Practical and scalable enantioselective synthesis of (+)-majoranolide from Cyrene.

A two-step enantioselective gram scale synthesis of the Persea derived γ-lactones (+)-majoranolide and (+)-majoranolide B has been achieved. The sequence uses the amine promoted crossed condensation of the biorenewable synthon Cyrene with aliphatic aldehydes followed by a Baeyer-Villiger oxidation. Comparison of optical rotation data with the natural products established the absolute configuration of the natural product series, and this work represents the first synthesis of these alkylidene natural products.

Oxa-Michael-initiated cascade reactions of levoglucosenone.

The reactions of aromatic aldehydes and levoglucosenone promoted by methoxide gives bridged α,ß-unsaturated ketones, formed by a series of oxa-Michael-initiated cascade reactions in yields of up to 91% (14 examples). A complex series of equilibria operate during the reaction, and the formation of the bridged species is thermodynamically favored, except in the case of 5-methylfurfural and pyrrole-2-carboxaldehyde. This is the first report detailing this type of aldol/Michael cascade involving oxa-Michael initiation.

Levoglucosenone: Bio-Based Platform for Drug Discovery.

Levoglucosone (LGO) is a bio-privileged molecule that can be produced on scale from waste biomass. This chiral building block has been converted via well-established chemical processes into previously difficult-to-synthesize building blocks such as enantiopure butenolides, dihydropyrans, substituted cyclopropanes, deoxy-sugars and ribonolactones. LGO is an excellent starting material for the synthesis of biologically active compounds, including those which have anti-cancer, anti-microbial or anti-inflammatory activity. This review will cover the conversion of LGO to biologically active compounds as well as provide future research directions related to this platform molecule.

Recent advances in the synthesis of imidazoles.

The review highlights the recent advances (2018-present) in the regiocontrolled synthesis of substituted imidazoles. These heterocycles are key components to functional molecules that are used in a variety of everyday applications. An emphasis has been placed on the bonds constructed during the formation of the imidazole. The utility of these methodologies based around the functional group compatibility of the process and resultant substitution patterns around the ring are described, including discussion of scope and limitations, reaction mechanisms and future challenges.

Cyrene™ is a green alternative to DMSO as a solvent for antibacterial drug discovery against ESKAPE pathogens.

Dimethyl sulfoxide (DMSO) is currently employed across the biomedical field, from cryopreservation to in vitro assays, despite the fact that it has been shown to have an assortment of biologically relevant effects. The amphiphilic nature of DMSO along with its relatively low toxicity at dilute concentrations make it a challenging solvent to replace. A possible alternative is Cyrene™ (dihydrolevoglucosenone), an aprotic dipolar solvent that is derived from waste biomass. In addition to being a green solvent, Cyrene™ has comparable solvation properties and is reported to have low toxicity. Herein the abilities of the two solvents to solubilize drug compounds and to act as non-participatory vehicles in drug discovery for antibacterials are compared. It was demonstrate that the results of standardised antimicrobial susceptibility testing do not differ between drugs prepared from either Cyrene™ or DMSO stock. Moreover, in contrast to DMSO, Cyrene™ does not offer protection from ROS mediated killing of bacteria and may therefore be an improvement over DMSO as a vehicle in antimicrobial drug discovery.

Bio-available Solvent Cyrene: Synthesis, Derivatization, and Applications.

The development of green solvents is one of the key tenets of Green Chemistry as solvents account for the majority of waste stemming from the production of the chemicals on which we have all come to rely. An important class of solvents is the dipolar aprotics, which include N,N-dimethylformamide (DMF) and N-methyl-2-pyrrolidone (NMP). In addition to being derived from non-renewable resources, these solvents are also under increased regulatory pressures that will limit their industrial applications. This Concept concerns the bio-available solvent Cyrene (dihydrolevoglucosenone) as a potential replacement for toxic dipolar aprotic solvents. An emphasis is placed on examining the strengths and weaknesses of Cyrene as a solvent and is accomplished by looking at the synthesis, derivatization, and application in synthetic protocols of Cyrene. With respect to the Twelve Principles of Green Chemistry, this Concept describes a bio-available solvent that should have a disruptive effect on the use of traditional industrial dipolar aprotic solvents.

