Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• alkylation to 12c (Scheme 11). The mechanism of the reaction is based on the formation of an electron-rich ruthenium–phosphido complex that enhances the nucleophilicity at the phosphorus atom. This permitted the reaction to proceed with the less electrophilic benzylic chlorides 35 instead of bromides. The

• isolated as their air-stable phosphine–borane complexes 12c, 37 [59][60]. The group of Glueck has reported a method for the asymmetric alkylation of racemic secondary phosphines 36b by means of a chiral platinum-based catalyst 39 (Scheme 12) [61]. The enhanced nucleophilicity at phosphorus of the platinum

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• zwitterionic intermediates 9a,c which further cyclize to bisadducts 3a,c. The barriers for addition of the azirine and aziridine nitrogen lone pair of 1a,c, and 8a,c to ketene 6a increase in passing from compounds 1a, 8a to compounds 1c, 8c, because of a decrease in the nucleophilicity of the latter due to the

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• as a colorless crystalline product and 6b (43% yield) as yellowish crystals. This product could not be thermally cyclized into the corresponding pyrazole derivative, presumably due to the reduced nucleophilicity of the hydrazine nitrogen bearing the electron-deficient vinyl substituent (Scheme 4

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• nucleophilicity of the isocyanide used also seems important. Thus, isocyano butane provided the γ-lactams in high yields (81–93%), whereas more acidic ethyl 2-isocyano acetate showed less efficient conversion (7–13%). The stereoselectivity of the process was also studied, however, even with two chiral inputs no

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• one hand, as an electron withdrawing group, it decreases the nucleophilicity of the amine, thus avoiding the formation of detrimental Michael-type adducts with the alkene. On the other hand, it increases the α-acidity of the imine intermediate, thus favoring the azomethine ylide formation. Moreover

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• significant amounts in the cyclisation of amino diol 9c. This is explained by steric shielding of the amino function (→ decreased nucleophilicity) through the bulky phenyl group in α-position (compared to the less demanding Me and Bn side chains R of substrates 9a and 9c). As the R-substituent is in the β

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• hydrogenolysis, probably due to the low solubility and conversion of the fairly polar starting materials or intermediates. After these problems we tried to diminish the nucleophilicity of the amino group by addition of acid since this protocol has proved to be advantageous in other reduction processes of amines

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• that their nucleophilicity plays a determining role in the reactivity, since tert-butyl, cyclohexyl and benzyl isocyanides (Table 1, entries 1–3, 5–12) show a relatively high conversion, whereas the aromatic isocyanide was less reactive (entry 4) and the weaker nucleophiles TOSMIC and methyl

Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• cyclization [22]. Native amino acids are not suitable for fast reaction with epoxides at low temperatures, presumably due to protonation of their amine groups that results in a reduction of their nucleophilicity [23]. However, by means of the described α-amino-ε-caprolactam (7), we expect to increase the

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• bonds in one pot [66]. Electrophilic fluorocyclisation involving the intrinsic nucleophilicity of nitrogen can be a powerful tool to synthesise stereoselectively fluorinated N-heterocycles. This concept was exemplified by Shibata and co-workers [67], who in 2001 reported an elegant and efficient method

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• breaking the lithium clusters. This increases the nucleophilicity of the alkyne and favours the kinetic anti-adduct 14. Through the use of chelating metals (ZnBr2 in Et2O [59]) Herold noticed a reversal in selectivity favouring the syn-adduct 15 (1:20 anti/syn). Garner used a slightly different method. He

• increase of nucleophilicity diminishes the metal cations capability or chances to coordinate to the carbonyl groups. This promotes the attack of the nucleophile from the least hindered re side. Chelation control can also be achieved by the proper choice of solvents. Even changing from THF to Et2O is often

• –Wadsworth–Emmons [98][99][100] reactions are most commonly used for the introduction of a double bond to Garner’s aldehyde 1. Two things need to be considered before performing the olefination reactions: 1) epimerization of the stereocenter in the aldehyde (i.e. basicity vs nucleophilicity of the

