The Quinine Odyssey: A Barometer of the State of Organic Synthesis Over Centuries.

The year 2024 marks the 80th anniversary of the landmark formal synthesis of (±)-quinine completed by Woodward and Doering. This article examines the evolution of approaches to access this storied Cinchona alkaloid natural product which represent a microcosm the progress that has been made in organic synthesis over the past ~170 years. Seminal contributions led by Pasteur, Rabe, Woodward, Uskokovic, Stork, Jacobsen, Hayashi, Maulide and others are discussed.

High-Efficiency Solar Transformation of Sugars via a Heterogenous Gallium(III) Catalyst.

Extremely limited research exploring the photocatalytic potential of main group metals, such as aluminum, gallium, and tin, has been undertaken due to their weak light harvesting properties. This study reports the efficient transformation of sugars to 5-hydroxymethylfurfural (HMF) with high yield employing an original heterogeneous photocatalyst comprising a gallium(III) complex immobilized on an alumina support. Under visible light irradiation, the reaction rate of HMF formation is ~143 times higher than the equivalent thermal reaction performed in the absence of light. The turnover number (TON) of the heterogeneous gallium(III) photocatalyst was as high as 1500, which was ca. two orders of magnitude higher than the TON of the homogeneous gallium(III) system. It is proposed that photoirradiation significantly enhances the Lewis acidity of the catalyst by forming a semi-coordination state between gallium(III) and N-donor ligands, enabling the increased interaction of reactant sugar molecules with gallium(III) active sites. Consistent with this, the photoresponsive coordination of the gallium(III) complex and the abstraction of the hydroxy group by the metal under irradiation with visible light is observed by NMR spectroscopy for the first time. These findings demonstrate that efficient photocatalysts derived from the main group elements can facilitate biomass conversion using visible light.

Electrochemically Generated Carbocations in Organic Synthesis.

This Minireview examines a selection of case studies that showcase distinctive and enabling electrochemical approaches that have allowed for the generation and reaction of carbocation intermediates under mild conditions. Particular emphasis is placed on the progress that has been made in this area of organic synthesis and polymer chemistry over the past decade.

Lawesson's Reagent: Providing a New Approach to the Forgotten 6-Thioverdazyl Radical.

A new method for the preparation of the underrepresented 1,5-dimethyl-6-thioverdazyl radicals has been developed employing Lawesson's reagent (LR). The synthetic route involves the direct thionation of the carbonyl group of the corresponding dialkylbishydrazone followed by cyclization to give the tetrazinanthione verdazyl precursor on a gram scale. Subsequent oxidation yields the 6-thioverdazyl radical. It was determined that thionation of substrates containing electron-withdrawing groups in the ortho- or para-positions was high yielding. In contrast, for the parent phenyl group or substrates bearing weakly electron-donating substituents, thionation efficiency was significantly reduced. This could be overcome by utilizing partial in situ cyclization, which occurs during work up, to generate the tetrazinanthione directly via a one-pot synthesis. Density functional theory suggests that the LR fragment interacts with the carbonyl prior to cycloaddition and subsequent to cycloreversion, leading to the thiocarbonyl. The electronic nature of the radical is characterized with electron paramagnetic resonance as well as the first report of 6-thioverdazyl redox properties.

"Dissolve-on-Demand" 3D Printed Materials: Polymerizable Eutectics for Generating High Modulus, Thermoresponsive and Photoswitchable Eutectogels.

Solvent-free photopolymerization of vinyl monomers to produce high modulus materials with applications in 3D printing and photoswitchable materials is demonstrated. Polymerizable eutectic (PE) mixtures are prepared by simply heating and stirring various molar ratios of N-isopropylacrylamide (NIPAM), acrylamide (AAm) and 2-hydroxyethyl methacrylate (HEMA). The structural and thermal properties of the resulting mixtures are evaluated by 1D and 2D NMR spectroscopy as well as differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). UV photocuring kinetics of the PE mixtures is evaluated via in situ photo-DSC and photorheology measurements. The PE mixtures cure rapidly and display storage moduli that are orders of magnitude greater than equivalent copolymers cured in an aqueous medium. The versatility of these PE systems is demonstrated through the addition of a photoswitchable spiropyran acrylate monomer, as well as applying the PE formulation as a stereolithography (SLA)-based 3D printing resin. Due to the hydrogen-bonding network in PE systems, 3D printing of the eutectic resin is possible in the absence of crosslinkers. The addition of a RAFT agent to reduce average polymer chain length enables 3D printing of materials which retain their shape and can be dissolved on demand in appropriate solvents.

