The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• via C–H bond insertion by carbenes and nitrenes. Applications to natural product synthesis, a description of the essential elements in substrate-controlled reactions, and mechanistic details of transformations are presented. Overall, these transformations allow the construction of important ring

• systems rapidly and efficiently, though additional catalyst development is needed. Keywords: bridged rings; carbene; cascade reaction; C–H bond insertion; nitrene; Introduction Bridged polycyclic natural products are an inviting challenge to the synthetic chemist for their rich display of functional

• access to multiple targets from a single intermediate produced on large scale that may be stored until needed [17]. The C–H bond insertion has great potential as a method to access different polycyclic isomers (e.g., 1 or 3) through C–C or C–N bond formation from a carbene or nitrene, respectively

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

• J. V. Santiago A. H. L. Machado Grupo de Tecnologia em Síntese Orgânica, Instituto de Química, Universidade de Brasília, Campus Universitário Darcy Ribeiro, 4478, CEP 70904-970, Asa Norte, Brasília-DF, Brasil 10.3762/bjoc.12.87 Abstract The enantioselective carbenoid insertion into C(sp3)–H bonds

• enantioselective insertion of these organometallic species into these non-polarized bonds is a recent topic in the chemical literature, when compared to the first reports of carbenoid chemistry around the 1950s. Carbene is a molecule bearing a functional group with a divalent neutral carbon. This structural

• carbene carbon atom, the insertion reaction can be more or less selective. Very electrophilic carbenoid intermediates, for example, display little regio- and stereoselectivity, favoring the occurrence of side reactions. A less electrophilic carbenoid intermediate, on the other hand, has a lower reactivity

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

• development of intermolecular C–H insertion in the application of C(sp3)–H bond functionalizations, especially for light alkanes, is reviewed. The challenging problem of regioselectivity in C–H bond insertions has been tackled by the use of sterically bulky metal catalysts, such as metal porphyrins and silver

• (I) complexes. In some cases, high regioselectivity and enantioselectivity have been achieved in the C–H bond insertion of small alkanes. This review highlights the most recent accomplishments in this field. Keywords: alkane; diazo compounds; C–H bond functionalization; C–H bond insertion; metal

• simple aliphatic C(sp3)–H bonds. In this context, catalytic metal–carbene C(sp3)–H bond insertion represents an alternative and unique approach for this purpose. Metal–carbene insertion into a C(sp3)–H bond, well-recognized as one of the typical reactions of carbene species, have been studied extensively

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• -Boc-α-N-Cbz-L-ornithine (20) was transformed into sulfamate 21. Subsequently, the C–H insertion representing the key step of this synthesis was examined with two different catalysts and different reaction conditions. Despite different ratios in the outcome of the C–H insertion in favour of the

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• . It has been achieved in the past for example by Francis and co-workers and Ball and co-workers using rhodium-catalyzed carbene-insertion reactions [21][22][23] or via direct C–H arylation [24][25][26][27][28][29]. If the installation of alkynes on peptides or proteins is desired, an indirect method

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• starting materials. The reaction proceeds with excellent regio- and diastereoselectivity which is presumably due to a regio- and stereoselective alkene insertion into the strained metalla-aziridine intermediate 84. Photoredox catalysis Visible-light photoredox catalysis has emerged as a powerful platform

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

• . Thus, treatment of the shown octa-bromide (Scheme 6) with resorcinol led to the insertion of a third row of aromatic rings and the corresponding deep-cavity cavitand [17][18]. This “weaving process” can be carried out with many resorcinol derivatives, but the necessity of using variations on the

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• . Thereby the ketosynthases neighbored by genes related to fatty acid synthesis had not been considered. Insertion mutants were generated and the influence on photopyrone production was analyzed. Thus, the gene ppyS (for photopyrone synthase) was identified, since all other disruption mutants did not yield

Interactions between 4-thiothymidine and water-soluble cyclodextrins: Evidence for supramolecular structures in aqueous solutions

• Vito Rizzi,
• Sergio Matera,
• Paola Semeraro,
• Paola Fini and
• Pinalysa Cosma

Beilstein J. Org. Chem. 2016, 12, 549–563, doi:10.3762/bjoc.12.54

• details about the nature of interactions between S4TdR and all examined CDs. 1H NMR measurements As described in [51], the insertion of a guest molecule into the hydrophobic cavity of the CDs results in the shift of guest and/or host molecular signals in 1H NMR spectra. More specifically, if a guest

