Metal‐ and Reagent‐Free Dehydrogenative Formal Benzyl–Aryl Cross‐Coupling by Anodic Activation in 1,1,1,3,3,3‐Hexafluoropropan‐2‐ol

A selective dehydrogenative electrochemical functionalization of benzylic positions that employs 1,1,1,3,3,3‐hexafluoropropan‐2‐ol (HFIP) has been developed. The electrogenerated products are versatile intermediates for subsequent functionalizations as they act as masked benzylic cations that can be easily activated. Herein, we report a sustainable, scalable, and reagent‐ and metal‐free dehydrogenative formal benzyl–aryl cross‐coupling. Liberation of the benzylic cation was accomplished through the use of acid. Valuable diarylmethanes are accessible in the presence of aromatic nucleophiles. The direct application of electricity enables a safe and environmentally benign chemical transformation as oxidizers are replaced by electrons. A broad variety of different substrates and nucleophiles can be employed.     

Electrocatalytic Recycling of CO2 and Small Organic Molecules

As global warming directly affects the ecosystems and humankind in the 21^st century, attention and efforts are continuously being made to reduce the emission of greenhouse gases, especially carbon dioxide (CO₂). In addition, there have been numerous efforts to electrochemically convert CO₂ gas to small organic molecules (SOMs) and vice versa. Herein, we highlight recent advances made in the electrocatalytic recycling of CO₂ and SOMs including (i) the overall trend of research activities made in this area, (ii) the relations between reduction conditions and products in the aqueous phase, (iii) the challenges in the use of gas diffusion electrodes for the continuous gas phase CO₂ reduction, as well as (iv) the development of state of the art hybrid techniques for industrial applications. Perspectives geared to fully exploit the potential of zero‐gap cells for CO₂ reduction in the gaseous phase and the high applicability on a large scale are also presented. We envision that the hybrid system for CO₂ reduction supported by sustainable solar, wind, and geothermal energies and waste heat will provide a long term reduction of greenhouse gas emissions and will allow for continued use of the abundant fossil fuels by industries and/or power plants but with zero emissions.     

A Supramolecular Complex in Small-Molecule Solar Cells based on Contorted Aromatic Molecules

"Ball and socket" motif: The contorted dibenzotetrathienocoronene (6-DBTTC) forms a complex with the C(70) fullerene PC(70) BM embedded in an amorphous phase of PC(70) BM. The materials are processable into organic solar cells in solution. The power conversion efficiency is maximal when there is a 1:2 molar ratio of 6-DBTTC to PC(70) BM. Formation of the supramolecular complex directly affects charge separation in the active layer.     

Asymmetric Total Synthesis of the Complex Polycyclic Xanthone FD‐594

A highly convergent approach was developed to achieve the first asymmetric and scalable total synthesis of FD‐594, a complex polycyclic xanthone natural product from Streptomyces sp. TA‐0256, in a longest linear sequence (LLS) of 20 steps. The trans‐9,10‐dihydrophenanthrene‐9,10‐diol fragment (B‐C‐D ring) was generated through a new strategy involving asymmetric dihydroxylation followed by Cu‐mediated oxidative cyclization. Late‐stage stereoselective glycosylation assembled the angular hexacyclic framework with a β‐linked 2,6‐dideoxy trisaccharide fragment.     

Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody–drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products.     

Natural Products Originated from the Oxidative Coupling of Tyrosine and Tryptophan: Biosynthesis and Bioinspired Synthesis

The oxidative coupling of tyrosine and tryptophan units is a pivotal step in the total synthesis of some peptide-derived marine and terrestrial natural products, such as the diazonamides, azonazine and tryptorubin A. This Minireview details the biosynthesis and bioinspired synthesis of natural products with such structures. A special focus is put on the challenges of the synthesis of these natural products and the innovative solutions adopted by synthetic chemists.     

CO2 Methanation via Amino Alcohol Relay Molecules Employing a Ruthenium Nanoparticle/Metal Organic Framework Catalyst

Methanation of carbon dioxide (CO₂) is attractive within the context of a renewable energy refinery. Herein, we report an indirect methanation method that harnesses amino alcohols as relay molecules in combination with a catalyst comprising ruthenium nanoparticles (NPs) immobilized on a Lewis acidic and robust metal–organic framework (MOF). The Ru NPs are well dispersed on the surface of the MOF crystals and have a narrow size distribution. The catalyst efficiently transforms amino alcohols to oxazolidinones (upon reaction with CO₂) and then to methane (upon reaction with hydrogen), simultaneously regenerating the amino alcohol relay molecule. This protocol provides a sustainable, indirect way for CO₂ methanation as the process can be repeated multiple times.     

The Biocatalytic Repertoire of Natural Biaryl Formation

The catalytic and selective construction of carbon–carbon bonds for the generation of complex molecules is one of the most important tasks in organic chemistry. This was clearly highlighted by the 2010 Nobel Prize in Chemistry, which was awarded for the development of Pd‐catalyzed cross‐coupling reactions. The underlying concept of cross‐linking building blocks to generate molecular complexity can also be widely found in natural product biosynthesis. Impressive examples for such natural cross‐coupling reactions are biosynthetic processes for the assembly of biaryl moieties in natural products—highly efficient enzymatic reactions that often achieve synthetically yet unmatched selectivities. This Minireview highlights selected examples that showcase these fascinating biotransformations.     

Active Molybdenum‐Based Anode for Dehydrogenative Coupling Reactions

A new and powerful active anode system that can be operated in 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) has been discovered. In HFIP the molybdenum anode forms a compact, conductive, and electroactive layer of higher‐valent molybdenum species. This system can replace powerful but stoichiometrically required Mo^V reagents for the dehydrogenative coupling of aryls. This electrolytic reaction is more sustainable and allows the conversion of a broad scope of activated arenes.     

Developments in the Dehydrogenative Electrochemical Synthesis of 3,3′,5,5′-Tetramethyl-2,2′-biphenol

The symmetric biphenol 3,3′,5,5′-tetramethyl-2,2′-biphenol is a well-known ligand building block and is used in transition-metal catalysis. In the literature, there are several synthetic routes for the preparation of this exceptional molecule. Herein, the focus is on the sustainable electrochemical synthesis of 3,3′,5,5′-tetramethyl-2,2′-biphenol. A brief overview of the developmental history of this inconspicuous molecule, which is of great interest for technical applications, but has many challenges for its synthesis, is provided. The electro-organic method is a powerful, sustainable, and efficient alternative to conventional synthesis to obtain this symmetric biphenol up to the kilogram scale. Another section of this article is devoted to different process management strategies in batch-type and flow electrolysis and their respective advantages.