Generation of 1,2-oxathiolium ions from (arysulfonyl)- and (arylsulfinyl)allenes in Brønsted acids. NMR and DFT study of these cations and their reactions

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov,
• Olesya V. Khoroshilova and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2018, 14, 2897–2906, doi:10.3762/bjoc.14.268

• strongly depends on the nucleophilicity of the quenching medium. Under the conditions of low nucleophilic work-up with aqueous HCl (Table 3, entry 4), the deprotonation takes place leading to butadiene Z-3a. The predominant formation of the Z-isomer of 3a may reveal that cation Ba undergoes deprotonation

• and recyclization, rather than species C. Quenching of species Ba with water (high nucleophilicity) affords alcohol Z-4a. The formation of compound 4a in exclusively Z-configuration may indicate that cation Ba reacts with H2O in SN2 manner, keeping in mind that carbon C5 in Ba possesses a large

• been studied by NMR and DFT calculations. Depending on electrophilic activator, reaction conditions (temperature, time), and nucleophilicity of media for quenching of solutions of 1,2-oxathiolium ions, these species may undergo various transformations leading to the selective formation of one of the

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• nucleophilicity and accessibility of the axial 4-OH versus the equatorial 3-OH [40], we wondered, if this could be used to simplify the synthesis of the α-D-GalpN3-(1-3)-D-GalpN3 unit. When consulting the literature, surprisingly few reports were describing diol glycosylations targeting the galacto-configured

• superior nucleophilicity and accessibility of the 3-OH compared to the axial 4-OH. Initially, a small screening of the glycosylation conditions expected to affect the selectivity was performed. As the donor 15 stems from the acceptor 9, it was decided to use a slight excess (1.2 equiv) of the “less

• % yield. Conclusion In conclusion we have shown, how the difference in nucleophilicity along with steric effects can be utilized to employ an unprecedented regioselective glycosylation on a 3,4-diol, resulting in up to 67% isolated yield. Following general guidelines can be given: With bulky 6-O

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• and has an unpaired electron in the axial dz2 orbital. It acts as a high efficient “radical trap” and reacts with alkyl radicals to yield alkylcob(III)alamin (Figure 1b). Four-coordinated cob(I)alamin has a paired electron in the axial dz2 orbital, resulting in high nucleophilicity with a Pearson

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

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

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• ’-diacylation products were observed due to the low nucleophilicity of the secondary amino group, bearing a deactivating aromatic ring and all desired compounds were obtained with excellent yields (Table 2). Then, the microwave-assisted cyclization reaction leading to 3,4-dihydroquinazolines 1 was initially

Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles

• James T. Fletcher,
• Matthew D. Hanson,
• Joseph A. Christensen and
• Eric M. Villa

Beilstein J. Org. Chem. 2018, 14, 2098–2105, doi:10.3762/bjoc.14.184

• symmetrical pairings of aldehyde and imine reactants. Under both low and high-temperature conditions, the strongly electron-withdrawing nitro derivative was shown incapable of undergoing condensation. This can be attributed to the poor nucleophilicity of 4-nitroaniline. Condensation efficiency was observed to

• increasingly spontaneous for electron-rich amines partnered with electron-poor formyltriazoles [42]. Another expected outcome was that the condensation steps a, c and d would favor electron-rich amines relative to electron-poor amines, due to their superior nucleophilicity. All high-temperature reactions were

• substituent pairings studied, greatly simplified reaction outcomes were observed for those with nitro substituents. Those trials employing nitroaniline as a reactant showed a lack of imine formation due to its poor nucleophilicity (Table 2, entries 1 and 15). Those trials employing nitro-functionalized

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• to both the electronics of the arene and the nucleophilicity of the amine. Particularly electron-rich arenes such as N-methylindole are not tolerated, as is the case for relatively nucleophilic amines such as imidazoles, anilines or alkylamines. The reported substrates are particularly valuable to

Functionalization of graphene: does the organic chemistry matter?

• Artur Kasprzak,
• Agnieszka Zuchowska and
• Magdalena Poplawska

Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177

• desired amide bond (Figure 2, step c). On the other hand, reactions with alcohols proceed at slower rates, for the difference in the nucleophilicity of a primary alcohol and a water molecule is not as prominent as the difference found in amine coupling. Steglich esterification is a widely applied approach

• Figure 6, steps b and c, there is significant concurrence in the nucleophilic attacks of the desired hydroxy group-bearing compound (Figure 6, step b) and water (Figure 6, step c) because of the similar nucleophilicity of these molecules. In other words, water only attacks the activated ester because of

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• of nitriles, the strategy was also probed with aromatic nitriles 9 that were reacted with 8 under the same reaction conditions. The nucleophilicity of the N atom in aromatic nitriles should be lower than that of aliphatic ones owing to the conjugation of the triple bond with the benzene ring. To our

• that various electron-donating and electron-withdrawing groups on the benzene ring were compatible with the reaction conditions furnishing the desired products 10i–r in good yields. This indicated that the nucleophilicity of the nitrogen atom of nitrile 9 is strong enough to override the electronic

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• building block A (Figure 1) under harsh conditions. To obtain dendrimer 6, we expected to exploit the nucleophilicity of the phenoxide groups in the N,N’,N”-tris(4-hydroxyphenyl)melamine B (Figure 1) based on the previous example of P. Gamez and co-workers [41], which involved reaction with 2-chloro[4,6-di

Direct electrochemical generation of organic carbonates by dehydrogenative coupling

