Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• % de), the utility of this procedure was demonstrated by converting the minor (S,S)-diastereomer 6 into the orthogonally protected γ-hydroxylysine derivative 7 which is found in the potent antitumor agent glidobactin A [19]. Another chiral electrophile, such as aldehyde 8 prepared in five steps from

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• moiety as monodentate hydrogen bond donor to activate the electrophile (anhydride), whilst retaining the tertiary amine functionality to activate the nucleophile (alcohol, Figure 2). As part of our ongoing research program on chloramphenicol base organocatalysis, herein, we report a new class of

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• to quinoline can be considered as an umpolung of the Skraup quinoline synthesis since it uses reversed polarity of reagents, where the C=C–NO2 fragment of the nitroarene is the electrophile reacting with an arylmethyl carbanion, the nucleophile (Scheme 2). Recently, we used the reactions of

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• with methylmagnesium bromide [17], and direct methylation using radical reactions [9][18][19]. Hence, we searched for a more viable method for the introduction of the methyl group. A prerequisite was that the organometallic intermediate should be trapped by an electrophile which could later be

• transformed into a methyl group, but the trapping product should be easily separable from the starting material 3. For this purpose we selected Eschenmoser’s salt (N,N-dimethylmethyleniminium iodide) as an electrophile. Trapping of the metalated species was expected to give the N,N-dimethylaminomethyl

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• explore the stereointegrity of the aforementioned reactions using enantiopure 7-[2H1]-(R)-benzyl fluoride ((R)-1, Figure 2) as a primary, yet chiral electrophile [10]. Substitution reactions of benzyl fluoride (1) will generate substituted products that retain the deuterium atom, and the degree of

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

• ][12][13] with leaving groups, thus switching to an electrophile [14][15][16], or convert to an α-radical carbon with an oxidant [17][18][19]. β-Ketoesters are also inexpensive, abundant and commercially available, making them attractive substrates. In our continuing effort to develop green and atom

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

• produce thiophenes 4 through an ordinary N–H insertion process [6][7][8][9][10][11][12][13] (Scheme 5). To the best of our knowledge, the discovered processes are the first examples of intramolecular reactions of thiocarbonyl ylides with cyano groups, acting as an electrophile, with subsequent 1,3

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• equivalent of C1-electrophile: R2COOH/T3P® [15], BrCN (R2 = NH2) [16], ArNCS/DCC (R2 = NHAr) [20]. Heterocyclization of 1-aminoimidazoles with 1,3-dicarbonyl or α,β-unsaturated carbonyl compounds (route B). Conditions: i) R1 = NH2, NHAlk, R2 = Ph, R3,4 = Alk, Ar, solvent-free [24], AcOH [25][26], R3 = Ph, R4

One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni’s reagent

• Azim Ziyaei Halimehjani,
• Martin Dračínský and
• Petr Beier

Beilstein J. Org. Chem. 2017, 13, 2502–2508, doi:10.3762/bjoc.13.247

• dithiocarbamates via a one-pot reaction of an amine, CS2 and an electrophile is of great interest due to its simplicity and environmental friendly procedure. Diverse electrophiles including alkyl halides [18], epoxides [19], alkenes [20][21][22], aldehydes [23], and alcohols [24] were applied for the synthesis of

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• orbital. In our case, possible electron donation is expected either by the σC-C in TS(pro-R,si) or σC-CF3 in TS(pro-R,re). Because the former orbital is more electron-rich, imines as electrophiles should approach from the si face of the pro-R enolate (E: an appropriate electrophile in Scheme 1). The same

• orbital interaction would be operative when the electrophile came closer from the re face of the pro-S enolate which suffered from the existence of the sterically demanding iPr group. As a result, the major reaction pathway was considered to follow the transition state TS(pro-R,si) where the si face of

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

• contact with water, but does not undergo comparable side reactions with Ti(OiPr)4 or AlMe3. Sulfinylimine 5l appears to be a weaker electrophile, which is attributed to the lower electronegativity of Cl compared to F and to the larger size of the CCl3 group compared to the CF3 moiety, sterically shielding

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

• glycosylation has been proposed (Scheme 15). Addition of p-TolSCl to the mixture of donor 76 and AgOTf forms p-TolSOTf, a powerful electrophile that can electrophilically add to the anomeric sulfur atom of 76 forming disulfonium ion 77 (step 1 in Scheme 15). After ejection of the ditolyl disulfide, 77 can

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

• –Hillman reaction The Morita–Baylis–Hillman reaction (MBH) employs olefins, tertiary amine catalysts and electrophile aldehydes to produce multifunctional products. Mack et al., found a significant enhancement in the rate of a Morita–Baylis–Hillman (MBH) reaction under ball milling conditions (Scheme 5

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• enolate and subsequent asymmetric α-functionalization with an electrophile (E). Reported asymmetric α-fluorination of β-ketoesters 1 using different chiral PTCs. Asymmetric α-fluorination of benzofuranones 4 with phosphonium salt PTC F1. Asymmetric α-fluorination of 1 with chiral phosphate-based catalysts

