Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• be an environmentally benign method to achieve the formation of a new chemical bond and a functional group conversion by using electrons as redox reagent rather than terminal chemicals [20][21][22][23][24][25][26][27]. In this context, we have applied simple halide ions as redox catalysts to achieve

• ). Investigation of the anode proved that graphite was superior to Pt and DSA (Dimensionally Stable Anode, Table 1, entries 14 and 15). Finally, to further improve the reaction efficiency, several halide-containing mediators as redox catalyst were evaluated. To our delight, when n-Bu4NI was utilized as a redox

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• ). However, it was found that the generation of the trifluoromethyl anion proceeds faster than the subsequent transfer of CF3 to the aromatic halide. Subsequently, the problem was solved by using a slow addition mode that adjusted the rate of decarboxylation step to the rate of the consumption of CF3 in the

• groups. This reaction can tolerate a variety of functionalities, such as alkoxy, amino and halide groups. The author proposed a plausible mechanism depicted in Scheme 42. At first, a dinitrogen ligated complex (N,N)CuX A is generated in situ by the reaction of CuI with phen. Then, a copper(I)-acetylide

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

• photoexcited state of [IrIII] to [IrII] and forms a thiyl radical. Next, the [IrIII] is regenerated by single-electron reduction of the aryl halide, delivering an aryl halide radical anion. Radical addition to the aromatic thiolate anion forms a sulfide radical anion intermediate, which is oxidized by the

• base and DMSO as solvent they observed a colouring of the reaction mixture, whereas the reagents are colourless themselves. They suggest that the thiol becomes deprotonated to the respective thiolate anion and subsequently an electron donor–acceptor complex with the aryl halide is formed. Irradiation

• with white light then triggers a light-induced electron transfer from the anion to the aryl halide, releasing the halide as an anion and resulting in a thiyl radical and an aryl radical. Finally, radical–radical cross-coupling yields the respective diaryl sulfide. Ammonium thiocyanate Formation of

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• Wehman (Scheme 4) [10]. Vinylphosphonium salts can also be prepared by alkylation of phosphines (usually triphenylphosphine) with allyl halide derivatives and isomerization of allylphosphonium salts 4 thus obtained under the influence of bases such as triethylamine or sodium carbonate (Scheme 5) [11][12

• phosphorus ylides from vinylphosphonium salts. Intramolecular Wittig reaction with the use of vinylphosphonium salts. Alkylation of diphenylvinylphosphine with methyl or benzyl iodide. Methylation of isopropenyldiphenylphosphine with methyl iodide. Alkylation of phosphines with allyl halide derivatives and

Synthesis of naturally-derived macromolecules through simplified electrochemically mediated ATRP

• Paweł Chmielarz,
• Tomasz Pacześniak,
• Katarzyna Rydel-Ciszek,
• Izabela Zaborniak,
• Paulina Biedka and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2017, 13, 2466–2472, doi:10.3762/bjoc.13.243

• . As expected, addition of an alkyl halide initiator to a solution of CuIIBr2/TPMA during the voltammetric measurements causes a loss of reversibility and an increase of the cathodic current because of reduction of the regenerated CuIIBr2/TPMA via the catalytic electrochemical catalytic process (EC

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• to avoid nucleophilic substitution of the halide at a late stage, we decided to start the synthesis with 4-azidobutanal, which was prepared by opening THF with iodine and NaBH4, nucleophilic substitution by sodium azide and Swern oxidation of the alcohol. 4-Azidobutanal was converted with chiral

Comparative profiling of well-defined copper reagents and precursors for the trifluoromethylation of aryl iodides

• Peter T. Kaplan,
• Jessica A. Lloyd,
• Mason T. Chin and
• David A. Vicic

Beilstein J. Org. Chem. 2017, 13, 2297–2303, doi:10.3762/bjoc.13.225

• -fold excess of aryl halide [4]. Therefore, while yields of the SIMes-based systems can provide good yields of product, the phen-based systems remain far more practical. Ligandless CuCF3 was also tested under the reported optimized reaction conditions [15], but in our hands the protocol afforded CHCF3

