydrates D-sorbitol is a platform chemical of considerable interest that has led to intensive research in

• base. This result was ascribed to the neighbouring effect of the oxygen situated all in β-position to each other that most probably enhances the nucleophilicity of the corresponding hydroxy group. Furthermore the amphoteric catalyst hydrotalcite was extremely efficient in the synthesis of DMI when

Superelectrophilic activation of 5-hydroxymethylfurfural and 2,5-diformylfuran: organic synthesis based on biomass-derived products

• Dmitry S. Ryabukhin,
• Dmitry N. Zakusilo,
• Mikhail O. Kompanets,
• Anton A.Tarakanov,
• Irina A. Boyarskaya,
• Tatiana O. Artamonova,
• Mikhail A. Khohodorkovskiy,
• Iosyp O. Opeida and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 2125–2135, doi:10.3762/bjoc.12.202

• temperature for 1–24 h gives rise to 5-arylmethylfurfurals (yields of 17–91%) and 2-arylmethyl-5-(diarylmethyl)furans (yields of 10–37%). The formation of these two types of reaction products depends on the nucleophilicity of the arene. The same reactions under the action of acidic zeolites H-USY in high

• compounds were formed by hydroxyalkylation due to the interaction of species A with arenes (see related reactions [34][35][36][37][38]). The polymethylated arenes possess a sufficient π-nucleophilicity for the reaction with the protonated aldehyde group of the intermediates generated from 1a in TfOH

• (Table 4, entries 20–23). Under the superacidic conditions the substrates anisole and veratrole may be protonated at the oxygen atoms [33], thus leading to a decreased π-nucleophilicity of these arenes. It should be noted that in the case of zeolites we explored CS2 as low coordinating solvent to avoid

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• nucleophiles towards halo derivatives of main group elements where the DBU and DBN bicyclic rings remained unaffected [10][11]. Later in 1994, Lammers et al. observed the nucleophilicity of amidine bases with 4-halo-3,5-dimethyl-1-nitro-1H-pyrazole and their subsequent ring opening leading to the lactam

• carbohydrate–protein interactions [25], ligation and surfactant properties [26][27]. Although p-nitrophenyl carbonates were extensively utilized in these reactions, the nucleophilicity of amidine bases towards these carbonates was not encountered so far. In continuation of our interest in carbohydrates [28][29

• with DBU under the same conditions as described above, giving 6b and 7b in 82% and 87% yield, and 8b as a mixture of α and β anomers in 48% yield. Encouraged by these results, we turned to evaluate the nucleophilicity of DBN towards p-nitrophenyl carbonate derivatives (Scheme 2). Next, the reaction of

Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

• Jimena E. Díaz,
• María C. Mollo and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2016, 12, 2026–2031, doi:10.3762/bjoc.12.190

• considerably lower nucleophilicity of the arylamino group, procedures for N-alkyl or N-unsubstituted 2-iminoazacycloalkanes are usually not suitable for the synthesis of N-aryl derivatives. Ethyl polyphosphate (PPE) and trimethylsilyl polyphosphate (PPSE) are mild irreversible dehydrating agents of the Lewis

Synthesis of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones: Rearrangement of pyrrolo[1,2-d][1,3,4]oxadiazines and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles

• Kkonnip Son and
• Seong Jun Park

Beilstein J. Org. Chem. 2016, 12, 1780–1787, doi:10.3762/bjoc.12.168

• to 12a, the mechanism of the nucleophile-induced cyclization is proposed after considering Hart’s research on the synthesis of fumiquinazolines [22]. It was shown that the nucleophilicity of the N-acylnitrenium ion was increased when the oxygen ion was stabilized by counter ions such as lithium and

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

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• of 26% (28, Scheme 2). It is not yet clear as to why such a low conversion and isolated yield was obtained although the reduced nucleophilicity and higher potential for coordination of the triazole to the copper catalyst might inhibit catalyst turnover and account for this. Alternatively, using 3

• reactor blocking. Other substrates proved unreactive. In the case of starting materials 41–43 the reduced nucleophilicity of these substrates might account for the lack of conversion. By comparison, all three substrates (41–43) also failed to react under batch conditions using 2 equiv of Cu(OAc)2, 2 equiv

On the cause of low thermal stability of ethyl halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2016, 12, 1590–1597, doi:10.3762/bjoc.12.155

• nucleophilicity can be inferred from the NBO charges. Based only on NBO charges, halodiazoacetates may be expected to be even less nucleophilic than diethyl diazomalonate (see Supporting Information File 2 for the numbers). All of the investigated diazo compounds thermally extrude N2 to initially form a singlet

• temperature for 30 min. The solvent was removed and the crude product was purified by silica gel chromatography (5% EtOAc/hexane) to give 123 mg (0.457 mmol, 67%) of ethyl 1-bromo-2-phenylcyclopropanecarboxylate as a colorless oil. Relative stability and nucleophilicity of non-stabilized (R = H, alkyl) diazo

• halodiazoacetates (red color). Relative nucleophilicity of halodiazoacetates (red color). Synthesis of ethyl halodiazoacetates [11]. Proposed rate determining step for the thermal decomposition of 2a–c. Reaction conditions and half-lives (t1/2) of 2a–c. Cyclopropanation of styrenes with 2a–c. Supporting

On the mechanism of imine elimination from Fischer tungsten carbene complexes

• Philipp Veit,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2016, 12, 1322–1333, doi:10.3762/bjoc.12.125

• diferrocenyl derivative Cr(CO)5(E-2) from bulky Fc-NH2 [40][41] requires the presence of a base to increase the nucleophilicity of Fc-NH2 by deprotonation. In the presence of base, Cr(CO)5(E-2) decomposes readily in solution at room temperature releasing E-1,2-diferrocenylimine [43] E-3 (Scheme 1a) [27]. 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

• cyclic N-benzyloxycarbonyl acrylamides 75 and 77 in moderate to good yields and high enantioselectivity (Scheme 18a,b). Due to their attenuated nucleophilicity, electron-deficient amines were unreactive under the standard reaction conditions. Addition of 0.5 equivalents of free amine was found to be