Charge-transfer dynamics at the dye-semiconductor interface of photocathodes for solar energy applications.

This article describes a comparison between the photophysical properties of two charge-transfer dyes adsorbed onto NiO via two different binding moieties. Transient spectroscopy measurements suggest that the structure of the anchoring group affects both the rate of charge recombination between the dye and NiO surface and the rate of dye regeneration by an iodide/triiodide redox couple. This is consistent with the performance of the dyes in p-type dye sensitised solar cells. A key finding was that the recombination rate differed in the presence of the redox couple. These results have important implications on the study of electron transfer at dye|semiconductor interfaces for solar energy applications.

Resonance Raman Study of New Pyrrole-Anchoring Dyes for NiO-Sensitized Solar Cells.

Three dyes for p-type dye-sensitised solar cells containing a novel doubly anchored pyrrole donor group were synthesised and their solar cell performances were evaluated. Dye 1 was comprised of a phenyl-thiophene linker and a maleonitrile acceptor, which has been established as an effective motif in other push-pull dyes. Two boron dipyrromethane analogues, dyes 2 and 3, were made with different linker groups to compare their effect on the behaviour of these dyes adsorbed onto nickel oxide (dye|NiO) under illumination. The photoexcited states of dye|NiO were probed using resonance Raman spectroscopy and compared to dyes anchored using the conventional 4-aminobenzoic acid moiety (P1 and 4). All three components, the anchor, the linker and the acceptor group were found to alter both the electronic structure following excitation and the overall solar cell performance. The bodipy acceptor gave a better performance than the maleonitrile acceptor when the pyrrole anchor was used, which is the opposite of the triphenylamine push-pull dyes. The linker group was found to have a large influence on the short-circuit current and efficiency of the p-type cells constructed.

Exploring the Reactivity of 2-Trichloromethylbenzoxazoles for Access to Substituted Benzoxazoles.

The reactivity of 2-trichloromethylbenzoxazoles toward various nucleophiles, under metal-free or iron-catalyzed conditions, for the synthesis of substituted benzoxazoles is described. These methods allow for selective substitution at either the 2- or 2'-position of the benzoxazoles using the same starting materials/reagents. This approach allows for the controlled synthesis of a variety of key derivatives from a single 2-trichloromethylbenzoxazole starting material.

Multifaceted catalysis approach to nitrile activation: direct synthesis of halogenated allyl amides from allylic alcohols.

Allyl amides were synthesised from the reaction of allyl alcohols and halogenated nitriles using a platinum multifaceted catalysis approach in which both the nucleophilic addition and subsequent [3,3]-sigmatropic rearrangement steps of the process were catalysed by the same complex. Additionally, (1)H/(13)C{(1)H} NMR and GC studies provided the first insights into the mechanism of this transformation.

Development of a gold-multifaceted catalysis approach to the synthesis of highly substituted pyrroles: mechanistic insights via Huisgen cycloaddition studies.

A novel gold-catalyzed method for the regioselective synthesis of highly substituted pyrroles directly from oximes and alkynes was developed via independent optimization of two key steps of the process. Importantly, a cationic gold(I) species was shown to activate multiple steps along the reaction pathway and therefore act as a multifaceted catalyst. Initial gold-promoted addition of the oxime oxygen to the activated alkyne afforded the O-vinyloxime in situ. The O-vinyloxime was subsequently transformed into the pyrrole via a gold-catalyzed tautomerization, [3,3]-sigmatropic rearrangement, and cyclodehydration process. Notably, this method provides a functional group handle in the form of an ester at the 3/4-position for further exploitation. The proposed mechanistic pathway is supported by a novel application of the Huisgen cycloaddition click reaction, which was used to probe the relative stability of substituted O-vinyloximes. The intermediacy of N-alkenylhydroxylamine O-vinyl ethers and imino ketones or imino aldehydes along the reaction pathway were determined by high-temperature (1)H, (2)H{(1)H}, and (13)C{(1)H} NMR experiments. X-ray crystallographic evidence was used to further support the mechanistic hypothesis.

