Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• , variously substituted 6-membered heterocycles of type 9 may be obtained in a general and concise fashion. Notably, this anionic relay process may directly generate up to four new stereogenic centers and thus demonstrates a high increase in structural complexity from readily available starting materials

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• is an important tool for the synthesis of complex molecules due to the high control of enantioselectivity in the formation of stereogenic centers. This paper presents a brief review of the early issues, related mechanistic studies and recent applications on this chemistry area. Keywords: C–H

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• stereogenic centers in the shown, phenyl ring “up” configuration. If one ring pointed “in”, then the cavity was no more. I had my doubters with this reaction, and it failed miserably with benzal chloride (we fished out <5% of the desired cavitand). However, if short R groups such as methyl were avoided and

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• (Figure 1). Some examples of these properties are rigidity, disposition of the two stereogenic centers, ability of the hydroxy and amino groups to coordinate to some metals or to act as hydrogen-bond donors/acceptors, the different catalytic activity of these chemical groups and their possible

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• -unsaturated aldehydes 108, affording the desired products 110 in moderate to good yields and good to excellent stereoselectivities (Scheme 35). Recently, Wang and co-workers disclosed an asymmetric synthesis of dihydrocoumarins 113 containing adjacent stereogenic centers, utilizing the cinchona-derived

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• a striking range of molecular architectures, varying in size and complexity (Figure 1) [1][2][3][4][5]. Some terpenes sport multiple stereogenic centers and multiple carbocyclic rings. These complex hydrocarbon frameworks are derived, however, from simple precursors lacking stereogenic centers and

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• subjected to an Ugi multicomponent reaction under classical or Lewis acid-promoted conditions with diastereoselectivities ranging from moderate to good. This approach represents a step-economical path to enantiomerically pure, polyfunctionalized peptidomimetics endowed with three stereogenic centers

• . Thus, this method offers an operationally simple route to enantiomerically pure complex structures like 6, introducing up to five diversity inputs and controlling three stereogenic centers (also thanks to the final chromatography). Compounds 6 are endowed with several functionalities that can be

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• chiral copper-based catalysts has enabled high yields and enantioselectivites in the formation of nitrogen- and oxygen-containing heterocycles with α-stereogenic centers. This review highlights both the accomplishments and the future work needed in this important area. Keywords: catalysis; copper

• ; enantioselectivity; iminium ion; oxocarbenium ion; Introduction Nitrogen and oxygen heterocycles with α-stereogenic centers represent important classes of biologicially active compounds [1][2][3][4][5][6][7]. Enantioselective addition of chiral nucleophiles to imines, iminium ions, carbonyls, or oxocarbenium ions

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• stereogenic centers, derived from tartaric acid, giving the product as a single isomer in good yield (Scheme 11). Sugimura et al. [31] expanded this method by introducing chiral 1,3-diol-derived tethers into the substrates, delivering the corresponding coupling products in excellent diastereoselectivity

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• it enables in a straightforward manner the sequential generation of two or more stereogenic centers. In the last decade, various chiral copper-based catalysts were evaluated in combination with different nucleophiles and Michael acceptors, and have unambiguously demonstrated their usefulness in the

• studied on a substrate scope. As shown in Scheme 2, tertiary and quaternary stereogenic centers could be generated using this methodology leading to products 19 in moderate to good yields and ees. In 2008, Alexakis and Mauduit evaluated a series of different chiral ligands in ACA reactions involving

• (CuTC) and (R)-Binap L4, which afforded the desired final products bearing two stereogenic centers with excellent diastereoselectivies (93–97%). N-Heterocyclic carbenes (NHCs) have emerged, in these last two decades, as a powerful and versatile class of ligands, and appeared to be potent in many

The marine sponge Agelas citrina as a source of the new pyrrole–imidazole alkaloids citrinamines A–D and N-methylagelongine

• Christine Cychon,
• Ellen Lichte and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2029–2037, doi:10.3762/bjoc.11.220

