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A convenient and versatile approach to important 1‐azaspirocyclic systems relevant to medicinal chemistry and natural products is reported herein. The main strategy relies on a reductive decarboxylative cyclization of redox‐active esters which can be rapidly assembled from abundant cyclic azaacids and tailored acceptor sidechains, with a focus on alkyne acceptors enabling the generation of useful exo‐alkene moieties. Diastereoconvergent variants were studied and could be achieved either through remote stereocontrol or conformational restriction in bicyclic carbamate substrates. Two sets of metal‐free photocatalytic conditions employing inexpensive eosin Y were disclosed and studied experimentally to highlight key mechanistic divergences. [ABSTRACT FROM AUTHOR]

Sulfones and carboxylic acids are prominent motifs widely present in the chemical structure of agrochemicals, pharmaceuticals and many other highly valuable compounds. Herein, we describe a conjunctive strategy for the precise installation of these functionalities onto styrenes using sodium sulfinates and CO2 as coupling partners. The protocol allowed the preparation of carboxy‐sulfonylated compounds in good yields and broad functional group tolerance. Additionally, taking advantage of the leaving group ability of the sulfone moiety, a one‐pot photocatalytic carboxy‐sulfonylation‐elimination strategy was developed for the synthesis of α‐aryl‐acrylates. [ABSTRACT FROM AUTHOR]

Tuning the redox potential of commonly available photocatalyst to improve the catalytic performance or expand its scope for challenging synthetic conversions is an ongoing demand in synthetic chemistry. Herein, the excited state properties and redox potential of commercially available [Ru(bpy)3]2+ photocatalyst were tuned by modifying the structure of the bipyridine ligands with electron‐donating/withdrawing units. The visible‐light‐mediated photoredox phosphorylation of tertiary aliphatic amines was demonstrated under mild conditions. A series of cross‐dehydrogenative coupling reactions were performed employing the RuII complexes as photocatalyst giving the corresponding α‐aminophosphinoxides and α‐aminophosphonates via carbon‐phosphorus (C−P) bond formation. [ABSTRACT FROM AUTHOR]

Light regulation of drug molecules has gained growing interest in biochemical and pharmacological research in recent years. In addition, a serious need for novel molecular targets of antibiotics has emerged presently. Herein, the development of a photocontrollable, azobenzene‐based antibiotic precursor towards tryptophan synthase (TS), an essential metabolic multienzyme complex in bacteria, is presented. The compound exhibited moderately strong inhibition of TS in its E configuration and five times lower inhibition strength in its Z configuration. A combination of biochemical, crystallographic, and computational analyses was used to characterize the inhibition mode of this compound. Remarkably, binding of the inhibitor to a hitherto‐unconsidered cavity results in an unproductive conformation of TS leading to noncompetitive inhibition of tryptophan production. In conclusion, we created a promising lead compound for combatting bacterial diseases, which targets an essential metabolic enzyme, and whose inhibition strength can be controlled with light. [ABSTRACT FROM AUTHOR]

Optogenetic and photopharmacological tools to manipulate neuronal inhibition have limited efficacy and reversibility. We report the design, synthesis, and biological evaluation of Fulgazepam, a fulgimide derivative of benzodiazepine that behaves as a pure potentiator of ionotropic γ‐aminobutyric acid receptors (GABAARs) and displays full and reversible photoswitching in vitro and in vivo. The compound enables high‐resolution studies of GABAergic neurotransmission, and phototherapies based on localized, acute, and reversible neuroinhibition. [ABSTRACT FROM AUTHOR]

Herein, a visible‐light photochemical approach for practical helicene functionalization at very mild reaction conditions is described. The photochemical reactions allow for the regiospecific and innate late‐stage functionalization of helicenes and are easily executed either through the activation of C(sp2)−Br bonds in helicenes using K2CO3 as inorganic base or direct C(sp2)−H helicene bond functionalization under oxidative photoredox reaction conditions. Overall, using these transformations six different functional groups are introduced to the helicene scaffold through C−C and four different C‐heteroatom bond‐forming reactions. [ABSTRACT FROM AUTHOR]

A photoinduced carboxylation of alkyl halides with CO2 at remote sp3 C−H sites enabled by the merger of photoredox and Ni catalysis is described. This protocol features a predictable reactivity and site selectivity that can be modulated by the ligand backbone. Preliminary studies reinforce a rationale based on a dynamic displacement of the catalyst throughout the alkyl side chain. [ABSTRACT FROM AUTHOR]

