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The sponge derived 2,5-diketopiperazine metabolite barettin is a potent antifouling compound effective against the settlement and metamorphosis of barnacles. Simplified derivatives of barettin have previously been shown to display similar inhibitory properties. The synthetic derivative benzo[g]dipodazine has been reported to display significantly improved antifouling properties in comparison with the native barettin with inhibitory activities as low a 0.034 µM reported against barnacle cyprid settlement. In the current study we report the antifouling activity of 29 synthetic analogs designed and inspired by the potent antifouling effect seen for benzo[g]dipodazine. The library contains mainly not only dipodazine derivatives but also disubstituted diketopiperazines and compounds incorporating alternative heterocyclic cores such as hydantoin, creatinine, and rhodanine. Several of the prepared compounds inhibit the settlement of Amphibalanus improvisus cyprids at low micromolar concentrations, in parity with the natural barettin. While several highly active compounds were prepared by incorporating the benzo[g]indole as hydrophobic substituent, the remarkable antifouling effect reported for benzo[g]dipodazine was not observed when evaluated in our study.

The management of neurological disorders such as dementia associated with Alzheimer’s or Parkinson’s disease includes the use of cholinesterase inhibitors. These compounds can slow down the progression of these diseases and can also be used in the treatment of glaucoma and myasthenia gravis. The majority of the cholinesterase inhibitors used in the clinic are derived from natural products and our current paper describes the use of a small marine pharmacophore to develop potent and selective cholinesterase inhibi- tors. Fourteen small inhibitors were designed based on recent discoveries about the inhibitory potential of a range of related marine secondary metabolites. The compounds were evaluated, in kinetic enzymatic assays, for their ability to inhibit three different cholinesterase enzymes and it was shown that compounds with a high inhibitory activity towards electric eel and human recombinant acetylcholinesterase (IC50 between 20–70 μM) could be prepared. It was also shown that this compound class was particularly active against horse serum butyrylcholinesterase, with IC50 values between 0.8–16 μM, which is an order of magnitude more potent than the clinically used positive control neostigmine. The compounds were further tested for off-target toxicity against both human umbilical vein endothelial cells and bovine and human erythrocytes and were shown to display a low mammalian cellular toxicity. Overall, the study illus- trates how the brominated dipeptide marine pharmacophore can be used as a versatile natural scaffold for the design of potent, and selective cholinesterase inhibitors.

Halogen bonding is a flourishing field of research, but has for long been little recognized. The same goes for its scientific hero, Odd Hassel, who laid the foundations for all current developments. The crystallographic observation of halogen−oxygen interatomic distances shorter than the sum of the van der Waals radii of the involved atoms, and the interpretation of this phenomenon as a charge-transfer interaction, have been ground-breaking. Today, charge-transfer to a polarized halogen is not any longer seen as “odd”, but is commonly referred to as halogen bonding, and is widely exploited in chemistry. Despite the recognition of Hassel's work with a Nobel prize in 1969, surprisingly little appreciation is given to date to the devoted scientist, who established a world-leading laboratory during one of the darkest eras of history. Herein, we wish to revive the legacy and highlight the impact of Odd Hassel's ground-breaking discoveries.

Herein, we describe a rapid microwave-assisted, metal-free synthesis of substituted quinoxalinones and quinoxalines using the carbene-mediated reaction between aryldiazo esters and 1,2-diamines. The reaction can encompass a range of substituents and structural variations to afford quinoxalin-2-ones in 14–80 % yield and corresponding quinoxalines in good to excellent yields upon oxidation (67–96 %). The approach can be employed to generate symmetrical and unsymmetrical 2,3-diarylquinoxalines, bis-quinoxalines as well as novel quinoxaline-substituted diazo esters and should be a valuable addition to the heterocycle synthesis toolbox.

The phytoplanktonic composition with a focus on cyanobacteria, intra- and extracellular microcystins (MCs) concentrations and MCs concentrations in fish tissues were investigated in Lake Hora-Arsed...

Herein is reported a substantially improved synthesis of 2-substituted benzimidazoles by condensation of 1,2-diaminoarenes and aldehydes using methanol as the reaction medium. The developed method afforded moderate to excellent yields (33–96%) at ambient temperature, displays high functional group tolerance, is conducted open to air, and requires only one minute reaction time under catalyst- and additive-free conditions. Moreover, the efficient protocol permits scale-up to multi-gram scale synthesis of benzimidazoles and will become a method of choice when constructing such heterocyclic systems.

