Aromatic ring-opening metathesis and development of novel photoredox- and transition metal-catalyzed (atroposelective) synthetic methods

Isoacridone Dyes with Parallel Reactivity from Both Singlet and Triplet Excited States for Biphotonic Catalysis and Upconversion
Over the past decades, photoredox catalysis has earned prominent recognition as an invaluable tool for generating radical intermediates under mild reaction conditions and enabling transformations that would otherwise be inaccessible via traditional methodologies. A substantial part of the developed photoredox-catalyzed reactions, especially at the outset, rely on the utilization of polypyridyl transition metal complexes, such as ruthenium and iridium catalysts. While metal-based photosensitizers are known for quantitative intersystem crossing into photoactive triplet excited states, organic photosensitizers, on the other hand, are often characterized by weak spin-orbit coupling and low intersystem crossing efficiencies, thereby leading to photoactive singlet excited states. Considering that newly emerging biphotonic reactions addressing particularly challenging transformations typically involve a triplet-triplet energy transfer step, the development of new types of organic sensitizers suitable for these applications arises as an important objective. Thus, we designed a new family of organic photocatalysts, the isoacridones, in which singlet- and triplet-excited states are simultaneously photoactive. These new isoacridone dyes are synthetically readily accessible by our three-step method, consisting of aryne-imine-aryne coupling, oxidation of the obtained acridane, followed by nucleophilic aromatic substitution of one fluorine atom, and demonstrate intersystem crossing efficiencies of up to 52%, forming microsecond-lived triplet excited states (T1) and storing approximately 1.9 eV of energy. Conversely, their photoactive singlet excited states (S1) populated in parallel are described by only nanosecond lifetimes, but store ∼0.4 eV more energy and perform as strong oxidants. Owing to these favorable features, the new isoacridone photosensitizers are suitable for applications requiring parallel triplet–triplet energy transfer and photoinduced electron transfer elementary steps. This hypothesis was affirmed by successful implementation of the prepared isoacridones for Birch-type arene reductions and C–C couplings via sensitization-initiated electron transfer. These examples illustrate the strong potential of this photocatalysts family to serve as a more sustainable replacement for iridium- or ruthenium-based photocatalysts. Furthermore, in combination with a pyrene-based annihilator, sensitized triplet–triplet annihilation upconversion was achieved in an all-organic system, where the upconversion quantum yield correlated with the intersystem crossing quantum yield of the photosensitizer.
Decarboxylative Nickel- and Photoredox-Catalyzed Aminocarbonylation of (Hetero)Aryl Bromides
The amide bond is an exceptionally important structural motif, serving not only as the backbone of peptides but also as the linkage in numerous small bioactive pharmaceuticals and agrochemicals. Although numerous new protocols for amidation – one of the most frequently performed reactions – were developed over the last years, many still suffer from inherent limitations, the need for stoichiometric reagents, poor atom economy, and safety concerns. One of the approaches to amide synthesis relies on the initial formation of the desired N–C(C=O) bond, followed by the installation of the adjacent C–C bond with the required substituents. This strategy could be realized by the generation of carbamoyl radicals as reactive intermediates. We hence optimized and explored the scope of nickel- and organophotoredox-catalyzed aminocarbonylation of aryl halides, employing oxamic acids as readily available carbamoyl radical precursors, with CO2 as the only byproduct. The optimized methodology proved to be highly efficient for oxamic acids bearing halides and electron-donating groups, whereas electron-deficient (hetero)aryl bromides were suitable coupling partners in this reaction. Furthermore, substrates bearing sterically hindered adamantlyl or isopropyl groups successfully underwent the desired transformation under the optimized reaction conditions, further demonstrating the robustness of the methodology. To support the proposed mechanism and generation of carbamoyl radical in particular, we also explored the preparation of deuterated formamides by synergistic thiol and photoredox catalysis utilizing D2O as an inexpensive deuterium source. Inspired by this deuteration protocol, we showed the feasibility of the synthesis of deuterated bicyclo[1.1.1]pentanes via the carbamoyl radical-promoted ring-opening of [1.1.1]propellane, followed by the deuterium atom transfer.
Control over Stereogenic N–N Axes by Pd-catalyzed 5-endo-Hydroaminocyclization
Atropisomeric compounds – stereoisomers arising from the restricted rotation about a single bond – have become of significant interest in recent years due to their vast potential for applications in a variety of fields, including drug discovery, catalysis, and molecular nanoscience. Substituted biaryls possessing C–C stereogenic axes are among the most intensively investigated classes of atropisomers and are represented by a variety of broadly utilized ligands in stereoselective catalysis. Additionally, numerous catalyst-controlled stereoselective methods to forge N–C atropisomers have recently emerged. In contrast to the well-explored C–C and N–C atropisomers, scaffolds bearing N–N stereogenic axes have remained overlooked and underdeveloped until recently, when the first reports on their stereoselective synthesis appeared. Despite these seminal reports, efficient procedures to prepare N–N stereogenic compounds are still scarce, as evidenced by rare examples of indole-carbazole derivatives obtained only with low enantioselectivities, for instance. Therefore, we developed a novel approach for the stereoselective construction of N–N atropisomeric compounds by a Pd-catalyzed 5-endo-hydroaminocyclization. A broad range of bisheterocycles, connected by a configurationally stable N–N stereogenic axis, were prepared with catalyst control in enantioenriched form with up to 87:13 atroposelectivity and 90% yield.
Aromatic Ring-Opening Metathesis
Aromatic compounds are extensively utilized in organic synthesis due to their unique properties, including characteristic interactions, defined molecular shape and, most notably, a wide array of methods available for their synthesis and further functionalizations. Contrarily, the transformations involving cleavage of inert aromatic carbon-carbon bonds remain underdeveloped due to the unfavourable energetics of aromaticity disruption. Having gained significant recognition, particularly marked by a Nobel Prize, alkene metathesis has become an indispensable tool for versatile carbon-carbon bond-forming and breaking reactions for non-aromatic structures. Nonetheless, despite remarkable field`s advancements, strategies to open aromatic compounds by metathesis remained elusive, which was further supported by DFT studies revealing benzene ring as unsuitable substrate for metathesis. To address the prevailing bias that aromatic ring-opening metathesis is unattainable transformation and to reveal its extensive potential, we disclose the feasibility of aromatic ring-opening metathesis (ArROM) to cleave a diversity of aromatic rings, including tetraphene, naphthalene, indole, benzofuran and phenanthrenes by employing Schrock-Hoveyda molybdenum alkylidene catalysts. The power of the developed method was illustrated by its application to the bidirectional synthesis of extended polycyclic aromatic hydrocarbons by twofold ArROM – twofold RCM cascades. Moreover, stereoselective aromatic ring-opening metathesis with exquisite catalyst control over the configuration of C–C and C–N atropisomers was accomplished with chiral Schrock-Hoveyda molybdenum alkylidene catalysts. Additionally, the performed DFT calculations were utilized to rationalize the differences in behavior of various catalytic systems, uncovering smaller values of energy barriers for Mo-based complexes in comparison to Ru-based catalysts. Aromatic ring-opening metathesis is therefore a viable and efficient approach to catalytically transform and interconvert various aromatics without the requirement for any reagents or photoexcitation.