Correction: Acridine-based copper(I) PNP pincer complexes: catalysts for alkyne hydroboration and borylation of aryl halides.

Correction for 'Acridine-based copper(I) PNP pincer complexes: catalysts for alkyne hydroboration and borylation of aryl halides' by Angus Olding et al., Dalton Trans., 2024, 53, 4471-4478, https://doi.org/10.1039/D3DT04269C.

Photochemical Povarov-type Reactions: Electron Donor-Acceptor Photoactivation by Visible Light.

This report investigates the mechanism of photochemical Povarov-type reactions of N,N-dialkylanilines and maleimides in polar solvents (DMF or dioxane) in the presence of light. Fundamental aspects of the electron donor-acceptor (EDA) photoactivation pathway proposed to underpin this chemistry are examined through integrated experimental and computational studies. This approach provided evidence supporting the involvement of an EDA complex in facilitating this chemistry via a reaction mechanism that does not involve a triplet manifold. Most notably, our findings indicate that relying solely on UV-vis absorption spectroscopic data to either account for or predict reactivity in synthetic experiments may not always provide the complete picture. More specifically, this relates to considering UV-vis absorption spectroscopic data, calculated values for association constants (KEDA) and molar extinction coefficients (ε), with the reactivity observed in associated synthetic reactions in practice.

Acridine-based copper(I) PNP pincer complexes: catalysts for alkyne hydroboration and borylation of aryl halides.

PNP pincers represent some of the most well-studied ligand systems in coordination chemistry owing to their high thermal and chemical stability, and the predictable metal coordination geometries of associated metal complexes. Examples of first-row transition metal complexes bearing acridine-based PNP pincer ligands are extremely rare. This study reports the preparation and structural authentication of acridine-based copper(I) PNP complexes, which reveal the profound effects that the steric bulk of methylene-tethered P-substituents has on metal centre coordination number and geometry. The capacity of these systems to mediate copper-catalysed alkyne hydroboration and the borylation of aryl halides is also investigated.

Advancing Gold Redox Catalysis: Mechanistic Insights, Nucleophilicity-Guided Transmetalation, and Predictive Frameworks for the Oxidation of Aryl Gold(I) Complexes.

Gold redox catalysis, often facilitated by hypervalent iodine(III) reagents, offers unique reactivity but its progress is mainly hindered by an incomplete mechanistic understanding. In this study, we investigated the reaction between the gold(I) complexes [(aryl)Au(PR3 )] and the hypervalent iodine(III) reagent PhICl2 , both experimentally and computationally and provided an explanation for the formation of divergent products as the ligands bonded to the gold(I) center change. We tackled this essential question by uncovering an intriguing transmetalation mechanism that takes place between gold(I) and gold(III) complexes. We found that the ease of transmetalation is governed by the nucleophilicity of the gold(I) complex, [(aryl)Au(PR3 )], with greater nucleophilicity leading to a lower activation energy barrier. Remarkably, transmetalation is mainly controlled by a single orbital - the gold dx 2 -y 2 orbital. This orbital also has a profound influence on the reactivity of the oxidative addition step. In this way, the fundamental mechanistic basis of divergent outcomes in reactions of aryl gold(I) complexes with PhICl2 was established and these observations are reconciled from first principles. The theoretical model developed in this study provides a conceptual framework for anticipating the outcomes of reactions involving [(aryl)Au(PR3 )] with PhICl2 , thereby establishing a solid foundation for further advancements in this field.

Distinctive Arbutin-Containing Markers: Chemotaxonomic Significance and Insights into the Evolution of Proteaceae Phytochemistry.