Accepted manuscript version, licensed CC BY-NC-ND 4.0. This study was carried out with a view of understanding the temporal dynamics of microcystin concentrations in both algal seston and water samples and the associated public health risk. All the major MC variants, namely MC-LR, MC-YR, and MC-RR, were detected in both the algal seston and water samples. In the majority of the samples, the most potent variant, MC-LR, constituted the greatest proportion of the total MC concentration suggesting extremely high potential public health risk. The exceptionally high concentrations (μg L−1) of all the variants, MC-LR (815), MC-YR (466.6) and MC-RR (265.68), were observed in May. Although the extracellular MCs were relatively less concentrated and less frequently detected, concentrations (μg L−1) of up to 20 of MC-LR, 6.13 of MC-YR, and 1.27 MC-RR were encountered. The strong and significant association between Microcystis abundance and concentration of nitrate (Spearman Rank Order Correlation r = 0.793, p Microcystis, and may have consequently influenced the MC levels in the reservoir.

The synthesis of novel 5,7-diaryl and diheteroaryl indoles has been explored

The synthesis of novel 5,7-diaryl and diheteroaryl indoles has been explored via efficient double Suzuki–Miyaura coupling. The method notably employs a low catalyst loading of Pd(PPh3)4 (1.5 mol%/coupling) and water as the reaction solvent to obtain 5,7-diarylated indoles without using N-protecting groups in up to 91% yield. The approach is also suitable for N-protected and 3-substituted indoles and constitutes an important green and convenient arylation strategy for the benzenoid ring of indoles. The synthesized diarylindoles are fluorescent.

Source at https://doi.org/10.1186/s13104-018-3924-2. Licensed CC BY-NC-ND 4.0. Objectives: In vivo evaluations of a gonadotropin releasing hormone-receptor single photon emission computed tomography radiotracer for non-invasive detection of gonadotropin releasing homone-receptors in brain. Results: We have used a simple, robust and high-yielding procedure to radiolabel an alpha-halogenated bioactive compound with high radiochemical yield. Literature findings showed similar alpha-halogenated compounds suitable for in vivo evaluations. The compound was found to possess nano molar affinity for the gonadotropin releasing hormone-receptor in a competition dependent inhibition study. Furthermore, liquid chromatography-mass spectrometry analysis in saline, human and rat serum resulted in 46%, 52% and 44% stability after incubation for 1 h respectively. In addition, rat brain single photon emission computed tomography and biodistribution studies gave further insight into the nature of the compound as a radiotracer.

Herein, we report the presence and concentrations of three most common variants of microcystin (MC–LR, –RR and –YR) in the liver and muscle tissues of wild Nile Tilapia (Oreochromis niloticus), Common Carp (Cyprinus carpio) and African Sharp Tooth Catfish (Clarias gariepinus), which were collected from two study sites of the present study on Koka reservoir, Ethiopia. A total of 36 fish liver and 36 fish muscle samples were collected for six months. Microcystins (MCs) were quantified using LC-ESI-HRMS. The results show that MCs were found in most of the fish liver samples, while they were below the detection limit of the method of analysis used in the muscle samples. In addition to the three most common congeners of MCs, eight other microcystin variants and cylindrospermopsin were detected in the fish liver samples although further detailed study is needed. Among the three most common MC congeners, MC-LR was more prevalent than MC-RR and MC-YR in the liver samples of the three fish species. The highest MC concentration was found in Nile Tilapia collected in April (591.60 μg/g DW of MC-LR), whereas the lowest detected concentration was in Catfish collected in March (2.23 μg/g DW of MC-RR). The results of this study suggest that further intensive assessment and monitoring of the reservoir from different perspectives should be conducted in order to reduce the concentrations of the MCs and seek solutions to the potential public health risk. Moreover, this is the first study ever to report detailed quantification of MCs in fish liver and muscle samples collected from Ethiopia.

