Development of variously functionalized nitrile oxides

• Haruyasu Asahara,
• Keita Arikiyo and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2015, 11, 1241–1245, doi:10.3762/bjoc.11.138

• , entries 1–4). In addition, the nucleophilic substitution also proceeded by employing neutral amines. The reaction of 8 with propylamine proceed smoothly, leading to N-propylamides 9c and 10c (Table 2, entries 5 and 6). The substitution reaction was influenced by the bulkiness of the amines. Heating at 120

• °C was required for the substitution reaction by sec-butylamine. However, in the case of tert-butylamine, even when the reaction was conducted in a sealed tube at 120 °C, only a small amount of amide was observed (Table 2, entries 7–10). On the other hand, a cyclic secondary amine, pyrrolidine

• amines underwent the substitution reaction, leading to 5c–f in good to moderate yields (Table 3, entries 3–6). It was noteworthy that, because of high reactivity of 12 caused by the isoxazole ring [20], the methylamino group could be replaced by a bulky tert-butylamino moiety. Conversion of the N

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• etc.) [86]. The synthetic strategy relied on reacting chlorodiphenylmethane (93) with an excess of dimethylaminoethanol (94) via a nucleophilic substitution reaction (Scheme 16). As both starting materials are liquid at ambient temperature the use of a solvent could be avoided allowing direct

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• computational analysis of the hydrolysis of the chlorophosphites BIFOP–Cl (1) and O–BIFOP–Cl (3, as well as the smaller model system 2-chloro-1,3,2-dioxaphospholane 8) provides further comparison of the >P–Cl reactivity. The nucleophilic substitution reaction takes place at a triple-coordinated chlorophosphite

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• and release cation pool method [42]. Schematic illustration of the anodic substitution reaction system using acoustic emulsification. Figure redrawn from reference [45]. Example of a chiral auxiliary Shono-oxidation intermediate [69]. Application of anodic oxidation to the generation of new carbon

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• used readily available N-(o-halobenzyl)arylamines as starting materials [17]. The o-haloarylbenzylamines (obtained by nucleophilic substitution of various anilines with 2-iodobenzyl chloride) gave the corresponding amide anions by an SRN1 substitution reaction in NH3 or DMSO as solvent under

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• ability of BtO− to function as a nucleofuge, led us to explore its displacement. In this context, several 1-alkoxy-1H-benzotriazoles obtained from benzylic alcohols underwent substitution reaction with a range of nucleophiles, and a simple alkyl derivative also underwent reaction although the reaction was

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular S_N2 reaction

• Yiwen Xiong,
• Ping Qian,
• Chenhui Cao,
• Haibo Mei,
• Jianlin Han,
• Guigen Li and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 1802–1807, doi:10.3762/bjoc.10.189

• anti-chloroamine intermediate A. The second step involves a typical intramolecular SN2 substitution reaction of intermediate A with the aid of benzylamine, to give the aziridine intermediate B. The intermediate B undergoes a SN2 nucleophilic process attacked by benzylamine, leading to the formation of

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• substitution reaction of chloride with NaN3 (Scheme 3) led to the corresponding azido derivative 15, which was used to “click” both the cone (8) and 1,3-alternate (18) pentynoic amides. Compound 18 was obtained from the corresponding 1,3-alternate p-aminocalix[4]arene 17 [47] by a reaction with EDC in CH2Cl2

Magnesium bis(monoperoxyphthalate) hexahydrate as mild and efficient oxidant for the synthesis of selenones

• Andrea Temperini,
• Massimo Curini,
• Ornelio Rosati and
• Lucio Minuti

Beilstein J. Org. Chem. 2014, 10, 1267–1271, doi:10.3762/bjoc.10.127

• , dihydrooxazine and pyrrolidines from acylamino phenyl selenides [14]. Interestingly, the intramolecular substitution reaction of a phenylselenonyl group was used on enantioenriched γ-hydroxyalkyl phenyl selenides to obtain optically active 2-substituted tetrahydrofurans [15] (see Scheme 2). In this article, we

