Asymmetric Organocatalyzed Intermolecular Functionalization of Cyclohexanone-Derived Dienones.

Over the past decades, the advent of asymmetric organocatalysis has changed the way chemists think about creating or breaking chemical bonds, enabling new enantioselective strategies for functionalized molecules. The success of asymmetric organocatalysis is notably based on the existence of various activation modes, leading to countless transformations, and on the vast array of available chiral organic catalysts. Breakthroughs in this area have also been driven by selective functionalization of compounds with multiple activation sites such as cyclohexanone-derived dienones. These platforms can undergo diverse transformations such as Michael addition, Friedel-Crafts alkylation or Diels-Alder cycloaddition that offer new opportunities for reaching natural products and biologically relevant compounds. Amongst cyclohexanone-derived dienones, the 2,5-cyclohexadienone motif has received a great deal of attention due to its reactivity pattern and recently, (cross)-conjugated cyclohexanone-derived substrates have also been considered. In this review, we discuss the intermolecular functionalization of (cross)-conjugated cyclohexanone-derived compounds employing asymmetric organocatalysis.

Antibacterial nanophotosensitizers in photodynamic therapy: An update.

Bacterial infections constitute a major challenge of clinical medicine, particularly in specialties such as dermatology and dental medicine. Antiseptics and antibiotics are the main adjunctive therapies to anti-infective procedures in these specialties. However, antibacterial photodynamic therapy (PDT) has been introduced as a novel and promising alternative to conventional antibacterial approaches. PDT relies on the formation of reactive oxygen species (ROS) by a photosensitizer (PS) after activation by a specific light source. Nanotechnology was later introduced to enhance the antibacterial efficacy of PS during PDT. In this review, we describe the different nanoparticles (NPs) used in PDT and their properties. Recent in vivo data of NPs in antibacterial PDT in dermatology and dental medicine and their safety concerns are also reviewed.

Synthesis and Photophysical Characterizations of Pyrroloquinolone Photosensitizers for Singlet Oxygen Production†.

A series of pyrroloquinolone photosensitizers bearing different halogen substituents (Cl, Br, I) on the heterocyclic framework was studied. These structures were readily prepared through a multi-step synthetic sequence involving an oxidative protocol as an important step to access the quinolone framework. Spectroscopic characterizations and computational investigations were carried out to study the dyes before and after the oxidative step. Interestingly, the fluorescence emission was significantly reduced upon oxidation. In spite of a low photostability under UV light, the pyrroloquinolone photosensitizers proved effective to produce singlet oxygen. Higher singlet oxygen quantum yields were obtained with photosensitizers bearing halogen atoms with a higher atomic number.

Rose Bengal Immobilized on Cellulose Paper for Sustainable Visible-Light Photocatalysis.

This work reports the heterogenization of Rose Bengal dye on simple cellulose paper sheets (Cell-RB) through copper-catalyzed azide-alkyne click ligation. The photocatalytic properties of Cell-RB under green LED irradiation were evaluated in a series of dehydrogenative transformations for the functionalization of N-aryltetrahydroisoquinolines and quinoxalin-2(1H)-ones. The excellent photocatalytic activities observed, associated to the ease of recovery with simple tweezers, highlight the strong assets of Cell-RB with respect to traditional homogeneous organic photocatalysts.

Atom Economical Photocatalytic Oxidation of Phenols and Site-Selective Epoxidation Toward Epoxyquinols.

The discovery of a multiple-bond-forming process merging the singlet oxygen-mediated dearomatization of 3,4-disubstitued phenols and diastereo- and regioselective epoxidation is described. This one-pot strategy using a transition metal-free multicatalytic system comprised of rose bengal and cesium carbonate allowed the efficient formation of functionalized epoxyquinol products under mild conditions. Mechanistic investigations have been performed to shed the light on the key species involved in this transformation.

Merging Gradient-Based Methods to Improve Benchtop NMR Spectroscopy: A New Tool for Flow Reaction Optimization.