A highly efficient and catalyst-free protocol is reported for the synthesis of quinoxalines via the classical cyclocondensation reaction between aryldiamines and dicarbonyl compounds. Remarkably simple and green reaction conditions employing methanol as solvent afforded medium to excellent yield of quinoxalines after only one-minute reaction time at ambient temperature. The conditions allow at least 10 gram scale synthesis of quinoxalines and should be a preferred starting point for optimization and method of choice for applications in the synthetic community.

Stationary and slow-moving marine organisms regularly employ a natural product chemical defense to prevent being colonized by marine micro- and macroorganisms. While these natural antifoulants can be structurally diverse, they often display highly conserved chemistries and physicochemical properties, suggesting a natural marine antifouling pharmacophore. In our current report, we investigate the marine natural product phidianidine A, which displays several chemical properties found in highly potent marine antifoulants. Phidianidine A and synthetic analogues were screened against the settlement and metamorphosis of Amphibalanus improvisus cyprids, and several of the compounds displayed inhibitory activities at low micromolar concentrations with IC50 values down to 0.7 μg/mL observed. The settlement study highlights that phidianidine A is a potent natural antifoulant and that the scaffold can be tuned to generate simpler and improved synthetic analogues. The bioactivity is closely linked to the size of the compound and to its basicity. The study also illustrates that active analogues can be prepared in the absence of the natural constrained 1,2,4-oxadiazole ring. A synthetic lead analogue of phidianidine A was incorporated in a coating and included in antifouling field trials, where it was shown that the coating induced potent inhibition of marine bacteria and microalgae settlement.

We report the synthesis, radiosynthesis and biological characterisation of two gonadotropin‐releasing hormone receptor (GnRH−R) antagonists with nanomolar binding affinity. A small library of GnRH−R antagonists was synthesised in 20–67 % overall yield with the aim of identifying a high‐affinity antagonist capable of crossing the blood–brain barrier. Binding affinity to rat GnRH−R was determined by autoradiography in competitive‐binding studies against [125I]buserelin, and inhibition constants were calculated by using the Cheng–Prusoff equation. The radioligands were obtained in 46–79 % radiochemical yield and >95 % purity and with a molar activity of 19–38 MBq/nmol by direct nucleophilic radiofluorination. Positron emission tomography imaging in rat under baseline conditions in comparison to pretreatment with a receptor‐saturating dose of GnRH antagonist revealed saturable uptake (0.1 %ID/mL) into the brain., Hot‐flashes light the path to hormone receptor functions in brain: Two novel GnRH PET radioligands have been developed and tested in rat brain tissue. For the first time, a ligand, [18F]4, shows concentration‐dependent, saturable binding combined with saturable uptake into the brain. On this basis, the development of PET radiotracers for GnRH imaging in the brain becomes feasible.

A mild, green and highly efficient protocol was developed for the synthesis of substituted phenols via ipso-hydroxylation of arylboronic acids in ethanol. The method utilizes the combination of aqueous hydrogen peroxide as the oxidant and H2O2/HBr as the reagent under unprecedentedly simple and convenient conditions. A wide range of arylboronic acids were smoothly transformed into substituted phenols in very good to excellent yields without chromatographic purification. The reaction is scalable up to at least 5 grams at room temperature with one-minute reaction time and can be combined in a one-pot sequence with bromination and Pd-catalyzed cross-coupling to generate more diverse, highly substituted phenols.

The increased expression of gonadotropin releasing hormone receptor (GnRH‐R) in brain has been strongly linked to Alzheimer disease. Therefore, the development of radiolabeled imaging agents for GnRH‐R is relevant for early diagnosis of Alzheimer disease. We have recently disclosed the discovery of two promising compounds displaying nanomolar‐range affinity for the GnRH‐R. In the present study, a preclinical evaluation of the compound properties was performed to evaluate their potential as single photon emission computed tomography (SPECT) radiotracers for imaging the GnRH‐receptor. The compounds were assessed in vitro by performing serum stability analysis by human and rat serum, metabolic profiling by human liver microsomes, and exploratory rat brain autoradiography. The investigated compounds displayed satisfactory stability against human, rat serum, and liver microsomal metabolism, which favors their potential as SPECT‐imaging agents. Additionally, we identified and quantified the formation rate of the metabolites by fragmentation of up to five mass spectrometric stages. The GnRH‐R rat brain specificity of these compounds was tested in competition with a known ligand for the receptor and the in vitro autoradiography confirmed that compounds 3 and 4 binds to rat GnRH‐R in different rat brain regions.

