Merging [2+2] Cycloaddition with Radical 1,4‐Addition: Metal‐Free Access to Functionalized Cyclobuta[a]naphthalen‐4‐ols

A metal‐free [2+2] cycloaddition and 1,4‐addition sequence induced by S‐centered radicals has been achieved by treating benzene‐linked allene‐ynes with aryldiazonium tetrafluoroborates and DABCO‐bis(sulfur dioxide) in a one‐pot procedure. The reaction provides a greener and more practical access to functionalized cyclobuta[a]naphthalen‐4‐ols with valuable applications. More than 50 examples are demonstrated with excellent diastereoselectivity and chemical yields. The reaction pathway is proposed to proceed by the following steps:[2+2] cycloaddition, insertion of SO₂, 1,4‐addition, diazotization, and tautomerization.     

Automated Synthesis of Well‐Defined Polymers and Biohybrids by Atom Transfer Radical Polymerization Using a DNA Synthesizer

A DNA synthesizer was successfully employed for preparation of well‐defined polymers by atom transfer radical polymerization (ATRP), in a technique termed AutoATRP. This method provides well‐defined homopolymers, diblock copolymers, and biohybrids under automated photomediated ATRP conditions. PhotoATRP was selected over other ATRP methods because of mild reaction conditions, ambient temperature, tolerance to oxygen, and no need to introduce reducing agents or radical initiators. Both acrylate and methacrylate monomers were successfully polymerized with excellent control in the DNA synthesizer. Diblock copolymers were synthesized with different targeted degrees of polymerization and with high retention of chain‐end functionality. Both hydrophobic and hydrophilic monomers were grafted from DNA. The DNA‐polymer hybrids were characterized by SEC and DLS. The AutoATRP method provides an efficient route to prepare a range of different polymeric materials, especially polymer‐biohybrids.     

Precision PEGylated Polymers Obtained by Sequence‐Controlled Copolymerization and Postpolymerization Modification

Copolymers containing water‐soluble poly(ethylene glycol) (PEG) side chains and precisely controlled functional microstructures were synthesized by sequence‐controlled copolymerization of donor and acceptor comonomers, that is, styrene derivatives and N‐substituted maleimides. Two routes were compared for the preparation of these structures: a) the direct use of a PEG–styrene macromonomer as a donor comonomer, and b) the use of an alkyne‐functionalized styrenic comonomer, which was PEGylated by copper‐catalyzed alkyne–azide cycloaddition after polymerization. The latter method was found to be the most versatile and enabled the synthesis of high‐precision copolymers. For example, PEGylated copolymers containing precisely positioned fluorescent (e.g. pyrene), switchable (e.g. azobenzene), and reactive functionalities (e.g. an activated ester) were prepared.     

Sequence‐Controlled Polymers via Simultaneous Living Anionic Copolymerization of Competing Monomers

Natural macromolecules, i.e., sequence‐controlled polymers, build the basis for life. In synthetic macromolecular chemistry, reliable tools for the formation of sequence‐controlled macromolecules are rare. A robust and efficient chain‐growth approach based on the simultaneous living anionic polymerization of sulfonamide‐activated aziridines for sequence control of up to five competing monomers resulting in gradient copolymers is presented. The simultaneous azaanionic copolymerization is monitored by real‐time ¹H NMR spectroscopy for each monomer at any time during the reaction. The monomer sequence can be adjusted by the monomer reactivity, depending on the electron‐withdrawing effect by the sulfonamide (nosyl‐, brosyl‐, tosyl‐, mesyl‐, busyl) groups. This method offers unique opportunities for sequence control by competing copolymerization: a step forward to well‐engineered synthetic polymers with defined microstructures.

     

Iminyl‐Radicals by Oxidation of α‐Imino‐oxy Acids: Photoredox‐Neutral Alkene Carboimination for the Synthesis of Pyrrolines

The visible‐light‐promoted decarboxylation of α‐imino‐oxy propionic acids for the generation of iminyl radicals has been accomplished through the use of Ir(dFCF₃ppy)₂(dtbbpy)PF₆ as a photoredox catalyst. Different from visible‐light‐promoted homolysis and single‐electron reduction of oxime derivatives, this strategy provides a novel catalytic cycle for alkene carboimination through a sequence comprising N‐radical generation, iminyl radical cyclization, intermolecular conjugate addition to a Michael acceptor, and single‐electron reduction to afford various pyrroline derivatives in an overall redox‐neutral process. The indolizidine alkaloid skeleton could be easily constructed from a pyrroline derivative prepared by this synthetic method.     

Metal‐Free,Room‐Temperature,Radical Alkoxycarbonylation of Aryldiazonium Salts through Visible‐Light Photoredox Catalysis

The first radical alkoxycarboxylation of aryldiazonium salts using CO gas through visible‐light‐induced photoredox catalysis (16 W blue LEDs) has been developed. This reaction is entirely metal‐free, is carried out at room temperature with a low loading of an organic dye as a photocatalyst (0.5 mol %), and provides a wide range of arylcarboxylic acid esters in high yields. Importantly, this photocatalytic system can be successfully extended to other carboxylation reactions.     

Photoredox‐Catalyzed Site‐Selective α‐C(sp3)−H Alkylation of Primary Amine Derivatives

The synthetic utility of tertiary amines to oxidatively generate α‐amino radicals is well established, however, primary amines remain challenging because of competitive side reactions. This report describes the site‐selective α‐functionalization of primary amine derivatives through the generation of α‐amino radical intermediates. Employing visible‐light photoredox catalysis, primary sulfonamides are coupled with electron‐deficient alkenes to efficiently and mildly construct C?C bonds. Interestingly, a divergence between intermolecular hydrogen‐atom transfer (HAT) catalysis and intramolecular [1,5] HAT was observed through precise manipulation of the protecting group. This dichotomy was leveraged to achieve excellent α/δ site‐selectivity.     

Synthesis of Tri‐ and Difluoromethoxylated Compounds by Visible‐Light Photoredox Catalysis

Trifluoromethoxy (OCF₃) and difluoromethoxy (OCF₂H) groups are fluorinated structural motifs that exhibit unique physicochemical characteristics. Incorporation of these substituents into organic molecules is a highly desirable approach used in medicinal chemistry and drug discovery processes to alter the properties of a parent compound. Recently, tri‐ and difluoromethyl ethers have received increasing attention and several innovative strategies to access these valuable functional groups have been developed. The focus of this Minireview is the use of visible‐light photoredox catalysis in the synthesis of tri‐ and difluoromethyl ethers. Recent photocatalytic strategies for the formation of O?CF₃, C?OCF_3, O?CF₂H, and C?OCF₂H bonds as well as other transformations leading to the construction of OR_F groups are discussed herein.     

Super‐heptazethrene

The challenging synthesis of a laterally extended heptazethrene molecule, the super‐heptazethrene derivative SHZ‐CF3 , is reported. This molecule was prepared using a strategy involving a multiple selective intramolecular Friedel–Crafts alkylation followed by oxidative dehydrogenation. Compound SHZ‐CF3 exhibits an open‐shell singlet diradical ground state with a much larger diradical character compared with the heptazethrene derivatives. An intermediate dibenzo‐terrylene SHZ‐2H was also obtained during the synthesis. This study provides a new synthetic method to access large‐size quinoidal polycyclic hydrocarbons with unique physical properties.