The first example for the photocatalytic generation of a highly electrophilic intermediate that is not based on radical reactivity is reported. The single‐electron reduction of bench‐stable and commercially available 4‐(trifluoromethoxy)benzonitrile by an organic photosensitizer leads to its fragmentation into fluorophosgene and benzonitrile. The in situ generated fluorophosgene was used for the preparation of carbonates, carbamates, and urea derivatives in moderate to excellent yields via an intramolecular cyclization reaction. Transient spectroscopic investigations suggest the formation of a catalyst charge‐transfer complex‐dimer as the catalytic active species. Fluorophosgene as a highly reactive intermediate, was indirectly detected via its next downstream carbonyl fluoride intermediate by NMR. Furthermore, detailed NMR analyses provided a comprehensive reaction mechanism including a water dependent off‐cycle equilibrium. Fluorophosgene was liberated by the photocatalytic reduction of a simple aryltrifluoromethoxyether. This highly reactive species was used for the synthesis of cyclic carbonates, carbamates and urea derivatives. The reaction mechanism was investigated by an in‐depth NMR study as well as cyclovoltammetry and transient spectroscopy which suggests a charge‐transfer complex dimer as the catalytic active species. [ABSTRACT FROM AUTHOR]

Artificial photosynthesis is one of the big scientific challenges of today. Self-assembled dynamic interfaces, such as vesicles or micelles, have been used as microreactors to mimic biological photosynthesis. These aggregates can help to overcome typical problems of homogeneous photocatalytic water splitting. Microheterogeneous environments organize catalyst-photosensitizer assemblies at the interface in close proximity and thus enhance intermolecular interactions. Thereby vesicles and micelles may promote photoinitiated charge separation and suppress back electron transfer. The dynamic self-assembled interfaces solubilize non-polar compounds and protect sensitive catalytic units and intermediates against degradation. In addition, vesicles provide compartmentation that was used to separate different redox environments needed for an overall water splitting system. This Minireview provides an overview of the applications of micellar and vesicular microheterogeneous systems for solar energy conversion by photosensitized water oxidation and hydrogen generation. [ABSTRACT FROM AUTHOR]

Functionalized vesicles for photocatalytic hydrogen production in water have been prepared by co-embedding of amphiphilic photosensitizers and a hydrogen-evolving catalyst in phospholipid membranes. The self-assembly allows a simple two-dimensional arrangement of the multicomponent system with close spatial proximity, which gave turnover numbers up to 165 for the incorporated amphiphilic cobaloxime water reduction catalyst 3 b under optimized conditions in purely aqueous solution. Superior photocatalytic activity in fluid membranes indicates that mobility and dynamic reorganization of catalytic subunits in the membrane promote the visible-light-driven hydrogen production. The functionalized membranes represent nanostructured assemblies for hydrogen production in aqueous solution mimicking natural photosynthesis. [ABSTRACT FROM AUTHOR]

A series of 10-arylflavins (10-phenyl-, 10-(2′,6′-dimethylphenyl)-, 10-(2′,6′-diethylphenyl)-, 10-(2′,6′-diisopropylphenyl)-, 10-(2′- tert-butylphenyl)-, and 10-(2′,6′-dimethylphenyl)-3-methylisoalloxazine ( 2 a- f)) was prepared as potentially nonaggregating flavin photocatalysts. The investigation of their structures in the crystalline phase combined with 1H-DOSY NMR spectroscopic experiments in CD3CN, CD3CN/D2O (1:1), and D2O confirm the decreased ability of 10-arylflavins 2 to form aggregates relative to tetra- O-acetyl riboflavin ( 1). 10-Arylflavins 2 a- d do not interact by π-π interactions, which are restricted by the 10-phenyl ring oriented perpendicularly to the isoalloxazine skeleton. On the other hand, N3H⋅⋅⋅O hydrogen bonds were detected in their crystal structures. In the structure of 10-aryl-3-methylflavin ( 2 f) with a substituted N3 position, weak CH⋅⋅⋅O bonds and weak π-π interactions were found. 10-Arylflavins 2 were tested as photoredox catalysts for the aerial oxidation of 4-methoxybenzyl alcohol to the corresponding aldehyde (model reaction), thus showing higher efficiency relative to 1. The quantum yields of 4-methoxybenzyl alcohol oxidation reactions mediated by arylflavins 2 were higher by almost one order of magnitude relative to values in the presence of 1. [ABSTRACT FROM AUTHOR]

Biological membranes play a key role for the function of living organisms. Thus, many artificial systems have been designed to mimic natural cell membranes and their functions. A useful concept for the preparation of functional membranes is the embedding of synthetic amphiphiles into vesicular bilayers. The dynamic nature of such noncovalent assemblies allows the rapid and simple development of bio-inspired responsive nanomaterials, which find applications in molecular recognition, sensing or catalysis. However, the complexity that can be achieved in artificial functionalized membranes is still rather limited and the control of their dynamic properties and the analysis of membrane structures down to the molecular level remain challenging. [ABSTRACT FROM AUTHOR]