Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• derivatives, from the same source of chirality. Results and Discussion Synthesis of vancosamine and saccharosamine glycals. The chiral (−)-lactic methyl ester was identified as the privileged starting material considering that the Evans aldol reaction via boron enolates [26][27][28] with an appropriately O

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• –cyclododeca[b]pyridine-3-carbonitriles 7 with ortho/ortho-para/ortho-meta substituted phenyl ring at C-4, exhibited axial chirality. For instance, in the case of 7f with p-Cl substituted phenyl ring at C-4, the 5- and 14-CH2 protons appeared as triplets at 2.56 and 3.01 ppm, respectively. However, in 7l

• [b]pyridine-3-carbonitrile hybrid heterocycles 7 with an ortho/ortho-para/ortho-meta substituted phenyl ring at C-4 may be attributed to the axial chirality induced in these molecules due to the restricted rotation of the C–C single bond. The steric hindrance exerted between the nitrile group at C-3

• and the ortho/ortho-para/ortho-meta substitution in the phenyl ring at C-4 restricts the free rotation of the C-4–phenyl C–C single bond thereby inducing axial chirality in these molecules (representative examples, Figure 2). Interestingly in some cases this reaction afforded the unaromatized indole

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• , Poland 10.3762/bjoc.14.214 Abstract Background: Atropisomers are very interesting stereoisomers having axial chirality resulting from restricted rotation around single bonds and are found in various classes of compounds. ortho-Substituted arylpyridines are an important group of them. A regio- and

• , Tanaka presented an atropselective synthesis of axially chiral all-benzenoid biaryls by gold-catalysed intramolecular hydroarylation of alkynones to give the desired atropisomeric product with a good ee value of 70% [26]. Conventional approaches to the synthesis of biaryl compounds having axial chirality

Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• I*, Figure 1) consisting of achiral components. The combination of a macrocycle with rotational asymmetry and a directional thread with non-equivalent ends is the cause of chirality in this example (Figure 1). Interestingly, our group showed that a chiral pseudorotaxane can be generated upon

• threading a tertiary ammonium axles in a directional (non-flat) calixarene-wheel (II and II*, Figure 1) [17]. In this case the chirality is created by the directionality of the calixarene wheel in a cone conformation, which differentiates the two alkyl chains around the prochiral ammonium center. In 2010

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• the desired biologic effect in living organisms, while the other enantiomer could be inactive, cause whole other biological responses or might even have the opposite effect. Hence, for the total synthesis of natural products or pharmaceuticals it is crucial to generate chirality with high

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• in biologically active molecules. This reaction was included due to the ability to introduce chirality into lead structures, something that is valuable in medicinal chemistry. The straightforward synthesis of isoxazoline 29a from the corresponding vinyl aldehyde is a perfect example of the potential

A self-assembled photoresponsive gel consisting of chiral nanofibers

• Lei Zou,
• Dan Han,
• Zhiyi Yuan,
• Dongdong Chang and
• Xiang Ma

Beilstein J. Org. Chem. 2018, 14, 1994–2001, doi:10.3762/bjoc.14.174

• and the chirality of the nanostructures could both be adjusted by subsequent light irradiation at different wavelengths. The helical nanofiber-like morphology was verified in the internal structure of the gel. The performance of this gel was investigated by a series of methods, such as UV–vis

• absorption spectroscopy, circular dichroism, scanning electron microscopy and rheological techniques. This work provides a new method for facile synthesis of chiro-optical gels. Keywords: chirality; nanostructure; organogel; photoresponse; self-assembly; Introduction Supramolecular gels [1][2] immobilized

• and co-workers [20][21][22][23][24][25][26][27][28][29][30][31] have built a multifunctional controllable gel system, which utilized L-glutamic lipid to construct nanofibers, nanotwists, and nanotubes with the property of chirality. Azobenzene, which is structurally photosensitive, is widely chosen to

A hemicryptophane with a triple-stranded helical structure

• Augustin Long,
• Olivier Perraud,
• Erwann Jeanneau,
• Christophe Aronica,
• Jean-Pierre Dutasta and
• Alexandre Martinez