Emerging low cost, compact NMR spectrometers that can be connected in-line to a flow reactor are suited to study reaction mixtures. The main limitation of such spectrometers arises from their lower magnetic field inducing a reduced sensitivity and a weaker spectral resolution. For enhancing the spectral resolution, the merging of Pure-Shift methods recognized for line narrowing with solvent elimination schemes was implemented in the context of mixtures containing protonated solvents. One more step was achieved to further enhance the resolution power on compact systems, thanks to multiple elimination schemes prior to Pure-Shift pulse sequence elements. For the first time, we were able to remove up to 6 protonated solvent signals simultaneously by dividing their intensity by 500 to 1700 with a concomitant spectral resolution enhancement for signals of interest from 9 to 12 as compared to the standard 1D 1 H. Then, the potential of this new approach was shown on the flow synthesis of a complex benzoxanthenone structure.

Unusual Oxidative Dealkylation Strategy toward Functionalized Phenalenones as Singlet Oxygen Photosensitizers and Photophysical Studies.

A series of functionalized 6-alkoxy phenalenones was prepared through an unprecedented oxidative dealkylation of readily available phenalene precursors. The starting phenalenes were efficiently synthesized via an aminocatalyzed annulation/O-alkylation strategy starting from simple substrates. The spectroscopic properties of some phenalenones were investigated in different solvents. Introducing an alkoxy substituent at the 6-position onto the phenalenone framework results in a red shift of the absorption. The synthesized phenalenones exhibit low fluorescence quantum yields, and the fluorescence decay was studied in different solvents, highlighting the presence of several lifetimes. The singlet oxygen (1O2) photosensitizing propensity of some phenalenones was investigated, and the results showed the striking importance of the phenalenone molecular structure in generating singlet oxygen with high yields. The ability of phenalenones to generate singlet oxygen was then harnessed in three photooxygenation reactions: anthracene oxidation, oxy-functionalization of citronellol through the Schenck-ene reaction, and photooxidation of a diene.

A fully bio-sourced adsorbent of heavy metals in water fabricated by immobilization of quinine on cellulose paper.

The fabrication of a fully bio-sourced adsorbent of Cd(II) by covalent immobilization of quinine on cellulose paper is described. The double bond of commercially available quinine was converted to a terminal alkyne function which was reacted with cellulose paper, chemically modified with azide functions, through a 1,3-dipolar cycloaddition, leading to Cell-Quin. The adsorption efficiency of Cell-Quin was investigated to determine the optimal pH, contact time and dose of adsorbent, ultimately leading to high levels of removal. The mechanism of adsorption of Cell-Quin was deeply rationalized through kinetic experiments and isotherm modeling. We also showed that Cell-Quin could adsorb other heavy metals such as Cu(II), Pb(II), Ni(II) and Zn (II).

Multicatalytic dearomatization of phenols into epoxyquinols via a photooxygenation process.

A multicatalytic photooxygenation of substituted phenols in the presence of rose bengal and cesium carbonate under green LED light is reported. This transformation enabled the introduction of both atoms of singlet oxygen and led to the one-pot synthesis of epoxyquinols in a stereoselective way.

A Fused Hexacyclic Ring System: Diastereoselective Polycyclization of 2,4-Dienals through an Interrupted iso-Nazarov Reaction.

We report an unprecedented domino polycyclization from readily available 2,4-dienals and cyclic α,ß-unsaturated imines that is initiated by an iso-Nazarov reaction. This Brønsted acid promoted reaction enables the concomitant formation of four bonds, three cycles, and four contiguous stereogenic centers to yield elaborated structures in a single operation. A range of fused hexacyclic molecules is obtained in a highly diastereoselective manner.

In Situ Generation of Cyclopentadienol Intermediates from 2,4-Dienals. Application to the Synthesis of Spirooxindoles via a Domino Polycyclization.

An efficient domino polycyclization combining different classes of pericyclic reactions leads to complex spiroxindoles under mild conditions. This domino process represents a rare example of an in situ formation of cyclopentadienol derivatives from an interrupted iso-Nazarov electrocyclization of 2,4-dienals and their use in [4 + 2] cycloaddition reactions. According to the reaction conditions, different polycyclic architectures are obtained in good yields and excellent diastereoselectivities.

One-Pot Synthesis of Functionalized Fused Furans via a BODIPY-Catalyzed Domino Photooxygenation.

Six-membered ring fused furans containing a tetrasubstituted tertiary carbon were prepared in an unprecedented one-pot BODIPY-catalyzed domino photooxygenation/reduction process. A series of functionalized furans was synthesized from readily available 2-alkenylphenols and mechanistic studies were performed to account for the domino photosensitized oxygenation.

Aminocatalyzed Synthesis of Enantioenriched Phenalene Skeletons through a Friedel-Crafts/Cyclization Strategy.