Natural products isolation studies of eight endemic Tasmanian Proteaceae species - Agastachys odorata, Persoonia juniperina, Hakea megadenia, Hakea epiglottis, Orites diversifolius, Orites acicularis, Orites revolutus, and Telopea truncata - and three endemic Australian Proteaceae species Banksia serrata, Banksia praemorsa, and Banksia marginata were undertaken. Two previously unreported glycoside-derived natural products were identified, in addition to four other tremendously rare arbutin esters. The results of this study provide further evidence consistent with the proposal that these distinctive arbutin esters represent markers that can provide valuable insights into the chemical evolution of plant species within the family Proteaceae.

Furanosesquiterpenes and Related Natural Products from Myoporum Species: Isolation and Semisynthesis.

Myoporum species are recognized as toxic plants. Essential oils from the leaves of these species contain furanosesquiterpenes, which comprise the active toxins. In this report, natural products isolation studies of three Myoporum species (M. insulare, M. parvifolium, and M. montanum) afforded two previously unreported furanosesquiterpenes (24 and 25) and three unprecedented γ-lactone-containing analogues (26-28), along with nine previously reported furanosesquiterpenes and five other natural products. Among the 14 furanosesquiterpenes and related compounds isolated in this study, we observed three distinct types of furanosesquiterpene structures isolated from each of these Myoporum species. Semisyntheses of four sesquiterpene natural products were completed from (-)-ngaione over two steps in each case. This included the synthesis of the lactam-containing sesquiterpene myoporumine A.

Dipole-Transmissive 1,3-Dipolar Cycloadditions for the Rapid Construction of Polycyclic N-Heterocycles: Synthetic and Mechanistic Investigations.

The investigation of distinctive dipole-transmissive dipolar cycloaddition (DTDC) methodology and the formalisation of this concept is reported. A DTDC procedure was able to be developed by taking advantage of the structural complementarity of azide and diazoalkane 1,3-dipoles. Intramolecular azide-alkene 1,3-DCs followed by spontaneous dipole transmission upon work-up furnished intermediate α-diazoisoindole and α-diazoisoquinoline substrates bearing the key secondary diazoalkane 1,3-dipole. N-Derivatisation of the intermediate α-diazoisoindole and α-diazoisoquinolines with a tethered secondary dipolarophile followed by a subsequent 1,3-DC allowed for rapid construction of a range of functionalised polycyclic N-heterocycles. Integrated experimental and theoretical studies established requirements for product formation and revealed the likely mechanistic basis of divergent reactivity observed.

Structural authentication of intermediates of mechanistic significance in palladium- and nickel-catalysed cross-couplings: case studies.

This article examines a selection of case studies that highlight key strategies that have enabled the structural authentication of important species that shed light on fundamental on-cycle intermediates in palladium- and nickel-catalysed C-C, C-N, and C-O cross-coupling reactions. Particular emphasis is placed on studies in which the structures of rather intractable intermediates have been confirmed unambiguously by X-ray crystallography, while also contextualising the mechanistic insights that these reports have contributed.

Pretransmetalation Intermediates in Suzuki-Miyaura Cross-Couplings: Synthesis of Csp3-, Csp2- and Csp-Organopalladium(II) Boronates.

Organopalladium(II) boronates represent fundamental pretransmetalation intermediates in Suzuki-Miyaura cross-couplings. These species are typically kinetically unstable, making them particularly elusive. In this study, a range of unprecedented, kinetically stable alkyl-, alkenyl-, allenyl-, and alkynylpalladium(II) boronates were prepared from various Csp3, Csp2, and Csp electrophiles via a simple, general method. The structures of these complexes were secured by X-ray crystallography, and the chemical competence of a number of these intermediates in transmetalation was demonstrated.

Strategies for the synthesis of Stemona alkaloids: an update.

Covering: 2009 to 2022The Stemona alkaloids, which are found in plant species from the family Stemonaceae, represent a tremendously large and structurally-diverse family of natural products. This review presents and discusses a selection of case studies, grouped by alkaloid class, that showcase the key strategies and overall progress that has been made in the synthesis of Stemona alkaloids and related compounds since 2009. Structural reassignments that have been reported over this period are also identified where necessary.