• guanidine moiety). The relative configuration of the stereogenic centers C-9 and C-10 was identical as described for nagelamide B (8). In contrast to citrinamine C (3), a different connection of the monomeric units was found for citrinamine D (4). Furthermore, 3 and 4 have an additional methoxy group at C-9

Chiral Cu(II)-catalyzed enantioselective β-borylation of α,β-unsaturated nitriles in water

• Lei Zhu,
• Taku Kitanosono,
• Pengyu Xu and
• Shū Kobayashi

Beilstein J. Org. Chem. 2015, 11, 2007–2011, doi:10.3762/bjoc.11.217

• linkage can be transformed into C–O, C–N, as well as into C–C bonds, while retaining stereogenic centers [1][2][3][4]. The nitrile group can be transformed into a range of functional groups, such as amides [5], carboxylic acids [6], aldehydes [7], esters [8], alcohols [9], and amines [10

Investigation of the role of stereoelectronic effects in the conformation of piperidones by NMR spectroscopy and X-ray diffraction

• Cesar Garcias-Morales,
• David Ortegón-Reyna and
• Armando Ariza-Castolo

Beilstein J. Org. Chem. 2015, 11, 1973–1984, doi:10.3762/bjoc.11.213

• repulsion between the LPEs of the nitrogen. Although 3, 5, 6, and 8 have four stereogenic centers, however, there is a mirror plane that passes through N(3), C(9), and C(7), so these compounds do not exhibit optical activity. Compounds 4 and 7 have a methyl group on the C(1) carbon, where there is no mirror

New palladium–oxazoline complexes: Synthesis and evaluation of the optical properties and the catalytic power during the oxidation of textile dyes

• Rym Hassani,
• Mahjoub Jabli,
• Yakdhane Kacem,
• Jérôme Marrot,
• Damien Prim and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2015, 11, 1175–1186, doi:10.3762/bjoc.11.132

• structural features have been used in diverse reactions [8]. The importance of these ligands lies in the fact that the stereogenic centers are kept in close proximity to the metal and thereby having a strong and direct influence on the stereochemical course of the metal-catalyzed process. Oxazolines possess

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• configurations at the stereogenic centers. Hydrodimerization of 1 in dependence on the electrolyte composition. Hydrodimerization of 1a in dependence of temperature, conversion and cell type. Preparation of 1-aryl-2-nitroalkenes. Preparative hydrodimerization of nitroalkenes. δ-Values and multiplicities of the

Regioselective synthesis of chiral dimethyl-bis(ethylenedithio)tetrathiafulvalene sulfones

• Flavia Pop and
• Narcis Avarvari

Beilstein J. Org. Chem. 2015, 11, 1105–1111, doi:10.3762/bjoc.11.124

• by the combination of chirality with the TTF motif, a certain number of families of precursors have been reported. They possess various types of chirality, i.e., stereogenic centers, axial, planar, helical chirality, and supramolecular chirality [17][18][19][20][21]. Since methylated BEDT-TTF

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• heterocycle 10. Compound 10 was isolated as one diastereomer, but the relative configuration of its stereogenic centers was not determined. Moreover, we studied the reaction of ethyl 2-ethoxymethylidenecyanoacetate (1f) with 5-AT. It has been found that this reaction does not occur either in refluxing ethanol

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• signals for the other terminal substituents. The relative stereochemistry of the stereogenic centers at positions 3 and 4 of compound 4a was established by 1D and 2D NMR spectra. Thus, a 3J coupling constant of 11.7 Hz accounts for a trans-orientation. The NOESY experiment showed only a quite weak

• stereogenic centers at positions 4 and 12 of compound 6a was first established by analysis of the 1D and 2D NMR spectra. Thus, a 3J coupling constant of 1.9 Hz corresponds with a cis-orientation and the NOESY experiment additionally supports the proximity of this pair of protons. The structure of compound 6a

