Direct decarboxylative Giese amidations: photocatalytic vs. metal- and light-free.

A direct intermolecular decarboxylative Giese amidation reaction from bench stable, non-toxic and environmentally benign oxamic acids has been developed, which allows for easy access to 1,4-difunctionalised compounds which are not otherwise readily accessible. Crucially, a more general acceptor substrate scope is now possible, which renders the Giese amidation applicable to more complex substrates such as natural products and chiral building blocks. Two different photocatalytic methods (one via oxidative and the other via reductive quenching cycles) and one metal- and light-free method were developed and the flexibility provided by different conditions proved to be crucial for enabling a more general substrate scope.

Direct Minisci-Type C-H Amidation of Purine Bases.

A method for the C-H carboxyamidation of purines has been developed that is capable of directly installing primary, secondary, and tertiary amides. Previous Minisci-type investigations on purines were limited to alkylations and arylations. Herein, we present the first method for the direct C-H amidation of a wide range of purines: xanthine, guanine, and adenine structures, including guanosine- and adenosine-type nucleosides. The Minisci-type reaction is also metal-free, cheap, operationally simple, scalable, and applicable to late-stage functionalizations of biologically important molecules.

Direct decarboxylative Giese reactions.

The quest to find milder and more sustainable methods to generate highly reactive, carbon-centred intermediates has led to a resurgence of interest in radical chemistry. In particular, carboxylic acids are seen as attractive radical precursors due their availability, low cost, diversity, and sustainability. Moreover, the corresponding nucleophilic carbon-radical can be easily accessed through a favourable radical decarboxylation process, extruding CO2 as a traceless by-product. This review summarizes the recent progress on using carboxylic acids directly as convenient radical precursors for the formation of carbon-carbon bonds via the 1,4-radical conjugate addition (Giese) reaction.

Direct Hydrodecarboxylation of Aliphatic Carboxylic Acids: Metal- and Light-Free.

A mild and inexpensive method for direct hydrodecarboxylation of aliphatic carboxylic acids has been developed. The reaction does not require metals, light, or catalysts, rendering the protocol operationally simple, easy to scale, and more sustainable. Crucially, no additional H atom source is required in most cases, while a broad substrate scope and functional group tolerance are observed.

Direct C-H Functionalization of Phenanthrolines: Metal- and Light-Free Dicarbamoylations.

A direct method for C-H dicarbamoylations of phenanthrolines has been developed, which is capable of directly installing primary, secondary as well as tertiary amides. This is a significant improvement on the previous direct method, which was limited to primary amides. The metal-, light-, and catalyst-free Minisci-type reaction is cheap, operationally simple, and scalable. We demonstrate that the step efficiency toward dicarbamoylated phenanthroline targets can now be significantly improved.

Expanding the Tool Kit of Automated Flow Synthesis: Development of In-line Flash Chromatography Purification.

Recent advancements in in-line extraction and purification technology have enabled complex multistep synthesis in continuous flow reactor systems. However, for the large scope of chemical reactions that yield mixtures of products or residual starting materials, off-line purification is still required to isolate the desired compound. We present the in-line integration of a commercial automated flash chromatography system with a flow reactor for the continuous synthesis and isolation of product(s). A proof-of-principle study was performed to validate the system and test the durability of the column cartridges, performing an automated sequence of 100 runs over 2 days. Three diverse reaction systems that highlight the advantages of flow synthesis were successfully applied with in-line normal- or reversed-phase flash chromatography, continuously isolating products with 97-99% purity. Productivity of up to 9.9 mmol/h was achieved, isolating gram quantities of pure product from a feed of crude reaction mixture. Herein, we describe the development and optimization of the systems and suggest guidelines for selecting reactions well suited to in-line flash chromatography.

Selectivity Control in Gold-Catalyzed Hydroarylation of Alkynes with Indoles: Application to Unsymmetrical Bis(indolyl)methanes.

Gold-catalyzed hydroarylation of unactivated alkynes with indoles have previously been reported to proceed with double indole addition to produce symmetrical bis(indolyl)methanes (BIMs). We demonstrate for the first time that the selectivity of the gold-catalyzed reaction can be fully switched to allow for isolation of the vinylindole products instead. Furthermore, this selective reaction can be utilized to synthesize the more difficult to access unsymmetrical BIMs from readily available starting materials.