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• fluorine, its hydration and thus reduced nucleophilicity [21]. The importance of this developing research field is reflected by the various review articles which have been published dealing with transition metal mediated or catalyzed fluorination [22][23][24], difluoromethylation [24], and

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• solvent. No external base was needed when the alcohol was the nucleophile. However, if the sulfonamide was the nucleophile, an external base such as t-BuOK was required presumably to increase the nucleophilicity of the sulfonamide. The Rueping group trapped the iminium ions using phosphites 76 to produce

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• combination of an electron deficient radical with an electron withdrawing substitution on N leads to a mismatching of polar effects with respect to k. Effect of arene substitution The results obtained so far strongly suggest that a matching of the nucleophilicity of the arene and the electrophilicity of the

• differences in ΔG‡ are low and within the errors of the computational method. Radical additions leading to dihydrobenzofurans and indanes So far, all radicals investigated contained a substituted aniline and the importance of the nucleophilicity of the arene has become obvious for a number of examples. To

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• hemiester generated in situ from the substrate and phenylboronic acid. It is proposed that complexation of the tertiary nitrogen to boron and coordination of the carbonyl act in a push/pull fashion, simultaneously enhancing the nucleophilicity of the boronate oxygen as well as imposing a chiral environment

Mechanistic studies on the CAN-mediated intramolecular cyclization of δ-aryl-β-dicarbonyl compounds

• Brian M. Casey,
• Dhandapani V. Sadasivam and
• Robert A. Flowers II

Beilstein J. Org. Chem. 2013, 9, 1472–1479, doi:10.3762/bjoc.9.167

• -SOMO activation [18][19][20][21]. The preferential formation of these isomers will be discussed below. While the nucleophilicity of alkyl radicals is well-documented [22][23][24], the radicals generated from β-dicarbonyl compounds have been shown to display more electrophilic character [25][26][27]. As

Isolation and X-ray characterization of palladium–N complexes in the guanylation of aromatic amines. Mechanistic implications

• Abdessamad Grirrane,
• Hermenegildo Garcia and
• Eleuterio Álvarez

Beilstein J. Org. Chem. 2013, 9, 1455–1462, doi:10.3762/bjoc.9.165

• (II) (3a–c) to the N,N’-diisopropylcarbodiimide (2) (Scheme 4). In this process, coordination of nitrogen to palladium should strongly reduce the nucleophilicity of the corresponding nitrogen atom and, therefore, the attack at the carbodiimide would be significantly slowed down compared to free

Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst

• Cybille Rossy,
• Eric Fouquet and
• François-Xavier Felpin

Beilstein J. Org. Chem. 2013, 9, 1426–1431, doi:10.3762/bjoc.9.160

• complicated. Indeed, the poor nucleophilicity of amino pyridine 17 and 18 precluded any tosylation under standard conditions. After extensive experimentations we found that the activation of the amino group with a strong base such as NaH allowed the preparation of the expected compounds 19 and 20 in

An aniline dication-like transition state in the Bamberger rearrangement

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2013, 9, 1073–1082, doi:10.3762/bjoc.9.119

• p-aminophenol was investigated by DFT calculations for the first time. The nitrenium ion, C6H5–NH+, suggested and seemingly established as an intermediate was calculated to be absent owing to the high nucleophilicity of the water cluster around it. First, a reaction of the monoprotonated system, Ph

• ortho- and para-orientation. Conclusion In this work, the Bamberger rearrangement was studied by means of DFT calculations. In the Introduction, three questions (a), (b), and (c) were raised: The nitrenium ion 7 was calculated to be absent. It cannot intervene owing to the high nucleophilicity of the

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• TEA. Nevertheless, the radiochemical yields for the formation of the 4-nitroaniline-derived sulfonamide [18F]18 were below 10%, even in the presence of TEA and DMAP. This can be attributed to the poor nucleophilicity of the amino group of 4-nitroaniline which is by far lower than that of aniline and 4

