The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• is also dependent on the kind of coupling compound used [31]. For example, phenols are successfully coupled in alkaline conditions in which the phenolate ion is formed. These conditions provide the desired electron-releasing group thus facilitating the electrophilic substitution reaction to afford

Methylpalladium complexes with pyrimidine-functionalized N-heterocyclic carbene ligands

• Dirk Meyer and
• Thomas Strassner

Beilstein J. Org. Chem. 2016, 12, 1557–1565, doi:10.3762/bjoc.12.150

• should be active according to the proposed catalytic cycle, which starts with an electrophilic substitution reaction. We therefore set out to synthesize the corresponding methyl complexes for the “hybrid ligand” with chloro- and trifluoroacetato ligands. Results and Discussion Synthesis Some time ago we

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

• of ferrocenyl carbene complexes has been extensively investigated [25][26][27][34][35][36][37][38][39]. A second ferrocenyl unit can be incorporated by employing aminoferrocene (Fc-NH2) [40][41] in a nucleophilic substitution reaction [27]. The trimetallic complex Cr(CO)5(E-2) with the

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• substitution reaction on C-iodo product 24 from the adjacent aryl group (Scheme 8). Thus, the possibilty of the addition at the 2-position of electron-rich N-acylated aniline 3a to the tertiary iodide intermediate was also investigated. Towards this, we thought of synthesizing the C-iodo intermediate using N

• 4a in 80–85% yield when the reaction was carried out at elevated temperature (Scheme 8). We thought there could be the possibility of a substitution reaction of iodide compound 24 prepared in-situ to form directly 2-oxindole 4a under elevated temperature. Thus, it was decided to carry out the C

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• , Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany 10.3762/bjoc.12.107 Abstract The design, development and application of an efficient procedure for the concise synthesis of the 1,3-syn- and anti-tetrahydropyrimidine cores of manzacidins are reported. The intramolecular allylic substitution reaction of a

• allylic substitution reaction of a joint precursor 5. Subsequently this strategy is successfully applied to the synthesis of the authentic pyrimidine cores 3 and 4 of manzacidin A (1) and ent-manzacidin C (2). Results and Discussion General synthetic concept As part of our ongoing efforts to the design of

• groups [38][39][40][41][42][43], is based on a sequential nucleophilic addition and an intramolecular allylic substitution reaction. It relies on the coupling of different homoallylic nucleophiles of general type 6 to diverse electrophiles 7 such as Michael acceptors, or heteroolefins as for example

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• studied their ability to undergo an ‘allylic halide for allylic nitrate’ substitution reaction which we demonstrate generates (E)- and (Z)-3-methyl-4-hydroxybut-2-enyl nitrate, and (E)- and (Z)-2-methyl-4-hydroxybut-2-enyl nitrates (‘isoprene nitrates’) in 66–80% overall yields. Using NOESY experiments

• our protocol proceeds via the application of Horner–Wadsworth–Emmons Chemistry that generates readily functionalized motifs that undergo an all but previously non-existent, allylic ‘halide for nitrate’ substitution reaction. A consequence of the broader importance of organic nitrates we envisage our

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• -catalyzed allylation substitution reaction of oxazol-4(5H)-ones and thiazol-4(5H)-ones to afford enantioenriched tertiary alcohols and thioethers (Scheme 19) [42]. In this case the diastereoselectivity is controlled by cations, in contrast to most of the described protocols wherein it is modulated by anions

Aluminacyclopentanes in the synthesis of 3-substituted phospholanes and α,ω-bisphospholanes

• Vladimir A. D’yakonov,
• Alevtina L. Makhamatkhanova,
• Rina A. Agliullina,
• Leisan K. Dilmukhametova,
• Tat’yana V. Tyumkina and
• Usein M. Dzhemilev

Beilstein J. Org. Chem. 2016, 12, 406–412, doi:10.3762/bjoc.12.43

• (Scheme 5). Thus bisaluminacyclopentane 9a, synthesized by catalytic cycloalumination of 1,7-octadiene, was subjected without isolation to the substitution reaction with aryl(alkyl)dichlorophosphine with replacement of Al by Р (ca. 20 °С, 30 min) to give bisphospholane 10a as a mixture of isomers in a

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• substitution reaction in a one-pot manner. Methyl iodobenzoates were introduced following this approach (Scheme 7, 33a,b), unfortunately, degradation occurred during the final oxidation step to obtain the α-nucleophile group [87]. The 3-monosubstituted derivative 41 was successfully obtained starting from the

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

•  1, path a). Bromoallyl sulfones 2a,b partake in a cesium carbonate-mediated formal vinylic substitution reaction with heteronucleophiles to afford valuable multifunctional building blocks [23]. For example, the reaction of 2a with 4-chlorophenol afforded the enol ether 3 in 84% yield (Scheme 1, path

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• ’ regioselectivity, creating a new stereogenic center [59][60]. In 1995, Bäckvall et al. reported the first example of an asymmetric allylic substitution reaction catalyzed by a chiral copper complex, giving a moderate enantioselectivity (42% ee) in Grignard reactions with allylic acetates. The enantiomeric excess

• protocol was demonstrated by the concise enantioselective syntheses of the Pummerer ketone (Scheme 27) [67]. In 2012, Sawamura et al. reported a Cu(I)-DTBM-SEGPHOS-catalyzed enantioselective allylic substitution reaction with alkylboron compounds [68]. In this report, alkyl-9-BBN reagents for the first

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• electrophilic substitution reaction, the occurrence of powerful new synthetic strategies such as transition metal-catalyzed C–H activation brought new opportunities to the synthesis of more diversely halogenated products by enabling the halogenation of more challenging substrates by more selective

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• step. An analytically pure sample of 3 was obtained by additional column chromatography. In order to increase the yield of azide 3 by replacing 3-O-mesylate 2 with the corresponding 3-O-triflate in the nucleophilic substitution reaction with sodium azide, the O-protected mannitol derivative 1 was

Ruthenium indenylidene “1^st generation” olefin metathesis catalysts containing triisopropyl phosphite

• Stefano Guidone,
• Fady Nahra,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2015, 11, 1520–1527, doi:10.3762/bjoc.11.166

• (OiPr)3. Full conversion of the starting material was observed affording complex 2 (Scheme 2). Unfortunately, all attempts to purify 2 failed due to the presence of PCy3 decomposition products. The PPh3 adduct Ind-I0 was then employed as alternative starting material for the ligand substitution reaction

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic acids using benzoic anhydrides and thiourea

• Mohammad Abbasi and
• Reza Khalifeh

Beilstein J. Org. Chem. 2015, 11, 1265–1273, doi:10.3762/bjoc.11.141

• [51] or thioacetamide [52], a benzoic anhydride undergoes a nucleophilic acyl substitution reaction with thiourea to produce the corresponding S-benzoylisothiouronium salt as an intermediate. After addition of H2O to the reaction mixture, the salt is hydrolyzed by the hydroxide anion to generate the

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