Eosin, blue LEDs and DIPEA are employed in a simple synthesis of (poly)cyclic ,- and ,-acetals.

A simple procedure for the synthesis of (poly)cyclic ,- and ,-acetals from various enol ethers, -acyl enamines or Boc-protected enamines has been developed. The key step is a photocatalytic Stork-Ueno-type cylization using the very simple metal-free conditions of catalytic eosin, diisopropylamine in the green solvent ethanol with blue LED irradition.

The Rapid Synthesis of Colibactin Warhead Model Compounds Using New Metal-Free Photocatalytic Cyclopropanation Reactions Facilitates the Investigation of Biological Mechanisms.

Herein, we report the synthesis of a series of colibactin warhead model compounds using two newly developed metal-free photocatalytic cyclopropanation reactions. These mild cyclopropanations expand the known applications of eosin within synthesis. A halogen atom transfer reaction mode has been harnessed so that dihalides can be used as the cyclopropanating agents.

Multiphotocatalyst Cascades: From Furans to Fused Butyrolactones and Substituted Cyclopentanones.

High value oxygenated polycycles have been rapidly and efficiently accessed from simple precursors in one pot processes. The reported methodology relies on a new and mild method for butenolide synthesis mediated by thiols. The initial photooxygenation and butenolide synthesis have been merged with subsequent photoredox reactions to achieve rare dual-photocatalyst cascades affording various fused butyrolactones.

Access to high value sp-rich frameworks using photocatalyzed [2 + 2]-cycloadditions of γ-alkylidene-γ-lactams.

By harnessing an energy transfer process, new photocatalyzed [2 + 2]-cycloadditions occurring between γ-alkylidene-γ-lactams and unsaturated substrates have been developed. The reaction mode is particularly powerful because it leads to the formation of different high value sp-rich frameworks and further diversity can be introduced through cascade sequences wherein strain releasing opening of the cyclobutane intermediates gives access to complex polycyclic alkaloid frameworks.

Sequential Visible Light-Induced Reactions Using Different Photocatalysts: Transformation of Furans into 2-Pyridones via γ-Lactams Using a New Ring Expansion Reaction.

A new photocatalytic ring expansion reaction that transforms γ-lactams into 2-pyridones is described. The reaction is radical-triggered and was inspired by a late-stage oxidation commonly observed in fungal metabolism. The reaction is particularly powerful because it can be included in a one pot process which converts readily accessible furans directly into 2-pyridones through sequential photo-induced reactions (energy transfer and electron transfer).

One-Pot Transformation of Furans into 1-Azaspirocyclic Alkaloid Frameworks Induced by Visible Light.

High-value 1-azaspirocyclic scaffolds have been made from simple and readily accessible furan precursors in a single operation. The protocol is a one-pot sequence using highly sustainable conditions (oxygen, visible light, and a favored green solvent) that leads to a dramatic increase in molecular complexity. The initial substrates can include functionalities that are suitable for further elaboration; in this way, the pruned polycyclic skeletons of the stemonamine, cylindricine, and lepadiformine natural products were rapidly accessed.

5-Hydroxy-pyrrolone based building blocks as maleimide alternatives for protein bioconjugation and single-site multi-functionalization.

Recent dramatic expansion in potential uses of protein conjugates has fueled the development of a wide range of protein modification methods; however, the desirable single-site multi-functionalization of proteins has remained a particularly intransigent challenge. Herein, we present the application of 5-hydroxy-1,5-dihydro-2-pyrrol-2-ones (5HP2Os) as advantageous alternatives to widely used maleimides for the chemo- and site-selective labeling of cysteine residues within proteins. A variety of 5HP2O building blocks have been synthesized using a one-pot photooxidation reaction starting from simple and readily accessible furans and using visible light and oxygen.

Eosin: a versatile organic dye whose synthetic uses keep expanding.

Organic dyes, which absorb light in the visible region of the electromagnetic spectrum, offer a lower cost, greener alternative to precious metals in photocatalysis. In this context, the organic dye eosin's uses are currently expanding at a significant rate. For a long time, its action as an energy transfer agent dominated, more recently, however, there has been a growing interest in its potential as an electron transfer agent.

