Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• convenient route to fluorinated phthalides from 2-cyanobenzaldehyde or 2-formylbenzoates in a one-pot manner. In the transformations, installation of fluorinated substituents at the C3-position of phthalides has been achieved. The issue of the low stereoselectivity of the catalytic asymmetric

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• microfluidic conditions applied by the authors ensured even better stereoselectivity and higher yields [21]. Sequential protective group manipulation and N-acylation procedure furnished the lipid A precursor 37. The isopropylidene and anomeric allyl groups in 37 were removed and the anomeric position in 38 was

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• acetone/water [34][59]. The high stereoselectivity during the formation of compounds 7a–q is supported by the higher stability of the E-isomer, as shown for other simple N-substituted benzylideneisoindolin-1-ones [12][21]. Remarkably, acidic reaction conditions induced thermal isomerization of compounds

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• final product increased. Cyclic olefins and dienes proved to be more problematic substrates because they raised stereoselectivity issues and afforded poor yields. As for the mechanism, the reaction followed a similar pathway as the one proposed by the same group for the trifluoromethylation of silyl

• range of alkenes [28]. Thus, allylbenzene derivatives carrying diverse substituents were successfully converted into the expected products with moderate to high yields, as well as cyclic or acyclic aliphatic alkenes (Scheme 21). Nevertheless, internal alkenes suffered from regio- and stereoselectivity

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

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

• –89% and a high stereoselectivity (Scheme 6) [14][15]. The proposed mechanism of this reaction is as described in Scheme 7 [14][15]. Oxidative addition of the vinyl triflate to the catalyst results in complex 6 that upon reductive elimination (an added phosphine) provides the vinylphosphonium salt and

• electron-rich and electron-deficient aromatic aldehydes, giving the expected vinylphosphonium salts 17 with high yields and stereoselectivity, favoring the formation of an excess of E-isomers (Table 1) [17]. 1.4. Electrochemical oxidative addition of triphenylphosphine to cycloalkenes Another effective

• yield of 68–94% and in a good stereoselectivity. The configuration of products depended on the nature of the substituent in the phenyl group of the aldehyde. Electron-donating substituents favored the formation of E-isomers, while the presence of electron-withdrawing substituents made the formation of Z

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• )-monofluoroalkenes (Scheme 6) [32][33]. HWE olefination promoted by Mg(II) of (diethoxyphosphoryl)fluoroacetic acid (25) with triisopropylsilyl-protected 2-hydroxymethylcyclopentanone 26 was realized with excellent yield and stereoselectivity. Esterification of the resulting carboxylic acid 27 into the corresponding

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• derivative 9d was synthesized from 9c in a good yield by using the general procedure for N1-PMB cleavage. Likewise, regioisomeric acids 5a,g,i and their phenyl esters 6a,g,i were reduced to the respective saturated compounds 10a–c and 11a–c. In this case a high hydrogenation cis-stereoselectivity is provided

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

• ], it provides a versatile protective group for the amine during the conversion of the alkyne. Additionally, it’s chirality indicates epimerization and, for example in the Pauson–Khand reaction [14], allows the determination of the stereoselectivity of asymmetric conversions by simple 1H NMR experiments

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• fluorination based on hydroxy–fluorine interconversion seems to be an eloquent, simple and efficient procedure for the creation of a certain fluorinated organic molecule, regio- and stereoselectivity, stereocontrol and substrate influence remain a challenge in the case of highly functionalized frameworks

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• of being able to generate amino acids of different backbone lengths (e.g., 5, 6, Figure 1) via a unified strategy; (ii) an ability to access any stereoisomer of the target molecules (provided that the stereoselectivity in each fluorination step was catalyst-controlled); (iii) the lower toxicity of

• afforded the syn,anti-epoxy alcohol 28b with good stereoselectivity, albeit in poor yield. One reason for the low yield of 28b was the difficulty in its chromatographic separation from the byproducts of the epoxidation reaction. Nevertheless, a sufficient quantity of 28b was obtained to proceed some way

• with the synthesis. Compound 28b was treated with DeoxoFluor at low temperature, in order to affect a deoxyfluorination of the benzylic alcohol. This reaction gave the product 31 in high yield, but unfortunately with poor stereoselectivity, presumably due to a competing SN1-type reaction mechanism [36