The copper-mediated azide-alkyne cycloaddition has been studied to achieve late-stage introduction of iodine onto novel triazole-benzimidazole Gonadotropin Releasing Hormone (GnRH)-receptor antagonists. Moreover, the reaction conditions can affect a direct regioselective C–H iodination of the benzimidazole, leading to a range of novel iodo-analogues. The methodologies are powerful strategies for late-stage 123I-labelling of complex bioactives. Our investigations have generated two highly promising 123I-labelled radiotracer candidates that retain high affinities for the GnRH-receptor.

Source at https://doi.org/10.5772/intechopen.87068. This chapter describes contemporary strategies for selective catalytic intermolecular functionalization of the benzimidazole scaffold. Functionalization at nitrogen and position C-2 is well developed employing copper, palladium, rhodium, nickel, and cobalt catalysis. Direct CH activation is the predominant approach to C-2 functionalization. Nickel-based catalysts can activate C—O bonds in conjunction with C—H activation at benzimidazole which grants access to a very broad range of phenols and enols as convenient functionalization precursors in this chemistry. The remaining carbon positions of benzimidazoles are typically functionalized via a sequential halogenation/coupling strategy to ensure selectivity. A key success factor in enabling these chemistries has been the fine-tuning of catalyst-ligand combinations.

Accepted manuscript version. Published version available at https://doi.org/10.1016/j.bioorg.2018.11.024. Licensed CC BY-NC-ND 4.0. The marine environment remains a rich source for the discovery and development of novel bioactive compounds. The present paper describes the design, synthesis and biological evaluation of a library of small molecule heterocyclic mimetics of the marine 2,5-diketopiperazine barettin which is a powerful natural antioxidant. By mainly focusing on the influence from the brominated indole and heterocyclic core of barettin, a library of 19 compounds was prepared. The compounds comprised a heterocyclic core, either a 2,5 diketopiperazine, an imidazolidinedione or a thioxothiazolidinone, which were mainly monosubstituted with ranging bulky substituents. The prepared compounds were screened for activity in a cellular lipid peroxidation assay using HepG2 cells. Several of the synthetic compounds showed antioxidant properties superior to the positive control barettin. Two of the prepared compounds displayed inhibitory activity similar to commercial antioxidants with significant inhibition at low µg/mL concentrations. The toxicity of the compounds was also investigated against MRC-5 lung fibroblasts and none of the included compounds displayed any toxicity at 50 µg/mL.

Magnetic nanoparticles display a range of unique properties of interest to fields such as water treatment, drug delivery, catalysis, and many more. Widespread use of magnetic nanoparticles relies heavily on one's ability to separate them effectively from other media, for example in water treatment. In this work, an efficient method to separate magnetic nanoparticles from organic solvent using magnetic ionic liquids is demonstrated for the first time. Fourier transform infrared spectroscopy, ultraviolet–visible spectroscopy, and microscopy were employed to investigate the authors’ model system. This work will greatly impact future directions in the science of separating nanoparticles and applications of ionic liquids.

In this Frontiers article, we highlight how state-of-the-art density functional theory calculations can contribute to the field of homogeneous photoredox catalysis. We discuss challenges in the fields and potential solutions to be found at the interface between theory and experiment. The exciting opportunities and insights that can arise through such an interdisciplinary approach are highlighted.

A summary of recent synthetic approaches to 3,4-dihydroquinoxalin-2-ones is discussed herein along with highlights of biological activity. The synthetic approaches include access to enantiopure 3,4-dihydroquinoxalin-2-ones from chiral pool amino acids via coupling/cyclization, Michael addition/cyclization cascades, 3,3-disubstituted systems from multicomponent couplings, Bargellini reaction, or photochemical reduction.