Multi-Photocatalyst Cascades: Merging Singlet Oxygen Photooxygenations with Photoredox Catalysis for the Synthesis of Alkaloid Frameworks.

The development of photocascades that rapidly transform simple and readily accessible furan substrates into polycyclic alkaloid frameworks or erythrina natural products is described. Each of the sequences developed makes use of photocatalyzed energy transfer processes, which generate singlet oxygen, to set up the substrates for the second photocatalyzed reaction, wherein electron transfer generates carbon-centered radicals for the cyclizations that give the final complex frameworks. A chemical switch has been developed that can "switch off" one photocatalyst; thus, allowing a second photocatalyst to take over control of the sequence.

Merging singlet-oxygen induced furan oxidations with organocatalysis: synthesis of enantiopure cyclopentanones and hydrindanes.

A new methodology is described herein which converts simple and readily accesible furan substrates into complex enantio-enriched carbocyclic skeletons through the implementation of a simple one-pot procedure. Singlet oxygen furan photoxygenation affords an enedione which then participates in an organocatalysed double-Michael reaction with an enal to furnish a cyclopentanone structure with up to four new contiguous stereogenic centres. The enantioselectivity and diastereoselectivity of this process are both excellent.

The reticent tautomer: exploiting the interesting multisite and multitype reactivity of 4-pyrrolin-2-ones.

4-Pyrrolin-2-ones are a lesser known tautomeric relative of the 3-pyrrolin-2-ones. Despite their infrequent appearance in the literature, they are very interesting and useful compounds. They have highly controllable, multisite and multitype reactivities which are covered in this review.

Singlet-Oxygen-Mediated Synthesis of Pandanusine A and Pandalizine C and Structural Revision of Pandanusine B.

The first synthesis of racemic pandanusines A and B and pandalizine C, isolated from , is reported. The key synthetic step is an efficient tandem reaction sequence initiated by the photooxidation of an easily prepared furylalkylamine precursor. In this reaction sequence, methylene blue plays a dual catalytic role of photosensitizer and redox catalyst, first in generating singlet oxygen and second in facilitating a triplet oxygen reaction.

Vinylogous Reactivity of Cyclic 2-Enones: Organocatalysed Asymmetric Addition to 2-Enals to Synthesize Fused Carbocycles.

A method for asymmetric and site selective annulations at the γ and γ' positions of cyclic 2-enones with α,β-unsaturated aldehydes has been developed. The organocatalysed [3+3]-annulations proceed with high levels of regio-, diastereo-, and enantioselectivity, affording a series of high value fused carbocycles. Further elaboration gave key lactones (both bridged and fused).

One-Pot Synthesis of Diverse γ-Lactam Scaffolds Facilitated by a Nebulizer-Based Continuous Flow Photoreactor.

The use of a modified prototype continuous flow reactor (CFR) as a pivotal part of a number of versatile singlet oxygen-mediated reaction sequences is presented herein. These sequences target rapid access to structural complexity and diversity. The prototype reactor achieves high conversions and productivities by attaining large specific surface areas for these biphasic reactions.

The Power of Triplet and Singlet Oxygen in Synthesis: 2-Oxindoles, 3-Hydroxy-2-oxindoles, and Isatins from Furans.

A straightforward synthesis of substituted 2-oxindoles, 3-hydroxy-2-oxindoles, and isatins has been developed. Easily accessible furans were transformed into tetrahydropyranopyrrolones by a singlet oxygen initiated cascade reaction sequence. An acid-catalyzed rearrangement, followed by aromatization, gave access to a variety of 2-oxindole motifs, which were oxidized to 3-hydroxy-2-oxindoles or isatins using methylene blue as a radical initiator and molecular oxygen as a terminal oxidant.

Asymmetric and Site-Selective [3 + 2]-Annulations for the Synthesis of High-Value Bicyclic Lactams.

Asymmetric and site-selective formal [3 + 2]-annulations of γ-alkyl-β,γ-unsaturated γ-lactams with α,β-unsaturated aldehydes have been developed. These organocatalysed transformations yield high value enantioenriched bicyclic γ-lactams with up to four new stereocenters (sometimes including a quarternary carbon). The overall transformation starts from simple and readily accessible furans and oversees a rapid, controlled, and dramatic enhancement in 3D complexity.