• greater than 1. Rekharsky et al. [60] discuss these variations, namely ΔδH5 and ΔδH3, and their relative ratios, ΔδH5/ΔδH3, considering the ratio as an indication of the stability of the complex. If the ratio ΔδH5/ΔδH3 is below 1, the insertion of the aromatic ring of the guest into the host cavity

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

• insertion. The trend seen with electron-donating substituents on the aryl iodide was not seen with the electron-withdrawing substituent, NO2; p-iodonitrobenzene did not give the highest yield for the ring-opened product (73%, Table 2, entry 7). Instead, the highest yield was seen with m-iodonitrobenzene (88

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• better the so-called nearest-neighbor exclusion principle (NEP), wherein intercalators at full saturation of a DNA helix bind every other site (i.e., one intercalator per two base-pairs) [6]. Figure 2a schematically shows how insertion of monointercalators at full saturation leads to a DNA helix with

Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

• Miriana Kfoury,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2016, 12, 29–42, doi:10.3762/bjoc.12.5

• CD. Moreover, the clear upfield shift of the H-6 proton of CD could be explained by the deep insertion of guests and showed that interactions occurred between 1 and 2 protons and the narrow side of CD due to steric hindrance. Particularly, the shift of H-3, H-5 and H-6 to higher magnetic fields could

Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports

• Krzysztof Skowerski,
• Jacek Białecki,
• Stefan J. Czarnocki,
• Karolina Żukowska and
• Karol Grela

Beilstein J. Org. Chem. 2016, 12, 5–15, doi:10.3762/bjoc.12.2

• still of interest. It brings some additional possibilities to be explored, such as on-demand catalyst removal and insertion controlled by a magnetic field. If it is required, complex 8 can then easily be recovered from the support by simply washing the heterogeneous material 8-Fe with a polar solvent

Recent advances in metathesis-derived polymers containing transition metals in the side chain

• Ileana Dragutan,
• Valerian Dragutan,
• Bogdan C. Simionescu,
• Albert Demonceau and
• Helmut Fischer

Beilstein J. Org. Chem. 2015, 11, 2747–2762, doi:10.3762/bjoc.11.296

• ) polymerization [15][16], living ionic polymerizations, specifically ring-opening polymerization (ROP) [17], as well as migration insertion polymerization (MIP) [18], acyclic diene metathesis polymerization (ADMET) [19][20] and ring-opening metathesis polymerization (ROMP) [21][22][23][24][25][26][27]. These

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• the tricyclic core were controlled via Rh-catalyzed stereoselective C–H insertion and the subsequent reduction from the convex face. Keywords: bifunctional catalysis; hydrogen bonding; organocatalyst; oxa-Michael; prostacyclin; Introduction Prostacyclin (PGI2, Figure 1) is a physiologically active

• ) at the ortho position was methyl, or via coupling reactions with C4 units when X was a bromo substituent. The cis-fused tricyclic core of 3 was assumed to be constructed by a stereoselective C–H insertion of diazoester 4, which can be readily prepared from the Weinreb amides 5 or 6 via Claisen

• -dimethylimidazolinium hexafluorophosphate (ADMP) [40][41][42] to give the diazoester 14. Rhodium catalysed C–H insertion [43][44] of 14 proceeded smoothly to furnish the tricyclic ketoester, which was found to be unstable to purification on column chromatography, presumably due to decomposition of the ketoester moiety

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

• complexation invariably involves insertion of the D-ring of 2ME from the secondary side of each CD molecule, with the 17-OH group generally hydrogen bonding to a host glycosidic oxygen atom within the CD cavity, while the A-ring and part of the B-ring of 2ME protrude from the secondary side. In the case of the

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• iodide 97. The following palladium-catalyzed B-alkyl Suzuki–Miyaura cross coupling between the borane derived from alkene 98 and vinyl iodide 97 furnished a Z-configured alkene. Deprotection of the trimethylsilyl ether then afforded alcohol 99. A rhodium(II)-catalyzed O–H insertion reaction of the

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

• Josiphos enantiomer used, in both cases with good enantioselectivities (85–92% ee). Subsequent chain elongation followed by a 1,4-ACA reaction was described and enabled the enantioselective insertion of an additional methyl group. With trialkylaluminium reagents Only a few systems are known to perform

