Recent advances in C(sp³)–H bond functionalization via metal–carbene insertions

• Bo Wang,
• Di Qiu,
• Yan Zhang and
• Jianbo Wang

Beilstein J. Org. Chem. 2016, 12, 796–804, doi:10.3762/bjoc.12.78

• the methane C–H bond. As a result, the side reactions of the highly active metallocarbene intermediate override the C–H insertion. Zinc catalysts, which were seldom used for metal–carbene C–H insertions, have been recently explored in the C–H insertion between EDA with alkanes [45]. A detailed

• computational study of the likely intermediate suggests that it is best described as a zinc-bound carbocation rather than a zinc carbene (Scheme 12). Notably, Zn is a cheap, earth-abundant 3d metal, thus making it attractive as catalyst for C–H bond functionalization. Conclusion The intermolecular metal–carbene

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

• zinc complexes (Figure 3) as mimics of the enzyme Carbonic Anhydrase. The ligands for these complexes are notoriously difficult to work with chromatographically, but I managed to synthesize a few derivatives that not only replicated the zinc binding site, but also some of the functionality that

• ‘dangles’ above the zinc-bound water in the crystal structure of the enzyme. In addition to synthesis, the project also involved a good deal of potentiometry, and this began to teach me that synthesizing enzyme mimics was a difficult challenge of balancing the need to create functionality for the active

• Nature does. Arch critic that I am, I turned on my own research; “how can we ever expect to get the zinc-bound water in our complexes to be the strong acid it is in Carbonic Anhydrase if we’re not fully taking into account context?” Jim gave me his bemused/slightly-exasperated/are you kidding me kind of

Regioselective palladium-catalyzed ring-opening reactions of C1-substituted oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylates

• Michael Edmunds,
• Mohammed Abdul Raheem,
• Rebecca Boutin,
• Katrina Tait and
• William Tam

Beilstein J. Org. Chem. 2016, 12, 239–244, doi:10.3762/bjoc.12.25

• requirement for Et3N, zinc and high temperatures had previously been determined in related reactions (Table 1) [15]. C1-methyl-substitued oxanorbornadiene 2a was selected for the optimization study due to the ease at which it can be synthesized in larger quantities. The palladium catalysts were selected based

• % respectively (Table 1, entries 9 and 4). The Lewis acid additives gave a large range of yields (Table 1, entries 10–14). Iron and aluminium chlorides gave low yields (22%, Table 1, entry 10 and 29%, entry 11), zirconium chloride and zinc iodide gave moderate yields (47%, Table 1, entry 12 and 48%, entry 13

• ) and copper chloride and zinc chloride gave the highest yields (85%, Table 1, entry 14 and 88%, entry 4). The combination of PdCl2(PPh3)2, THF, and zinc chloride resulted in the highest conversion to the ring-opened product. Once the optimized conditions were found, 2a was reacted with a variety of

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

• in aprotic solvents such as THF at low temperature, and therefore the background, uncatalyzed reaction should not interfere. As shown in Table 1, the best results were achieved by using 1 equiv of zinc bromide (Table 1, entry 8), affording a 10:1 diastereomeric ratio and an excellent overall yield

• . Other zinc-based catalysts were less efficient, whereas most of the other tested Lewis acids failed to promote the reaction at all. The use of Lewis acids in methanol or trifluoroethanol afforded lower yields with no improvement of diastereoselection. It is worth noting that a 10:1 diastereoselectivity

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

• particular, seminal reports by the Carreira lab demonstrated that the use of stoichiometric metal acetylides was not required to achieve addition to aldehydes; catalytic Zn(OTf)2 and N-methylephedrine in combination with Et3N enabled in situ formation of chiral zinc acetylides, which underwent addition to

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• of fusion of indium (156.6 °C) and zinc (419.5 °C). The heat flow calibration was based on the value of ΔH of fusion of indium (28.62 J/g). Samples in the form of fine powders (mass range 2–5 mg) were sealed in crimped, vented aluminium pans and were heated at 10 K/min, with a sealed, empty pan as

Smart molecules for imaging, sensing and health (SMITH)

• Bradley D. Smith

Beilstein J. Org. Chem. 2015, 11, 2540–2548, doi:10.3762/bjoc.11.274

• on the cell surface during the process of apoptosis or programmed cell death. Thus, phosphatidylserine is an excellent biomarker of cell death and an attractive target for molecular imaging. We reasoned that synthetic anion receptors such as zinc dipicolylamine (ZnDPA) coordination complexes would

Diversity-oriented synthesis of analogues of the novel macrocyclic peptide FR-225497 through late stage functionalization

• Jyotiprasad Mukherjee,
• Suman Sil and
• Shital Kumar Chattopadhyay

Beilstein J. Org. Chem. 2015, 11, 2487–2492, doi:10.3762/bjoc.11.270

• of the spacer region as well as the metal-binding domain attached to a particular surface recognition part present in the class of these compounds since histone deacetylase activity has been correlated to zinc-binding ability of the 8-oxo moiety in some of such compounds [25]. Moreover, the

Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues) – precursors for dyes and drugs