This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Journal of Physical Chemistry A, copyright © American Chemical Society after peer review. To access the final edited and published work see http://doi.org/10.1021/acs.jpca.7b10595 The host-guest chemistry of cryptophanes is an active research area because of its applications in sensor design, targeting small molecules and atoms in environmental and medical sciences. As such, the computational prediction of binding energies and nuclear magnetic resonance (NMR) properties of different cryptophane complexes are of interest to both theoreticians and experimentalists working in host-guest based sensor development. Herein we present a study of 10 known and some newly proposed cryptophanes using density functional theory (DFT) calculations. We benchmark the description of non-bonding interactions by different DFT functionals against spin-component-scaled, second-order Møller–Plesset theory (SCS-MP2) and predict novel host molecules with enhanced affinity towards methane and Xenon - two representative systems of high interest. We demonstrate the power and limitations of the different computational methods in describing the binding and NMR-properties of these established and novel host systems. The results show the importance of including dispersion corrections in the DFT functionals. The overall analysis of the dispersion corrections indicated that results obtained from pure DFT functionalsshould be used cautiously when drawing conclusions for molecular systems with considerable weak interactions. Proposed analogues of cryptophane-A, where the alkoxy bridges are replaced by alkyl chains, are predicted to display enhanced affinity towards both methane and Xenon.

Both pathogenic bacteria and fungi are developing resistance to common antimicrobial treatment at an alarming rate. To counteract this development, it is of essence to develop new classes of antimi ...

Visible-light photoredox catalysis has come forth as a powerful activation mode in chemical synthesis, affording the development of a multitude of new strategies for molecular construction. However, detailed mechanistic knowledge of the various subprocesses involved is lacking, and new tools for addressing this are needed to drive innovation forward in the area. Herein, we describe predictions of ground- and excited-state redox potentials of ruthenium and iridium photocatalysts using nonrelativistic and scalar relativistic zero-order regular approximation density functional theory (DFT) methods. The computed redox potentials were correlated with experimental values and found to reproduce them well. Relativistic corrections were found to be important to reproduce experimental data. Moreover, the computational protocol allows us to estimate redox potentials that are not currently available in the literature or are difficult to determine experimentally. The mechanistic details of the photocatalyzed C–H funct...

In this communication, we report the synthesis and characterization of a library of small molecule antagonists of the human gonadotropin releasing hormone receptor based upon the 2-(4-tert-butylphenyl)-4-piperazinyl-benzimidazole scaffold via Cu-catalysed azide alkyne cycloaddition. Our main purpose was to find a more soluble compound based on the WAY207024 lead with nanomolar potency to inhibit the GnRH receptor. A late stage diversification by the use of click chemistry was, furthermore developed to allow for expansion of the library in future optimisations. All compounds were tested in a functional assay to determine the individual potency of inhibiting stimulation of the receptor by the endogenous agonist GnRH. In conclusion, we found that compound 8a showed improved solubility compared to WAY207024 and nanomolar affinity to GnRH receptor.

Published version. source at http://dx.doi.org/10.1055/s-0036-1588719 Herein is disclosed a novel visible-light photocatalytic double C–H functionalization of indoles. The reaction affords 2,3-difunctional- ized indoles in up to 84% yield, but the reaction rate depends strongly on electronic substituent effects. Mechanistic DFT studies and control experiments suggest that the secondary functionalization occurs through an independent photocatalytic oxidation of bromide ions formed during the reaction to generate molecular bromine capable of electrophilic C-3 bromination.

A nanophotonic sensor for sensitive detection of methane in water solution is presented. Cryptophane-A doped waveguide cladding provides for methane pre-concentration on a chip, resulting in a detection limit of 60 ppm (86 nM).

Visible-light photocatalyzed (VLPC) late-stage C-H functionalization is a powerful addition to the chemical synthesis toolkit. VLPC has a demonstrated potential for discovery of elusive and valuable transformations, particularly in functionalization of bioactive heterocycles. In order to fully harvest the potential of VLPC in the context of complex molecule synthesis, a thorough understanding of the elementary processes involved is crucial. This would enable more rational design of suitable reagents and catalysts, as well as prediction of activated C-H sites for functionalization. Such knowledge is essential when VLPC is to be employed in retrosynthetic analysis of complex molecules. Herein, we present a density functional theory (DFT) study of mechanistic details in the C-H functionalization of bioactive heterocycles exemplified by the methylation of the antifungal agent voriconazole. Moreover, we show that readily computed atomic charges can predict major site-selectivity in good agreement with experimental studies and thus be informative tools for the identification of active C-H functionalization sites in synthetic planning.

We report 50-fold sensitivity enhancement of our integrated methane sensors when incorporating cryptophane-A in the waveguide cladding. A detection limit of 6 ppm was demonstrated with only 3 cm sensing length.