Discovery of Periodinane Oxy-Assisted (POA) Oxidation Mechanism in the IBX-Controlled Oxidative Dearomatization of Pyrroles Mediated by Acetic Acid.

The 2-iodoxybenzoic acid (IBX)-controlled oxidative dearomatization of pyrroles occurs very slowly (or not all) in many organic solvents, including DMSO in which IBX is soluble. Interestingly, although IBX is only partially soluble in acetic acid, this solvent mediates the pyrrole oxidative dearomatization. With the aid of density functional theory (DFT) calculations, we have discovered a new mode of reactivity, termed the periodinane oxy-assisted (POA) oxidation mechanism, which explains this observation.

Structural Revision of Parvistemoamide: Informing Biosynthetic Proposals of Stemona Alkaloids.

The natural product parvistemoamide was isolated in 1991 and has ostensibly eluded synthesis. Its distinctive assigned structure represents the first and only Stemona alkaloid within its class. For over 30 years, this structure has influenced biosynthetic proposals concerning this family of natural products. Following synthetic studies and comprehensive analysis of relevant literature, a revised structure of parvistemoamide is proposed that is consistent with the fundamental Stemona alkaloid stemoamide.

Rhenium-catalysed reactions in chemical synthesis: selected case studies.

This Perspective presents and discusses a selection of examples that reinforce the enabling and distinctive reactivity provided by homogeneous rhenium catalysis in chemical synthesis. Specifically, the ability for lower oxidation state rhenium-carbonyl catalysts to engage alkyne, allene, and enol substrates in various carbon-carbon bond-forming reactions is highlighted. The inherent capacity of Lewis acidic, higher oxidation state oxorhenium catalysts to facilitate the transposition/isomerisation of allyl alcohols and attendant functionalisation via reaction cascades is also showcased. A brief overview of representative rhenium catalysts that have allowed for reductions of imines, carbonyls, and related compounds is also provided.

Photoactive Metal Carbonyl Complexes Bearing N-Heterocyclic Carbene Ligands: Synthesis, Characterization, and Viability as Photoredox Catalysts.

This report details the synthesis and characterization of a small family of previously unreported, structurally related chromium, molybdenum, tungsten, manganese, and iron complexes bearing N-heterocyclic carbene and carbonyl supporting ligands. These complexes have the general form [ML(CO)3X] or [ML(CO)3], where X = CO or Br and L = 1-phenyl-3-(2-pyridyl)imidazolin-2-ylidene. Where possible, the solid-state, spectroscopic, electrochemical, and photophysical properties of these molecules were studied using a combination of experiment and theory. Photophysical studies reveal that decarbonylation occurs when these complexes are exposed to ultraviolet light, with the CO ligand being replaced with a labile acetonitrile solvent molecule. To obtain insights into the potential utility, scope, and applications of these complexes in visible-light-mediated photoredox catalysis, their capacity to facilitate a range of photoinduced reactions via the reductive or oxidative functionalization of organic molecules was investigated. These chromium, molybdenum, and manganese catalysts efficiently facilitated atom-transfer radical addition processes. In light of their photolability, these types of catalysts may potentially allow for the development of photoinduced reactions involving less conventional inner-sphere electron-transfer pathways.

Natural products isolation studies of the paleoendemic plant species Nothofagus gunnii and Nothofagus cunninghamii.

The first natural product isolation studies of Nothofagus gunnii (Hook.f.) Oerst and Nothofagus cunninghamii (Hook.f.) Oerst have been undertaken. A previously unreported stilbene derivative, pinosylvin monoacetate, was isolated from the leaves of N. gunnii, in addition to 14 known compounds; including the flavonoids galangin, pinobanksin, catechin and quercetin; sesquiterpenoids such as, ilicol and (+)-ß-costol acetate; 2,4-dihydroxy-6-methoxychalcone and pinosylvin. Four known flavonoid natural products, catechin, quercetin, ayanin, and avicularin were isolated from the leaves of N. cunninghamii. This study reveals that N. gunnii is a rich source of flavonoid, chalcone and stilbene compounds, while primarily hydroxyflavonoid compounds are found in N. cunninghamii. The isolated phytochemicals are consistent with the evolutionary relationships suggested to exist among Nothofagus species.