Decarboxylative Claisen rearrangement reactions: synthesis and reactivity of alkylidene-substituted indolines.

Microwave-assisted decarboxylative Claisen rearrangement (dCr) reactions of substituted acetate derivatives of 3-(hydroxyalkyl)indoles give de-aromatised products. The reactivity of the resultant compounds was evaluated.

Gold-catalysed rearrangement of O-vinyl oximes for the synthesis of highly substituted pyrroles.

O-Vinyl oximes were synthesised from the reaction of oximes with activated alkynes and subsequently rearranged using gold catalysis to afford highly substituted pyrroles in an efficient and regiocontrolled process. Additionally, pyrroles were formed directly from oximes and activated alkynes in a multifaceted catalysis process.

Synthesis of highly substituted pyrroles via nucleophilic catalysis.

A nucleophilic catalysis method providing a concise synthesis of di-, tri-, and tetrasubstituted pyrroles is described. This regioselective one-pot method relies on nucleophilic catalysis of the intermolecular addition of oximes to activated alkynes and thermal rearrangement of the in situ generated O-vinyl oximes to form pyrroles that contain a functional group handle at the C3/C4 position.

Construction of beta-haloenamides via direct copper-promoted coupling of lactams with 2-chloro and 2-bromo vinyliodides.

[reaction: see text] Cu(I)-catalyzed coupling of lactams with (E)-2-chlorovinyliodides or (E)-2-bromovinyliodides produces the corresponding beta-haloenamides in moderate to excellent yields.

meso Substituent effects on the geometric and electronic structures of high-spin and low-spin iron(III) complexes of mono-meso-substituted octaethylporphyrins.

Introduction of a single meso substituent into ClFe(III)(OEP) or K[(NC)(2)Fe(OEP)] results in significant changes in the geometric and/or spectroscopic properties of these complexes. The mono-meso-substituted iron(III) complexes ClFe(III)(meso-Ph-OEP), ClFe(III)(meso-n-Bu-OEP), ClFe(III)(meso-MeO-OEP), ClFe(III)(meso-Cl-OEP), ClFe(III)(meso-NC-OEP), ClFe(III)(meso-HC(O)-OEP), and ClFe(III)(meso-O(2)N-OEP) have been isolated and characterized by their UV/vis and paramagnetically shifted (1)H NMR spectra. The structures of both ClFe(III)(meso-Ph-OEP) and ClFe(III)(meso-NC-OEP) have been determined by X-ray crystallography. Both molecules have five-coordinate structures typical for high-spin (S = 5/2) iron(III) complexes. However, the porphyrins themselves no longer have the domed shape seen in ClFe(III)(OEP), and the N(4) coordination environment possesses a slight rectangular distortion. These high-spin, mono-meso-substituted iron(III) complexes display (1)H NMR spectra in chloroform-d solution which indicate that the conformational changes seen in the solid-state structures are altered by normal molecular motion to produce spectra consistent with C(s) molecular symmetry. In pyridine solution the high-spin six-coordinate complexes [(py)ClFe(III)(meso-R-OEP)] form. In methanol solution in the presence of excess potassium cyanide, the low-spin six-coordinate complexes K[(NC)(2)Fe(III)(meso-R-OEP)] form. The (1)H NMR spectra of these show that electron-donating substituents produce an upfield relocation of the meso-proton chemical shifts. This relocation is interpreted in terms of increased contribution from the less common (d(xz),d(yz))(4)(d(xy))(1) ground electronic state as the meso substituent becomes more electron donating.