• reactivity of A2 for the more electron-rich aryl halide. Moreover, an induction period was observed for both A1 and A2. We noted a detection limit of approximately 2% with our NMR spectrometer, so we believe this induction period with the electron-rich substrates is real and not stemming from the different

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• successful coupling with a particular nucleophile and for prevention of side reactions. There are several sources of α-nitrosoalkenes as shown in Scheme 1. Conventional precursors of α-nitrosoalkenes are α-halooximes 1 (or halo-substituted nitroso compounds [11][12]), which undergo deprotonation/halide

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• reaction between di-tert-butyl phosphite and either benzyl halide [137] (Michaelis–Becker reaction) or aldehyde [134] (Pudovik reaction) or using tris-tert-butyl phosphite (Abramov reaction) [135]. The elimination of the t-Bu moieties can be efficiently achieved in presence of trifluoroacetic acid (TFA

• nucleophilic halide anion is another feature of this reaction. Indeed the treatment of TMSOTf on a phosphonate did not induce the dealkylation likely due to the absence of nucleophilic species [161]. It is worth noticing that the nucleophilic attack of bromide only occurs on alkyl chains as exemplified by a

p-tert-Butylthiacalix[4]arenes functionalized by N-(4’-nitrophenyl)acetamide and N,N-diethylacetamide fragments: synthesis and binding of anionic guests

• Alena A. Vavilova and
• Ivan I. Stoikov

Beilstein J. Org. Chem. 2017, 13, 1940–1949, doi:10.3762/bjoc.13.188

• gain of the resulting complexes of the macrocycles 3 and 9 with a number of single-charged anions. It can be clearly seen that a linear dependence of the anion size on the energy difference is observed for halide anions. That is, the larger the anion size, the lower the gain in the energy of the

• results of the semi-empirical modeling are in a good agreement with spectrophotometric titration data in the case of halide ions: the efficiency of the anion binding by thiacalix[4]arenes 3 and 9 decreases in the range from F− ion to the larger I− ion (Table 4). In the case of the macrocycles 3 and 9, the

• logarithm of the association constant of the resulting complexes increases from the energy gain difference calculated using the semi-empirical PM3 method (Table 4). However, an unambiguous tendency is observed only for spherical substrates (halide ions). But there is no such dependence in the case of

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• -free Wittig reaction of organic halides with aldehydes or ketones (Scheme 6) [55]. Suzuki Coupling In 2000, Peters and co-workers first reported the palladium-catalyzed Suzuki coupling reaction under ball-milling conditions [56]. In a planetary mill for 30–60 min, the mixture of aryl halide (1.0 equiv

• ) technique for the synthesis of dialkyl carbonates [90]. Using potassium carbonate, alkyl halide and 2 equiv of phase-transfer catalyst 18-crown-6 yielded dialkyl carbonate in 74%. However, in absence of 18-crown-6 the yield was only 2% at 17 h (Scheme 20). Transesterification is a synthetic approach mostly

• ]. Mechanochemical Pd-catalyzed C–H activation [185]. Mechanochemical Csp2–H bond amidation using Rh catalyst. Mechanochemical synthesis of indoles using Rh catalyst [187]. Mizoroki–Heck reaction of aminoacrylates with aryl halide in a ball-mill [58]. IBX under mechanomilling conditions [8]. Thiocarbamoylation of

Ni nanoparticles on RGO as reusable heterogeneous catalyst: effect of Ni particle size and intermediate composite structures in C–S cross-coupling reaction

• Debasish Sengupta,
• Koushik Bhowmik,
• Goutam De and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 1796–1806, doi:10.3762/bjoc.13.174

• with comparable conversions (Table 1, entry 15). We then extended the optimized reaction conditions (as in Table 1, entry 4) using Ni/RGO-40 to diverse functionalized aryl halide/thiol combinations. The results are indeed encouraging and summarized in Table 2. Both coupling partners, i.e., the