Synthetically useful transformations arise from the thermal decomposition of aryldiazoacetates in the presence of primary and secondary amines without the use of a metal catalyst. Thermally generated, free donor/acceptor carbenes directly undergo N-H insertion with amines through selective aza-ylide formation to afford a variety of α-amino esters in 53-96% yields.

We report a methane sensor based on an integrated Mach-Zehnder interferometer, which is cladded by a styrene-acrylonitrile film incorporating cryptophane-A. Cryptophane-A is a supramolecular compound able to selectively trap methane, and its presence in the cladding leads to a 17-fold sensitivity enhancement. Our approach, based on 3 cm-long low-loss Sisub3/subNsub4/subrib waveguides, results in a detection limit as low as 17 ppm. This is 1-2 orders of magnitude lower than typically achieved with chip-scale low-cost sensors.

Silver(I)-catalyzed reactions of vinyldiazoacetates have been shown to involve the intermediacy of silver-carbenoid species. The silver vinylcarbenoid displays a strong preference for electrophilic reactivity at the vinyl terminus in O–H insertion reactions.

This is the peer reviewed version of the following article: Fjellaksel, R., Dugalic, D., Demissie, T.B., Riss, P., Hjelstuen, O.-K., Sundset, R. & Hansen, J.H. (2018). An Acylation-Finkelstein Approach to Radioiodination of Bioactives: The Role of Amide Group Anchimeric Assistance. Journal of Physical Organic Chemistry. https://doi.org/10.1002/poc.3835, which has been published in final form at https://doi.org/10.1002/poc.3835. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Herein, we report a straightforward sequential acylation‐Finkelstein approach to achieve iodination of amine containing bioactives. The utility was demonstrated by successful radiolabelling with 123I in high radiochemical yield. Moreover, microwave‐assisted Finkelstein reaction can be employed to enhance conversion and reaction rates to obtain the desired iodides. The method is of interest for radioiodination of amine‐containing bioactives. The mechanistic details of the iodination process were studied by kinetics and density functional theory calculations, which revealed the mechanistic complexity of the reaction involving amide group anchimeric assistance. We disclose a number of fundamental aspects of amide group anchimeric assistance in substitution reactions.

The catalytic activity of heterobimetallic Bi-Rh paddlewheel carboxylate complexes has been evaluated for the first time in the context of metal carbenoid chemistry. The Bi-Rh carboxylate complexes were found to effectively catalyze both cyclopropanation reactions and C-H insertions as well as reactions involving ylide intermediates with similar selectivity profiles to analogous dirhodium complexes. The heterometallic complex BiRh(O(2)CCF(3))(3)(O(2)CCH(3)) was found to be approximately 1600 times less reactive than its homometallic analogue Rh(2)(O(2)CCF(3))(3)(O(2)CCH(3)) toward the decomposition of methyl phenyldiazoacetate. The observed difference in reactivity is in good agreement with a computational model system where axial coordination to the second rhodium active site is considered for the dirhodium catalyst.

The mechanism of rhodium-catalyzed cyclopropanation and C-H functionalization reactions with methyl phenyldiazoacetate and methyl diazoacetate has been studied computationally with DFT. In accordance with experimental data, it has been demonstrated that donor/acceptor rhodium carbenoids display potential energy activation barriers consistent with the much higher selectivity in cyclopropanation and C-H insertion chemistry compared to the traditionally used acceptor carbenoids derived from unsubstituted diazo esters. Significantly higher potential energy barriers were found for transformations of donor/acceptor carbenoids than for those of acceptor systems, primarily due to the inherent stability of the former. Analyses of transition state geometries have led to the development of a rational model for the prediction of the stereochemical outcome of intermolecular C-H insertions with donor/acceptor rhodium carbenoids.