• -fluoroaniline. The difference in the nucleophilicity of these three aromatic amines is reflected by the pKa values of their corresponding ammonium ions decreasing from 4.65 over 4.58 to 1.02 for 4-fluoroaniline, aniline, and 4-nitroaniline, respectively [36]. To achieve satisfactory conversion of the 18F

Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

• Magnus Liljenberg,
• Tore Brinck,
• Tobias Rein and
• Mats Svensson

Beilstein J. Org. Chem. 2013, 9, 791–799, doi:10.3762/bjoc.9.90

• charge with Hückel theory [10][11], and an approach based on the frontier molecular orbital method [12]. More recent attempts include calculation based on Fukui indices [13], local softness and hardness reactivity descriptors [14], dual descriptors for both electrophilicity and nucleophilicity [15], and

Ring-opening reaction of 2,5-dioctyldithieno[2,3-b:3',2'-d]thiophene in the presence of aryllithium reagents

• Hao Zhong,
• Jianwu Shi,
• Jianxun Kang,
• Shaomin Wang,
• Xinming Liu and
• Hua Wang

Beilstein J. Org. Chem. 2013, 9, 767–774, doi:10.3762/bjoc.9.87

• between the structures of aryl groups and the efficiency of ring-opening reactions are discussed. Keywords: aryllithium reagents; 2'-arylthio-3,3'-bithiophene-2-carbaldehyde; dithieno[2,3-b:3',2'-d]thiophene; nucleophilicity; ring-opening reaction; Introduction Due to the promising optical and

• rarely been employed for this kind of reaction. Furthermore, the relationship between the nucleophilicity of organolithium reagents and the efficiency of the ring opening of fused thiophenes has not been discussed. In this paper, we present the ring opening of 2,5-dioctyldithieno[2,3-b:3',2'-d]thiophene

• be completed at −78 °C. Similar to the case of 2e bearing the EDG group of triphenylamine, 2h also gave a good yield of 3h (76%, Table 1, entry 8). These results indicate that an increase of the electron donating character of the substituted aryl groups leads to a higher nucleophilicity of the

A facile, rapid, one-pot regio/stereoselective synthesis of 2-iminothiazolidin-4-ones under solvent/scavenger-free conditions

• Murugan Sathishkumar,
• Sangaraiah Nagarajan,
• Poovan Shanmugavelan,
• Murugan Dinesh and
• Alagusundaram Ponnuswamy

Beilstein J. Org. Chem. 2013, 9, 689–697, doi:10.3762/bjoc.9.78

• . Apparently, the reason for this can be attributed to the retardation of the nucleophilic attack of the amines on the isothiocyanate due to the steric effect (Figure 2) in the former, and decrease of the nucleophilicity of the amines by the electron-withdrawing group in the latter, thus not affording the

Reductions of aldehydes and ketones with a readily available N-heterocyclic carbene borane and acetic acid

• Vladimir Lamm,
• Xiangcheng Pan,
• Tsuyoshi Taniguchi and
• Dennis P. Curran

Beilstein J. Org. Chem. 2013, 9, 675–680, doi:10.3762/bjoc.9.76

• measurement of the nucleophilicity parameter, N [14]. By this measure, NHC-boranes are among the best neutral hydride donors known, more reactive than distant relatives such as silanes, stannanes, and dihydropyridines, and more reactive even than their amine-borane cousins [15][16][17][18][19]. Despite being

A new intermediate in the Prins reaction

• Shinichi Yamabe,
• Takeshi Fukuda and
• Shoko Yamazaki

Beilstein J. Org. Chem. 2013, 9, 476–485, doi:10.3762/bjoc.9.51

• -diol or to the carbocation X. While the intervention is suggested to depend on the concentration of water, in aqueous media the cation is unlikely owing to the high nucleophilicity of the large water cluster. Geometries of the precursor and the transition states (TSs) of the Prins reaction of propene