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• ethene, the reaction occurs stereoselectively or with loss of the stereochemical arrangement of substituents. For example, 4-methoxystyrene (20) reacts with E-1b in 2,5-dimethyltetrahydrofuran in the presence of ZnCl2 with complete stereoselectivity and the cyclobutane derivative 21 is formed as the sole

• [2 + 3]-cycloadduct of the intermediate thiocarbonyl S-methanide onto the C=C bond was obtained. The reaction was reported to occur with complete stereoselectivity [37]. Thermally generated azomethine ylides 32, from 1,2,3-trisubstituted aziridines 33, were tested in [3 + 2]-cycloadditions with E

• - and Z-1b, and depending on the substitution pattern of the aziridine ring, the formation of the pyrrolidine derivative 34 occurred either with complete stereoselectivity or mixtures of isomeric products were obtained. The [3 + 2]-cycloaddition of the azomethine ylide E,Z-32a, formed via conrotatory

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

• strategy shown in Scheme 6 [28]. This general synthetic scheme opens access to a variety of substituted bicyclo[2.2.1]heptanes 16 via cyclization of α-chlorooxime TBS ethers 15 as shown in Scheme 7. The stereoselectivity of Michael additions to conjugated nitrosoalkenes is an important issue considering

• the potential use of this strategy in the synthesis of natural products. Weinreb and co-workers performed a comprehensive investigation of the stereoselectivity of the conjugate addition to α-nitrosoalkenes using both cyclic [29] and acyclic substrates [30]. They have demonstrated that the

• nucleophilic addition of C-substituted malonic esters 17 to 4-tert-butylnitrosocyclohexene NSA3 (generated either from TBS ether 18 or free oxime 19) proceeds with high stereoselectivity and affords mainly or exclusively the trans-isomers of adducts 20 (Scheme 8) [29]. Expectedly, the stereoselectivity of the

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• . Subsequently, the mechanocoupling of hindered proline amino acid derivatives was developed to provide proline–proline dipeptides under solvent-free conditions. A deprotection–cyclization sequence yielded the corresponding diketopiperazines that were obtained with a high stereoselectivity which could be

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• glycosylation reactions wherein the facial stereoselectivity is achieved by tethering of the glycosyl donor and acceptor counterparts. Keywords: carbohydrates; glycosylation; intramolecular reactions; oligosaccharides; Introduction With recent advances in glycomics [1][2], we now know that half of the

• despite of significant advances. Common intermolecular glycosylation reactions in the absence of a participating auxiliary typically proceed with poor stereoselectivity. In these systems, there are no forces that are able to direct the glycosyl acceptor attack on the activated glycosyl donor that exists

• disaccharide 9 in 74% as a pure 1,2-trans isomer [52]. Expansion of this approach to other positions and sugar series showed that the stereoselectivity could be relaxed, and seemed to be dependent of the donor–acceptor match–mismatch. Thus, when succinoyl was attached to the 6-OH of the galactosyl acceptor

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• reaction of perbenzylated donor 12 in dichloromethane at −78 °C afforded the disaccharide with excellent yield but low stereoselectivity. The α/β ratio, determined by supercritical fluid chromatography (SFC), shifted significantly toward the α-isomer with ether [44] and toward the β-isomer when

• acetonitrile [45] was used as co-solvent. With all these donors, the α-stereoselectivity increased at higher temperature [46]. Donor 13, containing a remote participating group, produced the disaccharide with better α-selectivity [22][42]. Automated glycan assembly is the most rapid means to access complex

• stereoselectivity of the reactions follows reported trends. This promoter system was successfully used for automated glycan assembly. DBDMH as promotor for automated glycan assembly. Modules: a) acidic wash; b) glycosylation using DBDMH/TMSOTf, 8; c) Fmoc deprotection. Hydrolysis of glycosyl selenide 17 with DBDMH

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

• within 30 min (Scheme 4). Excellent stereoselectivity was also achieved with a diastereomeric ratio of 98:2 and enantiomeric ratio up to 99:1. Simple flash column chromatographic purification methods, low catalyst loading, gram scale synthesis, etc. were advantageous for the reaction [52]. Morita–Baylis

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• ), showed the highest selectivity and could also be recycled by centrifugation and reused with little loss in stereoselectivity after four consecutive cycles [10]. Besides the above stated, one additional advantage of mechanochemistry includes the possibility to overcome solubility restrictions in chemical

