Redox Active N-Heterocyclic Carbenes in Oxidative NHC Catalysis.

An N-heterocyclic carbene (NHC) covalently linked to a quinone introduces a novel avenue for internal oxidations within oxidative NHC catalysis. The deployment of this hybrid NHC class promotes intramolecular electronic flow in the oxidation of the Breslow intermediate to acyl azolium. The use of the redox active NHC as a catalyst is facilitated by employing aerobic regeneration, yielding carboxylic esters with efficiencies of ≤99%, while generating water as the sole byproduct.

Regioselective ortho halogenation of N-aryl amides and ureas via oxidative halodeboronation: harnessing boron reactivity for efficient C-halogen bond installation.

The installation of the C-halogen bond at the ortho position of N-aryl amides and ureas represents a tool to prepare motifs that are ubiquitous in biologically active compounds. To construct such prevalent bonds, most methods require the use of precious metals and a multistep process. Here we report a novel protocol for the long-standing challenge of regioselective ortho halogenation of N-aryl amides and ureas using an oxidative halodeboronation. By harnessing the reactivity of boron over nitrogen, we merge carbonyl-directed borylation with consecutive halodeboronation, enabling the precise introduction of the C-X bond at the desired ortho position of N-aryl amides and ureas. This method offers an efficient, practical, and scalable solution for synthesizing halogenated N-heteroarenes under mild conditions, highlighting the superiority of boron reactivity in directing the regioselectivity of the reaction.

Photochemical Access to Substituted ß-Lactams and ß-Lactones via the Zimmerman-O'Connell-Griffin Rearrangement.

A photomediated protocol giving facile access to substituted ß-lactam and ß-lactones is presented. The method realizes, for the first time, the use of the Zimmerman-O'Connell-Griffin (ZOG) rearrangement in [2 + 2] cycloaddition. Products are obtained in high yield with excellent diastereoselectivity under visible light irradiation and under mild reaction conditions.

Aerobic Oxidative N-Heterocyclic Carbene Catalysis.

The ease with which simple starting materials can be transformed into highly functionalized products has made oxidative N-heterocyclic carbene (NHC) catalysis an area of significant interest. However, the use of stoichiometric amounts of high molecular weight oxidants in most reactions generates an undesired equivalent amount of waste. To address this issue, the use of oxygen as the terminal oxidant in NHC catalysis has been developed. Oxygen is attractive due to its low cost, low molecular weight, and ability to generate water as the sole by-product. However, molecular oxygen is challenging to use as a reagent in organic synthesis due to its unreactive ground state, which often requires reactions to be run at high temperatures and results in the formation of kinetic side-products. This review covers the development of aerobic oxidative carbene catalysis, including NHC-catalyzed reactions with oxygen, strategies for oxygen activation, and selectivity issues under aerobic conditions.

Overcoming Back Electron Transfer in the Electron Donor-Acceptor Complex-Mediated Visible Light-Driven Generation of α-Aminoalkyl Radicals from Secondary Anilines.

An additive-free, visible light-driven annulation between N-aryl amino acids and maleimide to form tetrahydroquinolines (THQs) is disclosed. Photochemical activation of an electron donor-acceptor (EDA) complex between amino acids and maleimides drives the reaction, and aerobic oxygen acts as the terminal oxidant in the net oxidative process. A range of N-aryl amino acids and maleimides have been investigated as substrates to furnish the target THQ in good to excellent yield. Mechanistic investigations, including titration and UV-vis studies, demonstrate the key role of the EDA complex as the photoactive species.

Boron-Mediated Regioselective Aromatic C-H Functionalization via an Aryl BF2 Complex.

An efficient regioselective functionalization of 2-aryl-heteroarenes and aryl aldehydes via an azaaryl BF2 complex has been developed. Mechanistically the reaction comprises fluoride to bromide ligand exchange on an aryl boron species and consecutive C-B bond cleavage to deliver a broad range of functionalized products. The reaction is high yielding, has a broad substrate scope where several different heteroarenes can be functionalized with chloro, bromo, iodo, hydroxyl, amine and BF2 in a highly regioselective fashion. The method can be applied for late-stage functionalization or for rapid skeleton remodeling with for instance cross-couplings.

Aerobic Oxidative N-Heterocyclic Carbene-Catalyzed Formal [3+3] Cyclization for the Synthesis of Tetrasubstituted Benzene Derivatives.