• ) species, which then undergoes oxidative addition to the aryl halide forming a Ni(III) species, as proposed previously [19]. Conclusion In conclusion, we have shown that a RGO-supported Ni(0) nanocomposite (Ni/RGO-40) with average size (≈11–12 nm) Ni NPs display high catalytic efficiency for C–S cross

• /RGO-40 A mixture of aryl halide (1 mmol), thiol (1.2 mmol), potassium carbonate (1.2 mmol), Ni/RGO-40 catalyst (22 mg; Ni content is 8.8 mg, 0.15 mmol, 15 mol %) in DMF (3 mL) were taken in a 15 mL sealed tube, flashed and filled with N2 gas and quickly screw-capped. The reaction mixture was then

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• alkyl halides, however, the conditions had to be optimized for each substrate. In particular, reactions carried out by a one-pot, two-step process [28] of 1 with K2CO3 (producing in situ the potassium imide salt), followed by the addition of the halide and further milling in conjunction with LAG (DMF

• physical state of the halide reagents (either liquid or solid alkyl halides) did not influence the reaction outcome (see Supporting Information File 1, Table S1). Further alkylation experiments were carried out with selected imides 11–17 (Figure 1, Table 3). The sequential mechanochemical alkylation was

• the ratio of the alkyl halide reagent at two equivalents, ball milling afforded mainly the targeted mono-alkylated product 28 (Table 3, entry 9). The regioselectivity of substrates with two nitrogen-sites available for alkylation could be also controlled by reagent ratio or choice of the alkyl halide

An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation

• Carolina S. García,
• Paula M. Uberman and
• Sandra E. Martín

Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166

• with a magnetic stirring bar, aryl halide 1a–h (0.25 mmol), K2CO3 (0.5 mmol), olefin 2a–d (0.3 mmol), ethanol (0.5 mL) and water (to obtain a total volume of 2 mL taking into account the volume of Pd NPs solution) were added. Finally, the required volume of the Pd NPs dispersion was added. Then, the

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• oxindoles in this transformation with nitroolefins (Scheme 2). In general, the diverse 3-substituted oxindoles 1a–j with electron-donating, electron-withdrawing, or halide groups could undergo a smooth reaction with nitrovinylacetamide (2a) in moderate yields, good diastereoselectivity, and general

Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols

• Chandra Kant Maurya,
• Avik Mazumder and
• Pradeep Kumar Gupta

Beilstein J. Org. Chem. 2017, 13, 1184–1188, doi:10.3762/bjoc.13.117

• order to further study the scope and limitations of the method, different thiocyanates were treated with P2S5 in refluxing toluene to get the corresponding thiols in good to moderate yield in short reaction time (Table 2). The thiocyanate substrates were prepared by the reaction of alkyl halide with

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• . Notably, they had to switch the halide/organometallic functionality of each building block after an unsuccessful coupling between the stannane synthesized by reduction and methylation of ketone 67 and the iodine derived from fragment 62. They assume that the steric hindrance of the methyl group in C10

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• pharmacological evaluations support the notion that the key pharmacophores of DHβE are located in the A and B rings. Keywords: DhβE; Mizoroki–Heck cross-coupling reaction; 6π-electrocyclization; [6,6]-bicyclic lactone; vinyl halide; Introduction The neuronal nicotinic acetylcholine receptors (nAChRs) have been

• the C ring by an intramolecular Mizoroki–Heck cross-coupling reaction from a Z-configured olefin which would be crucial to the stereochemical outcome of the Heck cyclization event. We envisioned a Z-stereoselective synthesis of a vinyl halide [17] which should secure the desired E-stereochemistry for

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• presence of Pd and Cu catalysts to afford (E)-α-selenylstannanes for the synthesis of trisubstituted alkenes [13] and hydrozirconation with further replacement of Zr atom by hydrogen or halogen [14] or their use in the preparation of α-seleno-α,β-unsaturated ketones [15]. Besides, hydrogen halide-addition