• Enas M. Malik,
• Younis Baqi and
• Christa E. Müller

Beilstein J. Org. Chem. 2015, 11, 2326–2333, doi:10.3762/bjoc.11.253

• Shie et al., compound 9 was treated with sodium azide and zinc bromide under MW irradiation [62], however, the desired product 1-amino-4-bromo-2-tetrazolylanthraquinone (10, Scheme 2) could not be obtained. Following an alternative procedure, nitrile 9 was reacted with sodium azide in a mixture of N

Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors

• Morgan Hans,
• Jan Lorkowski,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252

• diazabutadiene cleanly precipitated from the reaction mixture and could be isolated in high yield by simple filtration and washing. For the critical cyclization step of IDip*·HCl, Markó et al. ingeniously took advantage of the Lewis acidity of zinc chloride to activate paraformaldehyde and of its coordinating

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• that upon acid-catalyzed hydrolysis gave glucosylamines [36]. In 1991, Danishefsky and co-workers synthesized a C1 N-linked glycooxazoline from a 1,2-anhydropyranose system in dry acetonitrile and zinc chloride as a Lewis acid [32]. Though the fused oxazolines were fully characterized, the compounds

Coupling of α,α-difluoro-substituted organozinc reagents with 1-bromoalkynes

• Artem A. Zemtsov,
• Alexander D. Volodin,
• Vitalij V. Levin,
• Marina I. Struchkova and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2015, 11, 2145–2149, doi:10.3762/bjoc.11.231

• reaction provides straightforward access to α,α-difluorinated alkynes [13][14][28][29][30][31]. Our method is based on facile zinc/copper exchange allowing for versatile couplings described for non-fluorinated organozinc compounds [32][33][34][35][36][37]. Results and Discussion Organozinc compound 2a

• tripled simply by adding 2 equiv of DMF additive (Table 1, entries 1 and 2). However, in these experiments, the reaction mixtures contained about 40% of (2,2-difluoro-2-iodoethyl)benzene (PhCH2CF2I) arising from zinc/iodine exchange between 2a and the iodoalkyne. Chloroalkyne 3a-Cl was markedly less

• reaction tolerates ester groups or TBS-protected hydroxy groups. Aromatic iodide also remains unaffected (Table 2, entry 2). As for the mechanism, we believe that the reaction starts with the zinc/copper exchange resulting in the formation of fluorinated organocopper species 5 (Scheme 2). Compound 5

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• successfully performed in six steps with an overall yield of 6.5%. The steps included an organometallic intermediate and a Negishi cross-coupling reaction characterized by a transmetalation with zinc and palladium. The benzonaphthyridinone product was transformed into a bromobenzonaphthyridine intermediate by

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• using the DFT B3LYP method in order to rationalize the experimental results. Keywords: CH acidity; indoles; iodolysis; mixed lithium–zinc bases; pyrroles; Introduction Pyrrole occurs in very important natural products such as tetrapyrrolic (linear) bilirubinoids, and (cyclic) porphyrins and corrins

• ][29][30]. In the search of bases usable at room temperature, we developed pairs of metal amides able to behave synergically in such reactions. In particular, the lithium–zinc basic mixture obtained in situ by mixing ZnCl2·TMEDA and LiTMP (TMP = 2,2,6,6-tetramethylpiperidino) in a 1 to 3 ratio [31

• ]. Herein, we report our efforts to functionalize N-arylated pyrroles and indoles through deproto-metallation using this mixed lithium–zinc base (Figure 1). We showed earlier, for related substrates, the impact of the different hydrogen acidities on the regioselectivity of the reaction [37][38][40][42][43

Synthesis and spectroscopic properties of β-triazoloporphyrin–xanthone dyads

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2015, 11, 1434–1440, doi:10.3762/bjoc.11.155

• )-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of copper(II) 2-azido-5,10,15,20-tetraphenylporphyrin or zinc(II) 2-azidomethyl-5,10,15,20-tetraphenylporphyrin with various alkyne derivatives of xanthones in DMF containing CuSO4 and ascorbic acid at 80 °C. Furthermore, these metalloporphyrins underwent

• -5,10,15,20-tetraphenylporphyrin with NaNO2 in THF in the presence of H2SO4 followed by the reaction with NaN3 [28]. The corresponding zinc(II) 2-azidomethyl-5,10,15,20-tetraphenylporphyrin (2) was prepared in 85% yield from zinc(II) 2-hydroxymethyl-5,10,15,20-tetraphenylporphyrin after the reaction with NaN3

• and BF3·Et2O in 1,4-dioxane at 80 °C for 2 hours [51]. Initially, the copper(II) and zinc(II) derivatives of β-triazoloporphyrin–xanthone conjugates 6a,d,g and 7a,c were synthesized in 60–76% yields through a copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between copper(II) 2-azido

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• carbonates. In consequence, industrially relevant catalysts, combined with efficient processes, have only recently emerged for the manufacture of alternating polycarbonates [10] and polyethercarbonates [11]. The respective research has mainly focussed on homogeneous zinc–alkoxide complexes [12] and chromium