Heterogeneous photocatalysis in flow chemical reactors.

The synergy between photocatalysis and continuous flow chemical reactors has shifted the paradigms of photochemistry, opening new avenues of research with safer and scalable processes that can be readily implemented in academia and industry. Current state-of-the-art photocatalysts are homogeneous transition metal complexes that have favourable photophysical properties, wide electrochemical redox potentials, and photostability. However, these photocatalysts present serious drawbacks, such as toxicity, limited availability, and the overall cost of rare transition metal elements. This reduces their long-term viability, especially at an industrial scale. Heterogeneous photocatalysts (HPCats) are an attractive alternative, as the requirement for the separation and purification is largely removed, but typically at the cost of efficiency. Flow chemical reactors can, to a large extent, mitigate the loss in efficiency through reactor designs that enhance mass transport and irradiation. Herein, we review some important developments of heterogeneous photocatalytic materials and their application in flow reactors for sustainable organic synthesis. Further, the application of continuous flow heterogeneous photocatalysis in environmental remediation is briefly discussed to present some interesting reactor designs that could be implemented to enhance organic synthesis.

Availability of orchid mycorrhizal fungi on roadside trees in a tropical urban landscape.

Urban expansion threatens biodiversity worldwide, therefore urban spaces need to be amenable to biodiversity conservation. On trees in urban environments, natural colonisation and successful translocation of epiphytic orchids are necessary to enhance urban biodiversity, and depend on the availability of compatible orchid mycorrhizal fungi (OMF). However, the extent of OMF presence and distribution, as well as niche requirements for the OMF, remain poorly studied. To identify and quantify OMF on urban trees as well as assess their suitability for native epiphytic orchids, we conducted high-throughput sequencing on tree bark and orchid root samples. OMF were detected at 60% of the study sites on 16% of 270 bark samples (from stem, fork, and branch microsites within each tree). OMF presence and richness on bark samples were related to multiple biophysical factors; in general, humus presence and precipitation levels were positively predictive of OMF presence and richness. We found Ceratobasidiaceae- and Serendipitaceae-associated OMF both on bark and within roots. Orchid species also showed differing mycorrhizal specificity. Sites associated with fungal genera Ceratobasidium, Rhizoctonia, and Serendipita were considered suitable habitats for seven orchid species. The results suggest that urban trees support OMF and are therefore suitable for native orchid species; however, OMF availability are largely constrained by biophysical factors. To maximise the likelihood of translocation success and consequent natural establishment, we propose that (micro)sites are screened for compatible OMF prior to any intervention.

Synthesis and optoelectronic properties of benzoquinone-based donor-acceptor compounds.

Herein, we report a mild and efficient palladium-catalyzed C-H functionalization method to synthesize a series of benzoquinone (BQ)-based charge-transfer (CT) derivatives in good yields. The optoelectronic properties of these compounds were explored both theoretically and experimentally and correlations to their structures were identified as a function of the nature and position of the donor group (meta and para) attached to the benzoquinone acceptor. Compound 3, where benzoquinone is para-conjugated to the diphenylamine donor group, exhibited thermally activated delayed fluorescence (TADF) with a biexponential lifetime characterized by a prompt ns component and a delayed component of 353 µs.

Pd(II)-Catalyzed Enantioselective Desymmetrization of Polycyclic Cyclohexenediones: Conjugate Addition versus Oxidative Heck.

Pd(II)-catalyzed desymmetrization of polycyclic cyclohexenediones has been achieved with high enantio- and diastereoselectivities. Up to five contiguous stereocenters are desymmetrized, while simultaneously, an additional stereocenter is created by the enantioselective conjugate addition. Surprisingly, the conjugate addition products dominate even under typical oxidative Heck conditions, and these observations may provide some insight into the competition between the two related reactions.

Metal-, Photocatalyst-, and Light-Free Direct C-H Acylation and Carbamoylation of Heterocycles.

Direct C-H acylations and carbamoylations of heterocycles can now be readily achieved without requiring any conventional metal, photocatalyst, electrocatalysis, or light activation, thus significantly improving on sustainability, costs, toxicity, waste, and simplicity of the operational procedure. These mild conditions are also suitable for gram-scale reactions and late-stage functionalizations of complex molecules, including pharmaceuticals, N,N-ligands, and light-sensitive molecules.