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

• Zeng-Wei Lai,
• Rong-Fei Yang,
• Ke-Yin Ye,
• Hongbin Sun and
• Shu-Li You

Beilstein J. Org. Chem. 2014, 10, 1261–1266, doi:10.3762/bjoc.10.126

• ][4][5]. Despite extensive investigation and noteworthy advances in this field, several challenges remain to be solved. For instance, with monosubstituted allyl substrates, the palladium-catalyzed allylic substitution reaction prefers to give linear products rather than the branched ones [6][7][8][9

• ] (Scheme 1). Accordingly, the regio- and enantioselective allylic substitution reaction of monosubstituted allylic substrates to preferably obtain the branched products is one of the continuing challenges. To our knowledge, there are several cases in which high levels of both regio- and enantioselectivity

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• furnished the desired diastereomeric α-azidotetrahydrofuranones in a ratio comparable to that of the direct oxidative azidation of 8 (Scheme 6). Slightly higher selectivities in favor of the trans-configured α-azidofuranone could be observed when the substitution reaction was run for a shorter period. This

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• bicyclic ring system of the highly substituted aromatic 1.104 (Scheme 19). A SNAr reaction is then used to introduce the saturated piperidinopyrrolidine appendage 1.105 to furnish the desired structure [57][58][59][60]. In order to obtain a high yield for the substitution reaction a one-pot procedure was

Cyclization of substitued 2-(2-fluorophenylazo)azines to azino[1,2-c]benzo[d][1,2,4]triazinium derivatives

• Aleksandra Jankowiak,
• Emilia Obijalska and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2013, 9, 1873–1880, doi:10.3762/bjoc.9.219

• product (1.445 ± 0.005 Å). A detailed analysis of the DFT results for the azopyridine series demonstrates that the rate of cyclization only correlates with the character of the substituent at the benzene ring and does not depend on the pyridine ring. For a simple nucleophilic aromatic ipso-substitution

• reaction (NAS) electron-donating groups in the C(4) position of the pyridine ring in 4 should increase the reaction rate. Computational results demonstrate the contrary and as the electron donation of the substituent R increases in the order H (4a) < CH3 (4b) < OCH3 (4g) so does the activation energy

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• used for the activation of chloropyrimidines toward a nucleophilic substitution reaction with amines. The subsequent treatment of the obtained products with aq H2SO4 can lead to either N-denitrosation to obtain 4,6-pyrimidinediamines or to a Fischer–Hepp type rearrangement to obtain 5-nitroso-4,6

• recognized that a 6-chloro substituent is activated by the N-nitroso moiety in position 4 of the pyrimidine ring which facilitates nucleophilic substitutions. Moreover, after completion of the substitution reaction, N-nitroso moieties can be easily removed by short heating in diluted sulfuric acid [16]. When

• be explained by the stronger activation of the pyrimidine ring by the tertiary amine moiety (morpholine is a better activator than methyl, methylthio or acetamido groups). The prepared requisite N-nitrosated compounds 2 easily undergo the subsequent nucleophilic substitution reaction with amines. The

Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

• Qiang Wei,
• Ya-Yi Wang,
• Yu-Liu Du and
• Liu-Zhu Gong

Beilstein J. Org. Chem. 2013, 9, 1559–1564, doi:10.3762/bjoc.9.177

• . Finally, we demonstrate the synthetic application of this reaction in the construction of the 3a-(phenylselenyl)bispyrrolidino[2,3-b]indoline core structure (Scheme 2). Under the optimized reaction conditions, the enantioselective substitution reaction gave 4a in 78% yield and 86% ee. However, when the

Total synthesis of ochnaflavone

• Monica M. Ndoile and
• Fanie R. van Heerden

Beilstein J. Org. Chem. 2013, 9, 1346–1351, doi:10.3762/bjoc.9.152

• ][23][24]. We have opted to prepare the diaryl ether by using an aromatic nucleophilic substitution reaction. 4-Fluorobenzaldehyde (2) is a readily available starting material, and under basic conditions it reacted with isovanillin (3) to form the diaryl ether 4 in a high yield. The next step was the

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

• Qin Fu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 918–924, doi:10.3762/bjoc.9.105

• -alkyl groups and without N-substituent in the presence of potassium carbonate as a base catalyst. When two equivalents phenacyl bromides were used in the reaction, the N-substitution reaction of isatin also finished with the formation of spiro-oxirane-oxindoles. Keywords: Darzens reaction; isatin