Conformational impact of structural modifications in 2-fluorocyclohexanone

• Francisco A. Martins,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2017, 13, 1781–1787, doi:10.3762/bjoc.13.172

• gauche effect, but this did not appear, because of a predominant σC–H2 → π*C=O interaction in the equatorial conformer. The conformational induction through simple structural modifications can play an important role in the stereoselectivity of reactions (kinetically dependent on the conformation of the

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Phenylsilane as an effective desulfinylation reagent

• Wanda H. Midura,
• Aneta Rzewnicka and
• Jerzy A. Krysiak

Beilstein J. Org. Chem. 2017, 13, 1513–1517, doi:10.3762/bjoc.13.150

• applied successfully to the conversion of sulfinyl-substituted cyclopropylcarboxylates into the corresponding alcohols. The presence of sulfinyl substituents in the α-position to the carboxylate group caused a desulfinylation product formation with full regio- and stereoselectivity, instead of a carbonyl

• a continuation of our studies on asymmetric cyclopropanation of vinyl phosphonates using (S)-dimethylsulfonium(p-tolylsulfinyl)methylide and its further application. It was formed as a single diastereomer with full stereoselectivity. To determine the relative configuration of the obtained structure

• phenylsilane utilizing the procedure described above and afforded phenylacetate 8 as the only product. Methylation of 9 afforded product 10 with full stereoselectivity as the only diastereomer although the configuration of this center was not determined. Also in this case treatment with PhSiH3/KOH caused a

Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

• Yoko Hamada,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 1507–1512, doi:10.3762/bjoc.13.149

• proton shift was published by using the bicyclic guanidine-type base, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), as a catalyst. In spite of these two preceding studies, we have also succeeded in attaining a similar level of chemical yields as well as stereoselectivity to the latter process by using far

Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

• Ildikó Bacsa,
• Rebeka Jójárt,
• János Wölfling,
• Gyula Schneider,
• Bianka Edina Herman,
• Mihály Szécsi and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2017, 13, 1303–1309, doi:10.3762/bjoc.13.126

• semihydrogenation of different arylacetylenes using Pd(OAc)2 or Pd(PPh3)2Cl2 as the catalyst and DMF/KOH as a hydrogen source, under conventional heating [30]. The first catalyst afforded cis-alkenes in high yields with excellent chemo- and stereoselectivity. The latter catalyst displayed lower catalytic activity

• and stereoselectivity. The stereoselectivity of the semihydrogenation process may play a crucial role concerning the biological activity of the resulting alkenes, since geometrical isomers may possess different biological functions [31]. Here we performed the partial saturation of compounds 8c–11c by

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

• of this chemistry is its ability to provide 1,2-cis glycosides with good stereoselectivity, as these glycosides still remain among the most challenging stereoisomers to synthesize as C2 neighboring group participation is not possible [40]. In fact, the access to 1,2-cis glycosides is considered a

• worked well with not only simple aliphatic and phenolic alcohols but also with amino acids and steroid alcohols (Figure 1). The authors posit that the stereoselectivity can be rationalized by an oxycarbenium/BF3-coordinated 3-bromo-2-pyridyloxy ion-pair intermediate that is displaced by the alcohol in an

• 1-O-phosphofuranosyl hexoses in good to excellent yield (Table 1, entries 1–4) [43]. The conditions provided only a very modest stereoselectivity, however, the α anomer was slightly favored regardless of the stereochemistry of the sugar at C2. Most importantly, very little or no ring expansion to

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

• stereoselective elimination and decarboxylation in situ. The corresponding aldehyde 22 was then homologated by an Abiko–Masamune anti-aldol addition [74] with ephedrine-derived ester 23, which proceeded with excellent yield and stereoselectivity. However, the subsequent removal of the sterically hindered chiral

• the aldehyde 32 with DIBALH. Finally, a Brown crotylation [77] set the two vicinal stereogenic centers of 6 with high stereoselectivity. In total this route enabled an efficient and reliable access to this key fragment. However, one drawback of this sequence was a tendency of epimerisation at C1

• lithium dimethylcuprate. In comparison with the likewise attempted Stork–Zhao olefination this protocol by Tanino and Miyashita was superior in yield and stereoselectivity [80]. To complete the fragment synthesis the [Ru]-catalyzed Trost–Alder-ene reaction [81] generated the desired primary alcohol which