Dual copper- and photoredox-catalysed C(sp2)-C(sp3) coupling.

The use of copper catalysis with visible light photoredox catalysis in a cooperative fashion has recently emerged as a versatile means of developing new C-C bond forming reactions. In this work, dual copper and photoredox catalysis is exploited to effect C(sp2)-C(sp3) cross-couplings between aryl boronic acids and benzyl bromides.

Metal-, Photocatalyst-, and Light-Free, Late-Stage C-H Alkylation of Heteroarenes and 1,4-Quinones Using Carboxylic Acids.

Contrary to the accepted convention, this work shows that Minisci-type C-H alkylation does not require any metal, photocatalyst, light, or prefunctionalization of the readily available and inexpensive carboxylic acids to proceed well under mild conditions. These mild conditions can be utilized for late-stage alkylations of complex molecules, including pharmaceutical compounds and light-sensitive compounds which degrade under photocatalytic conditions.

Gold(I)-Catalysed Hydroarylation of 1,3-Disubstituted Allenes with Efficient Axial-to-Point Chirality Transfer.

Hydroarylation of enantioenriched 1,3-disubstituted allenes has the potential to proceed with axial-to-point chirality transfer to yield enantioenriched allylated (hetero)aryl compounds. However, the gold-catalysed intermolecular reaction was previously reported to occur with no chirality transfer owing to competing allene racemisation. Herein, we describe the development of the first intermolecular hydroarylations of allenes to proceed with efficient chirality transfer and summarise some of the key criteria for achieving high regio- and stereoselectivity.

Rapid Iododeboronation with and without Gold Catalysis: Application to Radiolabelling of Arenes.

Radiopharmaceuticals that incorporate radioactive iodine in combination with single-photon emission computed tomography imaging play a key role in nuclear medicine, with applications in drug development and disease diagnosis. Despite this importance, there are relatively few general methods for the incorporation of radioiodine into small molecules. This work reports a rapid air- and moisture-stable ipso-iododeboronation procedure that uses NIS in the non-toxic, green solvent dimethyl carbonate. The fast reaction and mild conditions of the gold-catalysed method led to the development of a highly efficient process for the radiolabelling of arenes, which constitutes the first example of an application of homogenous gold catalysis to selective radiosynthesis. This was exemplified by the efficient synthesis of radiolabelled meta-[125 I]iodobenzylguanidine, a radiopharmaceutical that is used for the imaging and therapy of human norepinephrine transporter-expressing tumours.

Auto-Tandem Catalysis: PdII -Catalysed Dehydrogenation/Oxidative Heck Reaction of Cyclopentane-1,3-diones.

A PdII catalyst system has been used to successfully catalyse two mechanistically distinct reactions in a one-pot procedure: dehydrogenation of 2,2-disubstituted cyclopentane-1,3-diones and the subsequent oxidative Heck coupling. This auto-tandem catalytic reaction is applicable to both batch and continuous flow processes, with the latter being the first example of a tandem aerobic dehydrogenation/oxidative Heck in flow. In addition, a telescoped reaction involving enantioselective desymmetrisation of the all-C quaternary centre was successfully achieved.

Chirality Transfer in Gold(I)-Catalysed Hydroalkoxylation of 1,3-Disubstituted Allenes.

Gold(I)-catalysed intermolecular hydroalkoxylation of enantioenriched 1,3-disubstituted allenes was previously reported to occur with poor chirality transfer due to rapid allene racemisation. The first intermolecular hydroalkoxylation of allenes with efficient chirality transfer is reported here, exploiting conditions that suppress allene racemisation. A full substrate scope study reveals that excellent regio- and stereoselectivities are achieved when a σ-withdrawing substituent is present.

Dual gold photoredox C(sp(2))-C(sp(2)) cross couplings - development and mechanistic studies.

A dual visible light photoredox and gold-catalysed C(sp(2))-C(sp(2)) cross coupling is described. The success of this mild, oxidant- and base-free cross coupling is highly dependent on the amount of water added. Mechanistic studies show two distinct pathways depending on the gold catalyst employed: transmetallation of the arylboronic acid with gold(i) occurs prior to oxidation of gold(i) to gold(iii) using cationic gold(i) catalysts, whereas oxidation of gold(i) to gold(iii) precedes transmetallation using neutral gold(i) catalysts.