A series of enantioenriched phenalene-derived compounds were accessed by a Friedel-Crafts/cyclization strategy. Starting from α,ß-unsaturated aldehydes and 2-naphthol derivatives, high levels of enantioselectivity were obtained through iminium-enamine catalysis. The catalytic system composed of a diphenylprolinol silyl ether organocatalyst and triethylamine as a base was applied to a combination of diversely functionalized substrates. The obtained phenalene-derived architectures are promising building blocks for reaching natural products and exhibit fluorescence properties.

Sulfamide chemistry applied to the functionalization of self-assembled monolayers on gold surfaces.

Aniline-terminated self-assembled monolayers (SAMs) on gold surfaces have successfully reacted with ArSO2NHOSO2Ar (Ar = 4-MeC6H4 or 4-FC6H4) resulting in monolayers with sulfamide moieties and different end groups. Moreover, the sulfamide groups on the SAMs can be hydrolyzed showing the partial regeneration of the aniline surface. SAMs were characterized by water contact angle (WCA) measurements, Fourier-transform infrared reflection absorption spectroscopy (IRRAS) and X-ray photoelectron spectroscopy (XPS).

Iron-Mediated Domino Interrupted Iso-Nazarov/Dearomative (3 + 2)-Cycloaddition of Electrophilic Indoles.

An efficient domino reaction combining different classes of pericyclic reactions leads to chiral complex polycyclic indoline-based architectures from achiral starting materials under mild conditions. This practical method is based on the ability of iron(III) chloride to promote both 4π electrocyclizations of 2,4-dienals and the C2-C3 umpolung of N-acetylindoles during the dearomative (3 + 2) cycloadditions.

Asymmetric Synthesis of Fused Polycyclic Indazoles through Aminocatalyzed Aza-Michael Addition/Intramolecular Cyclization.

The first example of an asymmetric aminocatalyzed aza-Michael addition of 1H-indazole derivatives to α,ß-unsaturated aldehydes is described. The iminium/enamine cascade process lies at the heart of our strategy, leading to enantioenriched fused polycyclic indazole architectures. Variations on both the α,ß-unsaturated aldehydes and the indazole-7-carbaldehyde heterocycles were studied in order to broaden the scope of the transformation in synthetically interesting directions. The fused polycyclic indazoles exhibit fluorescence properties and can undergo synthetic transformations.

Enantioselective Desymmetrization of para-Quinamines through an Aminocatalyzed Aza-Michael/Cyclization Cascade Reaction.

An unprecedented organocatalytic asymmetric desymmetrization of para-quinamines leading to functionalized hydroindoles, a common motif in many alkaloids, has been reported. The ability of diarylprolinol silyl ethers to promote iminium and enamine activation of α,ß-unsaturated aldehydes in one catalytic cycle is the centerpiece of the strategy involving a challenging aza-Michael/intramolecular cyclization cascade reaction. A range of prochiral para-quinamines and α,ß-unsaturated aldehydes were investigated to afford 16 examples of hydroindoles possessing four contiguous stereocenters including one quaternary carbon. The hydroindole structures include multiple orthogonal functionalities, which underwent various transformations.

Solvent- and Catalyst-Free Synthesis of Nitrogen-Containing Bicycles through Hemiaminal Formation/Diastereoselective Hetero-Diels-Alder Reaction with Diazenes.

A solvent- and catalyst-free synthesis of nitrogen-containing bicyclic derivatives through a three-bond forming process is reported. Starting from dienals and readily available diazenes, the strategy involving the hemiaminal formation/hetero-Diels-Alder reaction affords the bicyclic products in a highly diastereoselective manner. This simple and green procedure has been applied to a selection of substrates, giving rise to 12 examples of nitrogen-containing bicyclic architectures. These products underwent various synthetic transformations. A sequence involving the cleavage of the hydrazine allowed the preparation of a hydantoin motif bearing an aminopropyl side chain, which is a structure found in natural products. A mechanism has also been suggested to explain the observed selectivities.

Merging oxidative dearomatization and aminocatalysis: one-pot enantioselective synthesis of tricyclic architectures.

The combination of oxidative dearomatization and trienamine/enamine activation in a single vessel is described. Under these conditions, a three-bond forming process generates functionalized tricyclic architectures with up to six contiguous stereocenters with excellent stereoselectivities from readily available planar substrates.