• with relative stereochemistry of stereogenic centers was finally corroborated by an X-ray diffraction study (Figure 5). The heterocycles of the polycyclic fragment adopt a chair-like conformation (the puckering parameters [29] are: S = 0.78, Θ = 32.8°, Ψ = 1.0° and S = 0.83, Θ = 38.0°, Ψ = 1.8° for the

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• isolated from a Streptomyces griseoflavus (strain W-384) fermentation broth by Zähner et al. in Tübingen, Germany and structurally identified by Zeeck et al. in Göttingen, Germany in 1989–1990 [3][4]. Once the absolute configuration of all the previously unassigned stereogenic centers in the

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• , stereogenic centers and stereoelectronic effects combine to dictate the “topology” or overall fold of a macrocycle. The structure of β-D-galactose-[13]-macrodiolide 3 [9], derived from X-ray data, originated this line of investigation. It showed that both esters and the epoxide unit are each composed of four

• this case the macrocyclic ring. In total it is the balancing of a number of small factors such as rigidification by multi-atom planar units, absolute configuration of stereogenic centers and stereoelectronic effects that dictate the observed structures. Minimum inhibitory concentrations (MICs) against

• work, however, relates the role of the exo-anomeric effect on the low-energy conformation of macrocycles linked through an anomeric center. This weak stereoelectronic effect should be listed with other factors such as ring size, multi-atom planar units, and stereogenic centers as determinants of

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• α-alkyl phosphonamide, respectively [36]. Michael reactions The application of chiral, cyclic phosphonamides such as 28c in asymmetric Michael-type reactions has proven to be a powerful tool in natural product synthesis to generate up to three contiguous stereogenic centers in a single step with a

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• approach to palladium may also be responsible for the observed decrease in the reaction rate. Based on this analysis, we rationalized that the “wrong” relative configuration of the stereogenic centers in ligands L1, L2 and L3 could be responsible for the observed marginal enantioselectivity of the

cis–trans Isomerization of silybins A and B

• Michaela Novotná,
• Radek Gažák,
• David Biedermann,
• Florent Di Meo,
• Petr Marhol,
• Marek Kuzma,
• Lucie Bednárová,
• Kateřina Fuksová,
• Patrick Trouillas and
• Vladimír Křen

Beilstein J. Org. Chem. 2014, 10, 1047–1063, doi:10.3762/bjoc.10.105

• analogues are considered to be composed of two separate π-conjugated subsystems, the 3-hydroxyflavonone moiety (with the stereogenic centers C-2 and C-3), and the 1,4-benzodioxane moiety (C-10 and C-11) (see Figure 4). In this simplification we cannot avoid the adverse effects caused by neglecting the

• effects of local perturbations on specific stereogenic centers. Thus, the interpretation of our experimental ECD spectra is mainly based on empirical comparison and correlation to those of i) the dihydroflavonols taxifolin (15) and epitaxifolin (16) isolated from Thujopsis dolobrata [16] and ii) various

• obtained by the isomerization of 1 using BF3·OEt2 in EtOAc. ECD spectrum of silybin B (1b) and its separation (in a crude approximation) into two π-conjugated moieties (3-hydroxyflavonone with stereogenic centers C-2, C-3 (in blue) and 1,4-benzodioxane with C-10,C-11) (in red) according to [2]. Synthetic

Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• (2E,4E)-4,6,8,10-tetramethyltrideca-2,4-diene (15), we had to assign the relative stereochemistry at the three stereogenic centers. Actually, we had to decide between 4 structures: syn,syn-, syn,anti-, anti,syn-, and anti,anti-configuration of the methyl groups at carbons 6, 8, and 10. Since

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• the fluorination of α-branched aldehydes [7]. During the course of our study on the enantioselective construction of such fluorinated stereogenic centers, we developed a method for the enantioselective synthesis of α-chloro-α-fluoroaldehydes via the organocatalytic α-fluorination of α-alkyl-α