Beilstein J. Org. Chem. 2018, 14, 1885–1889, doi:10.3762/bjoc.14.162

• helical arrangement of the linkers stabilized by intramolecular hydrogen bonds between amide and amine groups. The chirality of the cyclotriveratrylene unit controls the propeller arrangement of the three aromatic rings in the opposite part of the cage. 1H NMR studies suggest that this structure is

• have previously reported that the chirality unit in the south part and the chirality of the CTV unit in the north part influence each other, suggesting that the chirality of the CTV moiety could control the helical arrangement of the linkers [12][13]. We herein report the synthesis of the

• bonding, leading to a triple helical arrangement of the linkers. The CTV unit is also found to strongly control the chirality of this triple helices since the CTV with a P (respectively M) configuration induces a Δ (respectively Λ) chirality of the propeller-like arrangement of the linkers. Results and

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• engages in double hydrogen bonding to form an 11-membered ring, resulting in the chiral helicity. The helical chirality induced in iodine(III) derivatives of 23 bearing the bislactamide motif was described for 27 with an efficient differentiation of the enantiotopic faces of the styrene substrate. This

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• solution, for example, asymmetric vs propeller (C3-symmetric) [30][36][45][46], “dendritic choreography” [47], “open-gates closed-gates” frontier rotamerism [31] and “in out” axial chirality [33]. In addition, in the targeted G-2 dendrimers (Figure 1), different connections of branches around the core

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• ][14][15][16][17][18][19][20][21]. In general, chirality can be introduced into the calixarene platform either by incorporation of a chiral group or by asymmetric placement of achiral substituents, creating chirality associated with form. This is termed inherent chirality [22]. Although chiral

• selectivity was the chiral oxazoline unit and not the inherent chirality of calixarene skeleton. Asymmetric hydrogenation Starting with distally O-dialkylated calixarene precursors, a series of BINOL-derived calix[4]arene-diphosphite ligands 40a–g were synthesized by Liu and Sandoval through phosphorylation

• the inherent chirality of calix[4]arene for α-chloroacetophenone and ortho-chloroacetophenone. The results clearly showed the effect of both denticity of ketone reactant and cooperativity between normal and inherent chirality on the selectivity. More recently, Al(III)–calix[4]arene complexes 116a–c

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• imines published since the beginning of 2015. Keywords: asymmetric synthesis; chiral 3-amino-2-oxindoles; chirality; isatin imines; nucleophilic addition; Introduction Chiral oxindoles represent an important class of products widely present in nature and exhibiting many biological activities. Among

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• rearrangement reactions add further value to this chemistry. The strategies used for the synthesis of chiral hypervalent iodine reagents include either the introduction of chirality through the attachment of chiral acids or chiral alcohols to the iodine centers by ligand exchange or are achieved by the

• introduction of axial chirality through the iodoarene backbone. A series of chiral iodine reagents are documented below (Scheme 1). In many cases chiral I(I) reagents get oxidized in situ to the hypervalent I(III) reagents and/or these chiral I(III)/I(V) reagents are used in a catalytic amount in the presence

• asymmetric oxidations were examined in 20 mol % cetyltrimethylammonium bromide (CTAB) reversed micelles [25]. Interestingly, Varvoglis et al. synthesized another new class of a chiral reagent 3 using (+)-camphor sulfonic acids as the source of chirality [26] which was used by Chen et al. for the oxidation of

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

• increase resulted from a match effect [65][66][67] of the diastereomeric ion pair formed by the chiral nucleophile, the conjugated ketone and the cinchoninium salt. Hence, in our case, the chirality of the new stereochemical center was shown to be controlled by both Michael acceptor and donor interacting

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• based on chiral phase-transfer-catalysis of the Michael addition was also reported [26]. In this context, we decided to develop a synthesis of 4-methylpregabalin from a simple and achiral starting material and build its chirality centers using asymmetric catalysis. This paper describes the synthesis of

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• Teppei Sasaki Katsuhiko Moriyama Hideo Togo Department of Chemistry, Graduate School of Science, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan Molecular Chirality Research Center, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan 10.3762/bjoc.14.22 Abstract