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• significantly contributed to the field of asymmetric synthesis [1][2][3][4][5][6]. In these catalysts, (thio)urea and tertiary amino functional groups cooperatively activate a nucleophile and an electrophile simultaneously, in a suitable spatial configuration. Thus, they enable various stereoselective addition

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• acceptor, with the product of the reaction termed glycoside. Examples of acceptor molecules in nature are other saccharides to form oligosaccharides, nucleobases to form nucleosides, and amino acid side chains to form glycoproteins. The donor is the electrophile in the reaction and, therefore, when

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• opinion, the observed difference in the regioselectivity of the (thio)carbamoylation and acylation of 2 may be due to different bulkiness of the reacting electrophile: the electrophilic center of the protonated iso(thio)cyanate is relatively unhindered and able to attack the electronically activated but

• sterically hindered pyrene 1-position, whereas the bulkier protonated acetyl trifluoroacetate (the postulated electrophile in the examined Friedel–Crafts acylation) attacks sterically the less hindered 4-position. Conclusion We found that triflic acid-promoted (thio)carbamoylation of 2 with aliphatic iso

Metal-free hydroarylation of the side chain carbon–carbon double bond of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles in triflic acid

• Anna S. Zalivatskaya,
• Dmitry S. Ryabukhin,
• Marina V. Tarasenko,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya,
• Elena V. Grinenko,
• Ludmila V. Osetrova,
• Eugeniy R. Kofanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2017, 13, 883–894, doi:10.3762/bjoc.13.89

• -diprotonated form D. The calculated electronic characteristics of species A–F revealed that the dication D has the highest electrophilicity index ω (7.48 eV) among the other cationic species, even including trication F (Table 1). Therefore, dication D is expected to be an extremely reactive electrophile

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• of DMAP (Figure 1D). In the first part of the suggested mechanism, the pyridine base substitutes the chloride to form a sulfonylpyridinium intermediate. This intermediate makes the sulfonyl group a better electrophile, hence, the attack of the primary amine in the second part of the mechanism becomes

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• of nanoparticle formation. Trapping of the iminium electrophile could allow oligomer formation and dehydration, leading to the formation of the sp3-enriched nanocrystalline core. In the second phase of the reaction, following the loss of bulk water, further carbonisation occurs and aromaticity is

• ., TTDDA or sugar-derived amine) or through the nucleophilic attack of an alcohol to the iminium electrophile, followed by rearrangement of the resulting imidate. The work by Mandal et al. has also recently sought to provide some insights into nanoparticle formation and PL mechanism for sugar-derived CDs

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• domino reactions of N-propargylamines 20 with isothiocyanates 21 developed by Castagnolo. Electrophile-mediated cyclization of N-propargylthioureas 55.

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• activate the terminal acetylene primarily, which then undergoes a nucleophilic addition to the iminium electrophile generated from the aldehyde and the amine. Among different transition metals, copper metal has been mostly explored as the catalyst to activate the terminal acetylene, though there is a

• this case, activation of the Csp–COOH occurs via decarboxylation followed by the coupling with an iminium electrophile to produce the propargylamine. Although the strategy is interesting, functionalized acetylene carboxylic acids are difficultly accessible and the reaction is less 'atom economic

Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• the reaction with the propyl analog 8 (50% versus 35%), but suffered from a slightly lower regioselectivity. In fact, 4% of the 3-monosubstituted regioisomer of 9 was also formed, whereas less than 1% of the 3-monofunctionalized regioisomer of 10 was observed for the reaction with electrophile 8. Once

• the first group was introduced in position 2, the substitution reaction at O-3 on the adjacent unit A was performed. Due to the lower reactivity of this alcohol group, an excess of base and electrophile was required for this step. In addition, the presence of the sterically hindered trityl-protected

• decreased the yield of scavenger 3. The introduction of the methyl iodobenzoate substituent at O-3 was conducted starting from monohydroxy compound 15 [34]. After reaction with electrophile 12, compound 4 was obtained through oxidation and hydrolysis of intermediate 16 (Scheme 2) using the same experimental

Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

• Ghina’a I. Abu Deiab,
• Mohammed H. Al-Huniti,
• I. F. Dempsey Hyatt,
• Emma E. Nagy,
• Kristen E. Gettys,
• Sommayah S. Sayed,
• Christine M. Joliat,
• Paige E. Daniel,
• Rupa M. Vummalaneni,
• Andrew T. Morehead Jr,
• Andrew L. Sargent and
• Mitchell P. Croatt

Beilstein J. Org. Chem. 2017, 13, 384–392, doi:10.3762/bjoc.13.41

• ], nitro [26][27], or alkyne [21][28][29][30][31][32], Scheme 1), or use an aryl carboxylate [33][34] which typically requires the assistance of silver or copper(I) salts for the decarboxylative step. It is rare to use a pentadienyl electrophile [35], or to have a diene or simple alkene adjacent to the

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• described in Scheme 1, the nature of the medium and the substrate strongly influence the course of the reaction. Then, in the absence of a proton source, the organolithium intermediate can cyclize or react with an electrophile giving the expected coupling products [23][24][25][26][27]. Metal dissolving