• explored in several studies. Rieger et al. studied the mechanisms of the copolymerisation by homogeneous chromium(III)– and aluminium(III)–salen complexes and by heterogeneous zinc-dicarboxylates [30][31]. Experimental work on the chromium(III)– and aluminium(III)–salen complexes was combined with a

• cyclohexene oxide was the subject of a molecular orbital study on the tri-coordinated di-iminate zinc–alkoxide complex [(BDI)ZnOCH3], whereby BDI is N-(2,6-iPr2C6H3C(Me)-CHC(Me)-N-(2,6-iPr2C6H3) (see Figure 1) [33]. The study was based on the ONIOM [34][35] method, which is a computationally intricate method

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• key intermediate 83 at pilot-scale, a flow-based asymmetric hydrogenation was chosen as an economically more viable option compared to establishing a high-pressure batch process. As depicted in Scheme 14, solutions of the substrate 84 and a zinc triflate additive were combined with the rhodium

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• kinetics. Keywords: azobenzene chemistry; enzyme inhibitors; human carbonic anhydrase II; sulfonamide; X-ray crystallography; Introduction Carbonic anhydrase (CA) is an ubiquitously found zinc-containing metalloenzyme with many isoforms, which all catalyze the conversion of carbon dioxide and water to

• ). Apart from primary binding interactions between the sulfonamide to the zinc center and T199, both of which are well-described [1] (Figure 3b and c), we were looking for secondary interactions resulting from the azobenzene (Figure 3c). Indeed, we found that the methyl group of L198 interacts with the

• of these findings into account, we conclude that the sulfonamide–zinc interaction dominates the binding affinity. The electronic differences of our azobenzene library is expressed by their absorption spectra (as an indicator for the electron richness of the azobenzene) or in their Hammett constants

Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• method to construct the imide functionality is to react the corresponding primary amines with cyclic anhydrides to form amic acids, which are then cyclized using acetic anhydride and sodium acetate in a separate step [26]. Hexamethyldisilazane–zinc chloride has also become one of the most widely used

Chiroptical properties of 1,3-diphenylallene-anchored tetrathiafulvalene and its polymer synthesis

• Masashi Hasegawa,
• Junta Endo,
• Seiya Iwata,
• Toshiaki Shimasaki and
• Yasuhiro Mazaki

Beilstein J. Org. Chem. 2015, 11, 972–979, doi:10.3762/bjoc.11.109

• (9) with a TTF-zinc intermediate (Scheme 1). Previously, 1,3-bis(2-bromophenyl)allene derivatives were reported by Ready et al. as a precursor of an asymmetric catalyst [18]. To obtain the chiral 1,3-bis(4-bromophenyl)allene (8) in a larger scale, we modified the synthesis and the chiral separation

Carboxylated dithiafulvenes and tetrathiafulvalene vinylogues: synthesis, electronic properties, and complexation with zinc ions

• Yunfei Wang and
• Yuming Zhao

Beilstein J. Org. Chem. 2015, 11, 957–965, doi:10.3762/bjoc.11.107

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• regulate G-proteins involved in filopodia, lamellipodia, and contraction [7]. Moreover, FAK can directly serve to gene regulation. It can transfer from focal adhesions to the nucleus to target ubiquitination of the cell-cycle mediator p53 and act as a transcription co-regulator with the GATA4 zinc-finger

Discrete multiporphyrin pseudorotaxane assemblies from di- and tetravalent porphyrin building blocks

• Mirko Lohse,
• Larissa K. S. von Krbek,
• Sebastian Radunz,
• Suresh Moorthy,
• Christoph A. Schalley and
• Stefan Hecht

Beilstein J. Org. Chem. 2015, 11, 748–762, doi:10.3762/bjoc.11.85

• convergent by first preparing two different (zinc)porphyrin cores 1 and 2 (Scheme 1), which are equipped with two and four bromine atoms in the m-position of the meso-phenyl substituents, respectively, for further functionalization. Zinc porphyrins 1 and 2 have been synthesized following standard protocols

• for symmetrical [76] A4 and trans-disubstituted [77] A2B2 meso-functionalized porphyrins. The tetrabrominated core 1 was synthesized from aldehyde 3 and pyrrole (4) to form the free base porphyrin 5, which is subsequently converted into its zinc complex 1. On the other hand the difunctional core 2 was

• obtained through the condensation of aldehyde 3 with mesityldipyrromethane (6) followed by metalation of the intermediately formed free base porphyrin 7 to give its respective zinc complex 2. In the next step, axle precursor 8 was synthesized by reductive amination of 4-bromobenzaldehyde (9) and

Self-assembly of heteroleptic dinuclear metallosupramolecular kites from multivalent ligands via social self-sorting

• Christian Benkhäuser and
• Arne Lützen

Beilstein J. Org. Chem. 2015, 11, 693–700, doi:10.3762/bjoc.11.79

• (trimethylsilyl)acetylene into 7 in a yield of 85% [27]. Alkyne 7 was then subjected to a Negishi reaction with 2-bromopyridine (8) derived zinc organyl 9 to give the silyl-protected ethynylated bipyridine 10 in excellent yield of 99% which was subsequently desilylated under standard conditions to give terminal