Herein, we present an accessible aerobic N-heterocyclic carbene (NHC)-catalyzed method that efficiently produces tetrasubstituted benzene rings in a single reaction. The method employs atmospheric oxygen (O2) as the terminal oxidant in a reaction that requires two oxidative steps. The aerobic oxidation is achieved by a selection of electron transfer mediators orchestrating a redox cascade, turning a high-energy aerobic oxidation reaction pathway into a favorable process.

Nanofluidic Trapping of Faceted Colloidal Nanocrystals for Parallel Single-Particle Catalysis.

Catalyst activity can depend distinctly on nanoparticle size and shape. Therefore, understanding the structure sensitivity of catalytic reactions is of fundamental and technical importance. Experiments with single-particle resolution, where ensemble-averaging is eliminated, are required to study it. Here, we implement the selective trapping of individual spherical, cubic, and octahedral colloidal Au nanocrystals in 100 parallel nanofluidic channels to determine their activity for fluorescein reduction by sodium borohydride using fluorescence microscopy. As the main result, we identify distinct structure sensitivity of the rate-limiting borohydride oxidation step originating from different edge site abundance on the three particle types, as confirmed by first-principles calculations. This advertises nanofluidic reactors for the study of structure-function correlations in catalysis and identifies nanoparticle shape as a key factor in borohydride-mediated catalytic reactions.

Aerobic Oxidative EDA Catalysis: Synthesis of Tetrahydroquinolines Using an Organocatalytic EDA Active Acceptor.

A catalytic electron donor-acceptor (EDA) complex for the visible-light-driven annulation reaction between activated alkenes and N,N-substituted dialkyl anilines is reported. The key photoactive complex is formed in situ between dialkylated anilines as donors and 1,2-dibenzoylethylene as a catalytic acceptor. The catalytic acceptor is regenerated by aerobic oxidation. Investigations into the mechanism are provided, revealing a rare example of a catalytic acceptor in photoactive EDA complexes that can give access to selective functionalization of aromatic amines under mild photochemical conditions.

Synthesis of cis-Oriented Vicinal Diphenylethylenes through a Lewis Acid-Promoted Annulation of Oxotriphenylhexanoates.

This study explores the synthesis of cyclic cis-vicinal phenyl ethylenes from oxotriphenylhexanoates. The reaction is a BBr3-promoted cyclization of 1,6-ketoesters (1) to five-membered diketo compounds (2). The synthesis is interesting as it constitutes one of the few examples of modular stereoselective synthesis of structures with a cis-oriented vicinal diphenylethylene. The core structure of 2 can be smoothly derivatized, which makes it a promising synthetic building block for further stereoselective synthetic applications.

Visible-Light-Driven Stereoselective Annulation of Alkyl Anilines and Dibenzoylethylenes via Electron Donor-Acceptor Complexes.

A catalyst-free, stereoselective visible-light-driven annulation reaction between alkenes and N,N-substituted dialkyl anilines for the synthesis of substituted tetrahydroquinolines is presented. The reaction is driven by the photoexcitation of an electron donor-acceptor (EDA) complex, and the resulting products are obtained in good to high yields with complete diastereoselectivity. Mechanistic rationale and photochemical characterization of the EDA-complex are provided.

Covalent incorporation of diphenylanthracene in oxotriphenylhexanoate organogels as a quasi-solid photon upconversion matrix.

Triplet-triplet annihilation photon upconversion (TTA-UC) in solid state assemblies are desirable since they can be easily incorporated into devices such as solar cells, thus utilizing more of the solar spectrum. Realizing this is, however, a significant challenge that must circumvent the need for molecular diffusion, poor exciton migration, and detrimental back energy transfer among other hurdles. Here, we show that the above-mentioned issues can be overcome using the versatile and easily synthesized oxotriphenylhexanoate (OTHO) gelator that allows covalent incorporation of chromophores (or other functional units) at well-defined positions. To study the self-assembly properties as well as its use as a TTA-UC platform, we combine the benchmark couple platinum octaethylporphyrin as a sensitizer and 9,10-diphenylanthracene (DPA) as an annihilator, where DPA is covalently linked to the OTHO gelator at different positions. We show that TTA-UC can be achieved in the chromophore-decorated gels and that the position of attachment affects the photophysical properties as well as triplet energy transfer and triplet-triplet annihilation. This study not only provides proof-of-principle for the covalent approach but also highlights the need for a detailed mechanistic insight into the photophysical processes underpinning solid state TTA-UC.

Polycyclizations of Ketoesters: Synthesis of Complex Tricycles with up to Five Stereogenic Centers from Available Starting Materials.