• Tile Gieshoff,
• Vinh Trieu,
• Jan Heijl and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2018, 14, 1578–1582, doi:10.3762/bjoc.14.135

• nucleophilicity of carbonates is limited and therefore, the choice of suitable arenes is crucial. Heterofunctionalizations like fluoro, chloro, and methoxy groups are generally accepted, but it depends on the substitution pattern. The sensitive interplay of inefficient oxidation at highly positive oxidation

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• synthesis. In these bond formations, organometallics play an essential role because they possess various reactivities depending on the central metal ions that they own. For example, carbon has strong nucleophilicity when bonded to metals with low electronegativity, as demonstrated in the reaction of

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• unreacted BnTMS or BnBF3K. The results in Table 1 show that silyl groups seem to be superior to boron groups for the reaction to afford a good yield. The solvent choices were made based on low nucleophilicity and polarity being high enough to dissolve the hypervalent iodine starting material. Surprisingly

Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• approach to N-aryl imides is to employ aniline starting materials (Scheme 1b, left), as was done in the synthesis of pentoxazone and related herbicides [2]. The alternative aromatic substitution approach with imide anions (Scheme 1b, right) is hampered by their low nucleophilicity [3]. Therefore

• ). The Mayr nucleophilicity constant of azide [15] is 20.5 and high yield (95%) is observed in a reaction with 1a under relatively mild temperature (65 °C) and short reaction time (2 hours, Table 2, entry 1). The Mayr nucleophilicity constant for phthalimide is five-orders of magnitude lower (15.5) [3

• ] and under similar conditions leads to trace product (Table 2, entry 2). In order to obtain a high yield of 2a, albeit lower than given in entry 1, a higher temperature (100 °C) and a longer reaction time (24 hours) are required (Table 2, entry 3). This suggests that the contribution of nucleophilicity

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

• enolonium species leads it to react faster with the less-hindered tosylate despite its poor electronic nucleophilicity. Thus, when the strategy of converting the least hindered enolate into the enolonium species 4 is used even highly hindered TMS enol ethers 5 may be used with formation of tertiary carbon

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• non-bridging oxygen concerted with the attack of 2´-OH, which increases the nucleophilicity of O2´ and stabilizes the phosphorane intermediate, and proton transfer from the non-bridging oxygen to the departing oxygen, which destabilizes the phosphorane and stabilizes the leaving group (Scheme 2

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• (kcov/khydr), when reacting with an RNA primer. It will not be trivial to find such a leaving group, as the nucleophilicity of alcohols is quite similar to that of water, so that it is difficult to utilize the chemoselectivity toward reaction partners with different softness, pKa, or other structural

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• nucleophilicity of the α-position (as a result of the strong electron donating nature of the dithio group) with enhanced reactivity of the TFBs in comparison to the corresponding ketenes. Therefore, dithi(ol)anyl TFBs have been identified as interesting starting material for a feasible synthesis of organic

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

• ) with high regioselectivity without any traces of other possible regioisomeric pyrazolo[1,5-a]pyrimidines 169. The regioselectivity of the reaction was attributed to the higher nucleophilicity of the exocyclic primary amino group over the endocyclic amino group. Synthesis of pyrazolo[1,5-a]pyrimidine

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• two arenes with different nucleophilicity, which were reacted with one sulfinamide. The respective product with the stronger nucleophile is formed exclusively. In reactions with two arenes having similar nucleophilicity a mixture of the respective products was obtained. Sulfonyl halides and

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols

• Xinyun Liu,
• Johnny H. Phan,
• Benjamin J. Haugeberg,
• Shrikant S. Londhe and
• Michael D. Clift

Beilstein J. Org. Chem. 2017, 13, 2895–2901, doi:10.3762/bjoc.13.282

• . Phenethylamine (6q) provided only a 17% yield of the corresponding imine (7q, Table 3, entry 7), potentially due to its increased nucleophilicity, which may result in inhibition of catalysis via condensation with quinone 2c. We also tested several electron deficient amides (6r−t) in these reactions (Table 3

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• -trifluoromethylated analogues in the presence of trimethylphosphine, with moderate to excellent yields (Scheme 33). The higher nucleophilicity of trimethylphosphine versus triphenylphosphine and the water solubility of trimethylphosphine oxide byproducts were essential elements in choosing the reducing agent. Both

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

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

• -aminobenzothiazole with acetophenones [55] or aldehydes and nitroalkanes [56]. Because the bicyclic structure of 2-aminobenzothiazole is more stable than aminopyridines and thioureas, the nucleophilicity of the aromatic N atom is reduced. A stronger base, KOt-Bu, is therefore needed for in situ bromination to form

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• photosensitivity and hence could be used in OLED devices [68]. Also these compounds display high nucleophilicity in reactions with electrophiles which are often accompanied by a variety of thiophene heterocycle transformations, and hence could be successfully used for their further functionalization [69

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• efficient and regioselective synthesis of pyrazolo[1,5-a]pyrimidines and aryl[heteroaryl]pyrazolo[1,5-a]pyrimidines in acetic acid under reflux. The regioselectivity was attributed to the high nucleophilicity of the amino group in 3-amino-5-methyl-1H-pyrazole and the high electrophilicity of the β-carbon

• 5h. The first nucleophilic attack from the amino group of 5-aminotetrazole was evidenced by HOMO coefficient calculations (Table S3 in Supporting Information File 1). The highest HOMO coefficient for the NH2 group indicates the superior nucleophilicity of the NH2 group in the aminotetrazole molecule