Kinetics and mechanism of the anilinolysis of aryl phenyl isothiocyanophosphates in acetonitrile

• Hasi Rani Barai and
• Hai Whang Lee

Beilstein J. Org. Chem. 2013, 9, 615–620, doi:10.3762/bjoc.9.68

• substituent effects of X on the reaction rates are not compatible with a typical nucleophilic substitution reaction. The Hammett and Brönsted plots with X are biphasic concave upwards with a break region between X = H and 4-Cl (break point of σX ≈ 0.13), giving unusual positive ρX and negative βX values with

• X = 4-Cl and 3-Cl. Positive ρX (and negative βX) values indicate that the nucleophilic N atom becomes more negative in the TS compared to in the ground state (GS). The substituent effects of Y on the reaction rates are consistent with a typical nucleophilic substitution reaction, and the rate

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• thiolate anion by the addition of 2 equiv of KOt-Bu. Different chemical transformations are possible from the arene thiolate ions formed; for example, oxidation to the diaryl disulfide, subsequent nucleophilic substitution reaction with alkyl halides to afford alkyl aryl sulfides, or a second copper

Polymerization of novel methacrylated anthraquinone dyes

• Christian Dollendorf,
• Susanne Katharina Kreth,
• Soo Whan Choi and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 453–459, doi:10.3762/bjoc.9.48

• obtained (Scheme 1). Polymerizable green dye 2 based on anthraquinone The synthesis of the green anthraquinone based monomeric dye 2 is shown in Scheme 1, step a. 5,8-Dichloro-1,4-dihydroxyanthraquinone was first subjected to a nucleophilic substitution reaction with 2-(4-aminophenyl)ethanol to give a

Synthesis of a novel chemotype via sequential metal-catalyzed cycloisomerizations

• Bo Leng,
• Stephanie Chichetti,
• Shun Su,
• Aaron B. Beeler and
• John A. Porco Jr.

Beilstein J. Org. Chem. 2012, 8, 1338–1343, doi:10.3762/bjoc.8.153

• cyclopropane 6 (Figure 2, Supporting Information File 1). We next focused on an evaluation of the general scope of the reaction with regard to aryl and alkyne substitution. Reaction utilizing an electron-poor trifluoromethyl-substituted diynyl benzaldehyde 8 was successful, producing product 9 in moderate

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• chemical library synthesis. Thus, we chose to investigate the Pd-catalyzed benzylic substitution reaction of (coumarinyl)methyl acetates with various nucleophiles. In the forthcoming sections, the coupling of this coumarin template to arylboronic acids [56][57][58][59][60][61], amines [47] and

Highly selective synthesis of (E)-alkenyl-(pentafluorosulfanyl)benzenes through Horner–Wadsworth–Emmons reaction

• George Iakobson and
• Petr Beier

Beilstein J. Org. Chem. 2012, 8, 1185–1190, doi:10.3762/bjoc.8.131

• substitution reaction of meta- and para-nitro-(pentafluorosulfanyl)benzenes and diethyl chloromethylphosphonate, undergo Horner–Wadsworth–Emmons reaction with aldehydes in the presence of potassium hydroxide in acetonitrile at ambient temperature to give (E)-2-nitro-1-alkenyl-(pentafluorosulfanyl)benzenes in

Azobenzene dye-coupled quadruply hydrogen-bonding modules as colorimetric indicators for supramolecular interactions

• Yagang Zhang and
• Steven C. Zimmerman

Beilstein J. Org. Chem. 2012, 8, 486–495, doi:10.3762/bjoc.8.55

• , the ability to synthesize these recognition units containing azobenzene units opens up the possibility to turn hydrogen bonding on and off. With regard to synthesis, aromatic azo compounds are commonly prepared by an electrophilic substitution reaction, the best partners being an electron-rich

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• ] However, the C2-selectivity observed in the presence of Cu(I) salts as cocatalyst, or used alone, was suspected to arise from a proton–metal exchange of the most acidic position leading to an organocopper intermediate suitable for a nucleophilic substitution reaction. Daugulis reported a first