Synthesis of cyclopent-2-enones from furans using a nebulizer-based continuous flow photoreactor.

A series of hydroxycyclopent-2-enones and methoxycyclopent-2-enones have been synthesized in a single operation from simple furan substrates using an innovative continuous flow nebulizer system (NebPhotOX). Photooxygenation of the furan substrates takes place in an aerosol within the NebPhotOX system.

One-Pot Transformation of Simple Furans into Octahydroindole Scaffolds.

A highly efficient and general singlet-oxygen-initiated one-pot transformation of readily accessible furans into octahydroindole scaffolds has been developed.

Total Synthesis and Structural Revision of (+)-Yaoshanenolide B.

(+)-Yaoshanenolide B was synthesized employing as a key step an endo- and face-selective Diels-Alder reaction between natural R-(-)-α-phellandrene and the exocyclic double bond of a 5-methylene-2(5H)-furanone. The dienophile furanone was prepared by photooxygenation of a suitably substituted 2-thiophenylfuran followed by dehydration of the resulting γ-hydroxybutenolide. Through this synthesis, the initially proposed structure for (+)-yaoshanenolide B has been revised to the 1R,2S,4R,7R,1″S diastereomer.

Regiocontrolled Synthesis of γ-Hydroxybutenolides via Singlet Oxygen-Mediated Oxidation of 2-Thiophenyl Furans.

Photooxygenation of 2-thiophenyl-substituted furans in ethanol leads to the rapid, regiocontrolled, and quantitative synthesis of γ-hydroxybutenolides. The carbonyl group in butenolide holds the position of thiophenyl moiety in reacting furans. Decomposition of the initially formed [4 + 2] endoperoxide into products through a radical chain mechanism is proposed, as the fate of thiophenyl moiety is its transformation into ethyl phenylsulfenate (PhS-OEt) and diphenyldisulfide.

Singlet Oxygen-Induced Furan Oxidation for Site-Specific and Chemoselective Peptide Ligation.

A novel chemoselective ligation methodology has been developed for the facile construction of peptide-based fluorescent probes. Furan-containing peptides were activated by singlet oxygen and covalently engaged by nitrogen nucleophiles to yield stable conjugates. Singlet oxygen was compatible with sensitive amino acid residues within the peptides and a range of fluorophores, bearing different functionalities, were successfully incorporated, illustrating the broad scope of the developed strategy.

Photooxygenation of Furylalkylamines: Easy Access to Pyrrolizidine and Indolizidine Scaffolds.

A highly adaptable method targeting the ubiquitous and very important pyrrolizidine and indolizidine scaffolds is presented. The general synthetic utility of the method is underscored by its application to the rapid and easy synthesis of five natural products starting from readily accessible alkylfuran precursors. These unprotected primary furylalkylamines are subjected to photooxygenation conditions, which initiate a complex cascade reaction sequence concluding with the production of high value motifs.

First Total Synthesis of Pandamarine.

The first total synthesis of pandamarine, an alkaloid isolated from Pandanus amaryllifolius is reported. The key step of this extremely short (six steps in total) and protecting group-free synthesis is a highly efficient cascade reaction sequence initiated by the photooxidation of an easily accessible and symmetric difuran precursor.

Methylene Blue as a Photosensitizer and Redox Agent: Synthesis of 5-Hydroxy-1H-pyrrol-2(5H)-ones from Furans.

A highly efficient and general singlet-oxygen-initiated one-pot transformation of readily accessible furans into 5-hydroxy-1H-pyrrol-2(5H)-ones has been developed. The methodology was extended to the synthesis of other high-value α,β-unsaturated γ-lactams. This useful set of transformations relies not only on the photosensitizing ability of methylene blue, but also on its redox properties: properties that have until now been virtually ignored in a synthetic context.

cis-Semihydrogenation of alkynes with amine borane complexes catalyzed by gold nanoparticles under mild conditions.

Supported gold nanoparticles catalyze the semihydrogenation of alkynes to alkenes with ammonia borane or amine borane complexes in excellent yields and under mild conditions. Internal alkynes provide cis-alkenes, making this protocol an attractive alternative of the classical Lindlar's hydrogenation.