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

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

• based on the use of chiral substrates and enantioselective catalytic procedures. Keywords: asymmetric (aza)-Reformatsky reaction; asymmetric synthesis; chirality; diastereoselectivity; enantioselectivity; total synthesis; Introduction The Reformatsky reaction involves the formation of β

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• [5]. As nucleic acids are characterized by a dominant helical chirality and exhibit a rather small set of secondary structures, each characterized by a different polarization spectroscopy signature, they are convenient targets to monitor structural changes induced by outer stimuli. Linear dichroism

• polynucleotides, particularly in the double-stranded helix of DNA or RNA, introduces helical chirality, whereby the helical axis is almost perpendicular to the aromatic base-pair plane. In this situation, the ECD changes dramatically as a consequence of the so-called coupled oscillator or exciton coupling

• spectrum, which is by the way diagnostic for the supramolecular chirality [21][22]. Particular attention should be a paid to the UV–vis and ECD spectrum shapes and baselines as well as to an opalescence of the solution in the cuvette. An apparent positive drift of the baseline during ligand concentration

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• exhibit axial chirality [21], as has been demonstrated by 1H NMR spectroscopy using the optically active shift reagent Eu(hfc)3 [19]. The enantiomers of the dicarboxylic acid 11 have been separated by flash chromatography of their diastereomeric salts with 1-phenethylamine, and the structures of the acids

• was achieved by fractional crystallization [24]. Chirality of the bisdioxine dicarbaldehyde, 2,6,9-trioxabicyclo[3.3.l]nona-3,7-diene-4,8-dicarbaldehyde, obtained by extrusion of water from triformylmethane, has also been demonstrated [25], and X-ray crystallography confirmed the structure of this

• [29]. It should be noted that both the bisdioxines [19] and the tetraoxaadamantanes [29] exhibit axial chirality as confirmed by 1H NMR spectroscopy with the Eu(hfc)3 chiral shift reagent. Bisdioxine oxime and hydrazine derivatives 26 and 27 (Scheme 8) are formed from 3 at room temperature without the

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• a mixture of diketo-adduct 6a and a pair of enol tautomers 6b, NMR spectra in DMSO exhibited two sets of signals with relative intensities about 3:5 at 27 °C. The chirality of carbon atom C7 in compound 6a makes two methyl groups nonequivalent (δ 2.14 and 2.36 ppm, Table 2). In addition, two

• chirality of C7, the two ethoxy groups are non-equivalent. It causes splitting of the signals of CH3, CH2 and C=O groups in 1H and 13C NMR spectra of 13. Like all other diketones studied, 1,1,1-trifluoro-2,4-pentanedione gave the corresponding adduct with ANBF (Table 1, entry 9). However, all attempts to

• the chirality of carbon atom C7, the protons HA and HB of the methylene group are diastereotopic and therefore have different chemical shifts (3.34 and 3.74 ppm). The geminal protons and H7 represent a well-resolved AMX system, Figure 2. The structure of compound 15 was additionally studied using X

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• Coulomb repulsion between cationic tail groups. Considering that the polarimetric response of CDs depends on both their intrinsic chirality and on their conformational dynamism, the behaviour observed indicates that our AmCDs experience their most extensive conformational rearrangements as the first

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• occurring in host–guest complex formation processes involving calixarenes in general. This can be particularly useful, even because CAP and structurally related ligands might find various interesting applications, due to their amphiphilic character, chirality and coordination ability towards metal cations

Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts

• Jan Wallbaum and
• Daniel B. Werz

Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254

• subtle differences in the substitution pattern a modular approach for their preparation is highly desirable. A simple retrosynthetic cut of the five-membered ring delivers an amino acid methyl amide and a carbaldehyde as starting materials. Chirality is commonly introduced by the use of derivatives 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

• Supporting Information File 1). Independent on the substituent, solvent and Lewis acid used, the direction of the nucleophilic attack of (trimethylsilyl)ethynyllithium was always the same, forming the new centers of chirality of all N-sulfinyl propargylamines 7 configured as expected. As already described by

• ], 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

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

• chiral auxiliary to control the chirality of the carbon atom in α-position of the phosphorus atom as exemplified by the alkylation of the phosphonodiamide 88 (Figure 27). Furthermore, phosphonodiamide can be purified by different methods including chromatography and their transformation to phosphonic