• three-step one-pot procedure using KSeCN (2), alkyl (3) and styryl halides (4) with good yields (Scheme 1, A) [38]. This reaction proceeds through an initial nucleophilic substitution reaction between the alkyl halide and KSeCN to afford the corresponding alkyl selenocyanate (RSeCN). The treatment of

• the latter with K3PO4 generates the alkyl selenolate anion (RSe−) which reacts with another RSeCN molecule to give the corresponding diselenide R2Se2. Reduction of the latter diselenide by treatment with NaBH4 affords an alkyl selenolate anion, which reacts with styryl halide to give the desired

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• selectivity towards these compounds increased with the excess of phenylzinc halide. In a model reaction employing 3b and 2 equivalents of PhZnBr, a mixture of 7b (48%), the desired coupling product 6b (27%) and dehalogenation product 2b (25%) was isolated. Such homocoupling and dehalogenation processes have

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• , mild reaction conditions, and easy access to starting materials. 1.1 Aryl halide as substrate Compared with other traditional starting materials, such as phenylsulfonic acid, aryl ketone and phenylboronic acid [17][18][19][20], aryl halides can be considered as simple and economical starting materials

• : In 2006, Buchwald and co-workers described the first synthesis of phenols from aryl halides through a palladium-catalyzed reaction [21]. The C–O coupling reaction of an aryl halide and potassium hydroxide took place when using Pd2dba3 as catalyst, biphenylphosphine (L1 or the bulkier L2) as ligand

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• different aryl halide (Ar2X). Without requiring the protection of sensitive functionalities, running the flow system using a residence time (tR) of about 4.7 min at a temperature above 100 °C, high yields of coupling products were obtained. Noteworthy, the Suzuki–Miyaura coupling did not require the use of

Highly reactive, liquid diacrylamides via synergistic combination of spatially arranged curing moieties

• Maximilian Maier,
• Magnus S. Schmidt,
• Markus Ringwald and
• Christoph P. Fik

Beilstein J. Org. Chem. 2017, 13, 372–383, doi:10.3762/bjoc.13.40

• synthesis of 12 and other similar derivatives through a multistep reaction with the final step comprising the treatment of N,N'-dipropylperhydropyridazine-3,6-dione with a borane solution in THF [31]. Considering the high reactivity of 7 and the assumption, that the allylic double bond to the halide is

(Z)-Selective Takai olefination of salicylaldehydes

• Stephen M. Geddis,
• Caroline E. Hagerman,
• Warren R. J. D. Galloway,
• Hannah F. Sore,
• Jonathan M. Goodman and
• David R. Spring

Beilstein J. Org. Chem. 2017, 13, 323–328, doi:10.3762/bjoc.13.35

• state 5 containing two chromium ions bridged by a halogen. The less sterically hindered equatorial positions are occupied by the aldehyde substituent (R1 in Scheme 2) of 1 and halide group (X) of 3 and the aldehyde oxygen is thought to be coordinated to one of the Cr centres (the “coordinating” Cr

Efficient access to β-vinylporphyrin derivatives via palladium cross coupling of β-bromoporphyrins with N-tosylhydrazones

• Vinicius R. Campos,
• Ana T. P. C. Gomes,
• Anna C. Cunha,
• Maria da Graça P. M. S. Neves,
• Vitor F. Ferreira and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2017, 13, 195–202, doi:10.3762/bjoc.13.22

• biological properties or might become important templates for further functionalization procedures (Scheme 2). Results and Discussion For this work 2-bromo-5,10,15,20-tetraphenylporphyrinatozinc(II) (1) was used as the aryl halide and also the easily accessible N-tosylhydrazones 2a–c (Scheme 3). Both

• substrates were prepared by following literature procedures; the halide partner by controlled bromination of 5,10,15,20-tetraphenylporphyrin (TPP) with N-bromosuccinimide followed by metallation with Zn(AcO)2 [31][32] and the tosylhydrazones 2a–c by reaction of the adequate ketones with tosylhydrazines [33