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

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• presence of Schreiner′s thiourea in the reaction medium enhances the acidity of the ammonium salt due to doubling their dual hydrogen bonding ability with the carboxylate and the alkoxy group of the ammonium salt. A thiourea derivative also enhances the nucleophilicity of the glycosyl acceptor by imparting

• -CO2Me of 3a (Figure 3d). Also, the magnification of the nucleophilicity of the glycosyl acceptor by the thiourea derivative results in shifting of the -OH peak from δ 2.70 to δ 3.62 (Figure 3d). Once this understanding was gained from 1H NMR studies, aryl thiourea cocatalyst 4 (10 mol %) was added with

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• β-aminoalcohols. The different nucleophilicity of the NH2 and OH groups determines the sequence of the reaction steps. In the reported cases, the initially formed N-(β-hydroxyalkyl)enamines 79 undergo spontaneous lactonization with the geminal alkoxycarbonyl group leading to the six-membered

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• -membered ring of intermediate 11 (Scheme 3). Although the reasons for such divergence in the reactivity are not completely understood, one could argue that the lower nucleophilicity of enolates derived from 8 as compared to that of enamine 1a could be responsible for this effect. Indeed in this case, the

• formation of the indoline ring was unambiguously confirmed by the crystal structure of compound 21ab (CCDC 1546063, Figure 2). It seems that the nucleophilicity of the hydrazine moiety prevailed, and the formation of the thermodynamically more favorable amide bond governed the overall direction of this

• transformation. It should be also taken into account that, unlike the aforementioned hydrazone structures 15 and 16, ketazinones appear to be more stable in keto-enamine form 17. We reasoned that the nucleophilicity of the ketazinone moiety can be substantially reduced via incorporation of excessive steric bulk

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• glycosyl hemiacetal 33 with one of its hydroxy groups free available as the acceptor producing disaccharide 34. The regioselectivity is presumably due to the higher nucleophilicity of the alkyl hydroxy group than that of the hemiacetal hydroxy group. This process can be repeated for chain elongation

• utilized to glycosylate iduronic acid 55, disaccharide 56 was obtained only in 31% yield along with aglycon transfer products, 57 (19%) and 58 (24%). The modest yield of the desired glycoside product resulted from the lower nucleophilicity of 4-OH as compared to the thioethyl moiety, which could compete

• nucleophilicity of the thiophenyl moiety due to the steric as well as electronegative effects of the phenyl group. The hemiacetal donor 49 glycosylated the thiophenyl glucuronate acceptor 50 in an excellent 91% yield using the preactivation protocol (Scheme 11c). The successful preparation of disaccharides 61 and

High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units

• Marco Leonardi,
• Mercedes Villacampa and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2017, 13, 1957–1962, doi:10.3762/bjoc.13.190

• ), piperazine (1i,j) or tetramethyldisiloxane (1k–o) fragments, was also feasible. Interestingly, the use of N1-(2-aminoethyl)ethane-1,2-diamine as the starting material was also possible, without interference from the secondary amino group in spite of its nucleophilicity, to give compound 1h. This kind of

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

• the hydrazine is slow, meaning that the nucleophilicity is greatly retarded compared to lower acid loadings. Nonetheless, considering that the subsequent fluorination step should proceed optimally under basic conditions [17], the lowest amount of acid which also provided a good yield was thus chosen

Influence of the milling parameters on the nucleophilic substitution reaction of activated β-cyclodextrins

• László Jicsinszky,
• Kata Tuza,
• Giancarlo Cravotto,
• Andrea Porcheddu,
• Francesco Delogu and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 1893–1899, doi:10.3762/bjoc.13.184

• , ZrO2 gave the best performances in reactions involving TU (Supporting Information File 1, Table S1, entries 16 and 17). Thus, NaN3 seemingly displayed stronger nucleophilicity than TU when stainless steel milling tools were utilized and vice versa for ZrO2 milling tools. In another set of experiments

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• sugar during GT-catalysed reactions, GTs are also classified as inverting or retaining (Figure 1). Inverting GTs operate via a SN2 mechanism in a single displacement step where an acid/base residue enhances the nucleophilicity of the acceptor, via an oxocarbenium-like transition state. Unlike inverting

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• -withdrawing group in the amine (lower nucleophilicity) and an electron-donating group in the isothiocyanate component (lower electrophilicity) led to prolonged grinding times necessary to achieve quantitative conversion. The reaction time in these cases was successfully reduced by LAG, providing N,N

• under ball-milling conditions by using two equivalents of sodium hydroxide. Deprotonation of the N–H group increased the nucleophilicity of the nitrogen atoms, enabling the nucleophilic displacement reaction with two equivalents of 4-bromobenzyl bromide to yield di(4-bromobenzyl)urea 34 in 41%, after a

• total of 34 hours of milling (Scheme 13b). This transformation showed that ball milling could potentially be applied to increase the nucleophilicity of an otherwise poorly reactive compound. In the course of our studies on mechanochemical desymmetrization, we also investigated the reaction of o-pda and