Here we present a polycyclization of oxotriphenylhexanoates. The polycyclization is governed by electronic effects, and three major synthetic paths have been established leading to stereochemically complex tricyclic frameworks with up to five stereogenic centers. The method is compatible with an array of functional groups, allowing pharmacophoric elements to be introduced post cyclization.

Multi-color emission with orthogonal input triggers from a diarylethene pyrene-OTHO organogelator cocktail.

We report on a pyrene-decorated supramolecular gelator based on an oxotriphenylhexanoate (OTHO) that can switch emission profiles between the solution and gel phase. A cocktail of the gelator and a photochromic diarylethene derivative enables four distinct emissive states to be obtained, which are modulated with light and heat as orthogonal input triggers.

An all-photonic full color RGB system based on molecular photoswitches.

On-command changes in the emission color of functional materials is a sought-after property in many contexts. Of particular interest are systems using light as the external trigger to induce the color changes. Here we report on a tri-component cocktail consisting of a fluorescent donor molecule and two photochromic acceptor molecules encapsulated in polymer micelles and we show that the color of the emitted fluorescence can be continuously changed from blue-to-green and from blue-to-red upon selective light-induced isomerization of the photochromic acceptors to the fluorescent forms. Interestingly, isomerization of both acceptors to different degrees allows for the generation of all emission colors within the red-green-blue (RGB) color system. The function relies on orthogonally controlled FRET reactions between the blue emitting donor and the green and red emitting acceptors, respectively.

A nanofluidic device for parallel single nanoparticle catalysis in solution.

Studying single catalyst nanoparticles, during reaction, eliminates averaging effects that are an inherent limitation of ensemble experiments. It enables establishing structure-function correlations beyond averaged properties by including particle-specific descriptors such as defects, chemical heterogeneity and microstructure. Driven by these prospects, several single particle catalysis concepts have been implemented. However, they all have limitations such as low throughput, or that they require very low reactant concentrations and/or reaction rates. In response, we present a nanofluidic device for highly parallelized single nanoparticle catalysis in solution, based on fluorescence microscopy. Our device enables parallel scrutiny of tens of single nanoparticles, each isolated inside its own nanofluidic channel, and at tunable reaction conditions, ranging from the fully mass transport limited regime to the surface reaction limited regime. In a wider perspective, our concept provides a versatile platform for highly parallelized single particle catalysis in solution and constitutes a promising application area for nanofluidics.

Writing and erasing multicolored information in diarylethene-based supramolecular gels.

A facile cocktail approach implying the mixing of diarylethene (DAE) photoswitches and low molecular weight gelators (LMWG) is presented. The photoresponsive gels exhibit multicolored emission that can be precisely controlled by different light exposure schemes (wavelength and dose), applicable for fluorescence patterning/writing. Including also a blue-emitting fluorophore allows for tri-chromatic color tuning of the emission via multistep energy transfer reactions, which in turn yields a non-linear response between the emission spectra and the light dose. This feature is highly desired in data security and anti-counterfeiting contexts. The information written in the gels can be conveniently erased by light, mass diffusion, or shaking; the latter being due to the thixotropic properties of the gels.

N-Acylation of Oxazolidinones via Aerobic Oxidative NHC Catalysis.

The first N-acylation of synthetically useful oxazolidinones with aldehydes using aerobic oxidative NHC catalysis is reported. The reaction offers a broad scope of functionalized oxazolidinones in good to excellent yields. Careful choice of electron transfer mediators proved pivotal to achieve efficient aerobic N-acylation, which has previously proven difficult using NHC catalysis. The methodology allows a mild entry to acylated oxazolidinones, avoiding the use of hazardous and reactive prefunctionalized substrates.

A Multi-Component Reaction towards the Development of Highly Modular Hydrogelators.

Herein we report a multi-component reaction approach for the development of a new class of hydrogelators based on the OxoTriphenylHexanOate (OTHO) backbone. A focused library of OTHOs has been synthesized and their hydrogelation features evaluated. The two most potent hydrogelators were studied by rheology revealing different stiffness, appearances and thixotropic behavior of the gels. The new gelators showcase the versatility of the OTHO backbone as a platform for the design of functionalized hydrogels with tunable gel properties.

α-Aminoalkyl Radical Addition to Maleimides via Electron Donor-Acceptor Complexes.

A catalyst-free, photochemical oxidative annulation reaction between dialkylanilines and maleimides to generate tetrahydroquinolines is presented. The reaction is driven by the photochemical activity of an electron donor-acceptor (EDA) complex and has a broad substrate scope with the corresponding products isolated in good to excellent yields. Photochemical characterization of the EDA complex and a mechanistic rational is provided.