• ]. Unsymmetrical bidentate hydroxyalkyl precursor L12 led to the most efficient system in the insertion of methyl groups in such architectures, being highly versatile synthetic platforms [34][35]. A wide variety of α,β-unsaturated acyl-N-methylimidazoles could thus be reacted in high yields and

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• provides a practical approach to complement the above catalytic version on the sulfonamidation of secondary and tertiary alkyl C–H bonds (Scheme 4) [46]. As an early known tactic with broad application, the nitrene insertion was frequently employed in the sulfonamidation of saturated C–H bonds. However

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

• Nicolas Desbois,
• Sandrine Pacquelet,
• Adrien Dubois,
• Clément Michelin and
• Claude P. Gros

Beilstein J. Org. Chem. 2015, 11, 2202–2208, doi:10.3762/bjoc.11.239

• reported the successful synthesis of 64Cu-chelated porphyrin photosensitizers and a tumor targeting peptide. To the best of our knowledge, no previous example of the preparation of radioligand 64Cu corrole has been so far reported. Due to their easy copper insertion [21], corroles can be considered as

• trifluoroacetic acid, followed by oxidation under the action of DDQ. Cu and Ga complexes were prepared by the strategy outlined in Scheme 2. The insertion of Cu into corrole 1 was easily achieved with Cu(OAc)2·H2O in THF during 15 min. To obtain the gallium corrole 8b, free-base azidocorrole 1 was dissolved in a

• the synthesis of copper porphyrin 9a, compound 2 [10] was reacted with Cu(OAc)2. The gallium complex of porphyrin 2 was prepared starting from GaCl3 in refluxing AcOH. The insertion of indium into porphyrin 2 was achieved by heating with InCl3 salt in AcOH. Finally, manganese chloride and 2 were

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• with the Corey reagent. The taste evaluation of these bisabolanes has demonstrated that the insertion of a hydroxy group on the side chain of hernadulcin annuls its intense sweetness. Hernandulcin and other bisabolanic derivatives extracted from Lippia dulcis. Synthesis of (+)-neoisopulegol. Reagents

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• corresponding tri- and tetrasubstituted pyridines 9 (Scheme 2C). This use of α,β-unsaturated oxime reagents for the synthesis of pyridines is unique from transition metal-catalyzed C–H bond functionalization processes that require a regioselective migratory insertion. This route is appealing due to the

• substituents and regiospecificity of the transformation due to the use of the Chan–Lam reaction for the synthesis of the nitrone precursor are noteworthy and provide advantages over pyridine syntheses that require regioselective insertion reactions or nucleophilic additions. To better understand the conversion

Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• many of the reactions between indoles and metal-bound carbenes are unclear [5][6][7][8]. We have for some time worked with halodiazoacetates and studied their reactivity in cyclopropanation reactions [17], C–H insertion and Si–H insertion reactions [18]. Halodiazoacetates can be made quantiatively and

• Scheme 5. We found no trace of a cyclopropanation-ring expansion product in the crude reaction mixture, but isolated ethyl 2,2-bis(1-methyl-1H-indol-3-yl)acetate in 69% yield. A possible explanation for the formation of the bisindol acetate can be rationalized by assuming a C–H insertion of the Rh

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• with the aid of a carbene insertion reaction. Further, this cyclopropene system 16 was subjected to RRM in the presence of catalyst 1 to generate 3-pyrroline derivatives 18a,b using simple starting materials in a single step (Scheme 1). A wide range of heterocycles have been assembled by RRM. When a

A comprehensive study of olefin metathesis catalyzed by Ru-based catalysts

• Albert Poater and
• Luigi Cavallo

Beilstein J. Org. Chem. 2015, 11, 1767–1780, doi:10.3762/bjoc.11.192

• , Thuwal 23955-6900, Saudi Arabia 10.3762/bjoc.11.192 Abstract During a Ru-catalyzed reaction of an olefin with an alkylidene moiety that leads to a metallacycle intermediate, the cis insertion of the olefin can occur from two different directions, namely side and bottom with respect to the phosphine or N

• ][28][29], towards the associative or the concerted mechanisms [30]. The next metallacycle intermediate is due to the reaction of the olefin with the alkylidene moiety. Nevertheless in the cis insertion of the olefin, this olefin can enter from two different directions, side and bottom, displayed in

• Scheme 2. Regarding this cis insertion of the olefin, even though most papers favor the side insertion of the olefin (see Scheme 2) over the bottom insertion [31], both pathways might exist depending on the ligands and type of olefin. Since the year 2000 many papers try to unravel the preference for the