Highly electrophilic ruthenium(I) mixed carbonyl carboxylate complexes exhibit catalytic activity in the cyclopropanation of styrene with methyl phenyldiazoacetate. A particular advantage of these catalysts is their propensity to enhance vinylogous reactivity in the reactions of vinyldiazoacetates. The catalytic study was conducted on four known ruthenium(I) mixed carbonyl carboxylate complexes and four new complexes, namely, [Ru2(O2C(2,3,4-F)3C6H2)2(CO)5], [Ru2(O2C(2,4,6-F)3C6H2)2(CO)5], [Ru2(O2CC6F5)2(CO)5], and [Ru2(O2C(3,5-CF3)2C6H3)2(CO)4]. All complexes have been prepared by a combination of solvent-free techniques: melt reactions of ruthenium carbonyl with a benzoic acid followed by gas-phase sublimation−deposition of the products under reduced pressure. X-ray crystallographic characterization revealed a tetranuclear “dimer of dimers” type of structure for the [Ru2(O2CR)2(CO)5] complexes and a polymeric chain for [Ru2(O2C(3,5-CF3)2C6H3)2(CO)4]. Both motifs are built on diruthenium(I,I) units linked...

Reaction of carbenoids with propargylic alcohols results in tandem oxonium ylide formation/[2,3]-sigmatropic rearrangement to yield allenes with high enantioselectivity.

The thermal decomposition of aryldiazoacetates generates carbenes, which directly undergo the C—H insertion reactions with a wide range of primary and secondary alkyl- and aryl/heteroarylamines to give α-arylamino esters in good yields.

Rhodium-catalyzed reactions of tertiary propargylic alcohols with methyl aryl- and styryldiazoacetates result in tandem reactions, consisting of oxonium ylide formation followed by [2,3]-sigmatropic rearrangement. This process competes favorably with the standard O-H insertion reaction of carbenoids. The resulting allenes are produced with high enantioselectivity (88-98% ee) when the reaction is catalyzed by the dirhodium tetraprolinate complex, Rh(2)(S-DOSP)(4). Kinetic resolution is possible when racemic tertiary propargylic alcohols are used as substrates. Under the kinetic resolution conditions, the allenes are formed with good diastereoselectivity and enantioselectivity (up to 6.1:1 dr, 88-93% ee), and the unreacted alcohols are enantioenriched to 65-95% ee. Computational studies reveal that the high asymmetric induction is obtained via an organized transition state involving a two-point attachment: ylide formation between the alcohol oxygen and the carbenoid and hydrogen bonding of the alcohol to a carboxylate ligand. The 2,3-sigmatropic rearrangement proceeds through initial cleavage of the O-H bond to generate an intermediate with close-lying open-shell singlet, triplet, and closed-shell singlet electronic states. This intermediate would have significant diradical character, which is consistent with the observation that the 2,3-sigmatropic rearrangement is favored with donor/acceptor carbenoids and more highly functionalized propargylic alcohols.

The new rhodium catalyst (I) is prepared and highly enantioselective cyclopropanations, tandem cyclopropanation/Cope rearrangements and a combined C—H functionalization/Cope rearrangement are achieved using this catalyst.

Many reactions proceed in higher yields than the previously described rhodium-catalyzed ones, but only electron-rich substituents cause high diastereoselectivities.

Dirhodium tetrakis-(R)-(1-(4-bromophenyl)-2,2-diphenylcyclopropanecarboxylate) (Rh(2)(R-BTPCP)(4)) was found to be an effective chiral catalyst for enantioselective reactions of aryl- and styryldiazoacetates. Highly enantioselective cyclopropanations, tandem cyclopropanation/Cope rearrangements and a combined C-H functionalization/Cope rearrangement were achieved using Rh(2)(R-BTPCP)(4) as catalyst. The advantages of Rh(2)(R-BTPCP)(4) include its ease of synthesis, its tolerance to the size of the ester group in the styryldiazoacetates, and its compatibility with dichloromethane as solvent. Computational studies suggest that the catalyst adopts a D(2)-symmetric arrangement, but when the carbenoid binds to the catalyst, two of the p-bromophenyl groups on the ligands rotate outward to make room for the carbenoid and the approach of the substrate to the carbenoid.

The thermal decomposition of aryldiazoacetates and aryldiazoketones in the absence of a catalyst leads to synthetically useful transformations. The thermal reaction of aryldiazoacetates with alkenes generates cyclopropanes in 68–97% yield and with good diastereoselectivity (up to 19:1 dr) when the aryl substituent is electron-rich. The thermal reaction of aryldiazoketones with alkenes generated cyclobutanones in 71–94% yield and with good diastereocontrol (≥9:1 dr).