Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations

• Koichi Mitsudo,
• Junya Yamamoto,
• Tomoya Akagi,
• Atsuhiro Yamashita,
• Masahiro Haisa,
• Kazuki Yoshioka,
• Hiroki Mandai,
• Koji Ueoka,
• Christian Hempel,
• Jun-ichi Yoshida and
• Seiji Suga

Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100

• presents the diastereoselective synthesis of disubstituted piperidine derivatives by the indirect cation pool method and the elucidation of the stereoselectivity based on both NMR analyses of the cyclic N-acyliminium ions and DFT calculations. Results and Discussion N-Acyliminium ions obtained from N-Boc

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• various functional groups (protected and free alcohols, amine, E and Z olefins, diene moiety) aimed at probing potential chemo-, regio- and stereoselectivity issues – were selected: geranyl acetate (1a), neryl acetate (1b), geraniol (1c), N-tosylgeranylamine (1d) and myrcene (1e, Figure 2). Results and

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• ; oligosaccharides; stereoselectivity; total synthesis; Introduction Complex glycans serve as attractive targets for carbohydrate-based vaccines and therapeutics [1][2][3]. Streptococcus pneumonia (SPn) has been posing a serious threat in recent times. It is a major cause of pneumonia, bacteraemia, and meningitis

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• stereochemical inversion at C3' [75]. The desired stereoselectivity for 2'-deoxy analogues was obtained when BF3·OEt2 was used. Furthermore, another route to the synthesis of C-nucleosides was demonstrated by direct addition of aryl lithium reagents to the 2'-OMe ribonolactone (Figure 11B). While the expected

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• substrates were subsequently tested using 10 mol % of this catalyst in water at room temperature. The achievement of this study was not only on the stereoselectivity of the catalysts, but also on the substrate selectivity (Table 4): the preferred substrates are water-insoluble, suggesting that the reaction

Stepwise radical cation Diels–Alder reaction via multiple pathways

• Ryo Shimizu,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 704–708, doi:10.3762/bjoc.14.59

• material is lost. Indeed, the anodic oxidation of either the Z- (1Z) or the E-form (1E) in the absence of 2,3-dimethyl-1,3-butadiene (2) led to isomerization. In other words, inversion of the configuration of the radical cation 1·+ proceeds readily, leading to a loss in stereoselectivity. The radical

• adduct 3 as an approximately cis/trans = 1:4 mixture, this should proceed via a different intermediate from the acyclic radical cation intermediate (A·+). Here, we propose the cyclic radical cation intermediate B·+ for the rearrangement, imparting stereoselectivity for the six-membered ring closure. The

Liquid-assisted grinding and ion pairing regulates percentage conversion and diastereoselectivity of the Wittig reaction under mechanochemical conditions

• Kendra Leahy Denlinger,
• Lianna Ortiz-Trankina,
• Preston Carr,
• Kingsley Benson,
• Daniel C. Waddell and
• James Mack

Beilstein J. Org. Chem. 2018, 14, 688–696, doi:10.3762/bjoc.14.57

• -assisted grinding conditions, we did not truly understand the influence of the reaction medium on the reaction. Therefore, we were interested in better understanding these observations, with the goal of increasing the overall conversion and having better control over the stereoselectivity of the product

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• previously observed in other Michael-additions involving chiral auxiliaries on the nucleophile and on the Michael acceptor [62]. As for (S)-6a, catalyst 18c bearing a bulky tert-butyl group at the benzyl para-position gave the best results in term of stereoselectivity (80% de, Table 2, entry 7). However, the

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• applicable to this catalytic transformation under the optimized reaction conditions (Scheme 2). Alkyl substituents on the ester moiety of the trifluoropyruvate were found to influence the stereoselectivity drastically. The reaction of trifluoropyruvates (1c–e) bearing sterically demanding substituents such

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

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

• high stereoselectivity of the process could be explained by to the exclusive formation of the pentacoordinated transition states A and B (Scheme 5). Indeed, steric repulsion between the auxiliary and the bulky dimethyl group prevented a Re attack through transition state B, thus forcing the system to

• diastereoselectivity (>90% de), as shown in Scheme 11. To explain the stereoselectivity of the process, the authors have proposed the six-membered transition state D (Scheme 11). Product 30 was further converted into expected chiral diamine 28 through three supplementary steps. Later in 2015, Liu et al. developed Zn

• reaction could not be extended to aliphatic imines since they led to complex mixtures. To explain the stereoselectivity of the reaction providing (3S,4R)-62a, the authors proposed transition state K arisen from coordination between zinc ions and imine nitrogen, ligand 59, and the Reformatsky reagent

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