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The importance of constructing Csp2-Csp3 bonds has motivated the development of electrochemical, photochemical and thermal activation methods to reductively couple abundant aryl and alkyl electrophiles. However, these methodologies are limited to couplings of very specific substrate classes and require specialized sets of catalysts and reaction set-ups. Here we show a consolidation of these myriad strategies into a single set of conditions that enable reliable alkyl-aryl couplings, including those that were previously unknown. These reactions rely on the discovery of unusually persistent organonickel complexes that serve as stoichiometric platforms for C(sp2)-C(sp3) coupling. Aryl, heteroaryl or vinyl complexes of Ni can be inexpensively prepared on a multigram scale by mild electroreduction from the corresponding C(sp2) electrophile. Organonickel complexes can be isolated and stored or telescoped directly to reliably diversify drug-like molecules. Finally, the procedure was miniaturized to micromole scales by integrating soluble battery chemistries as redox initiators, enabling a high-throughput exploration of substrate diversity.
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INTRODUCTION: Pulmonary artery thrombosis presents a rare and formidable challenge, especially in individuals with untreated complex congenital heart diseases and concurrent valvular abnormalities. PRESENTATION OF CASE: This case details a distinctive instance of pulmonary artery thrombosis in a patient with untreated congenital atrial septal defect, severe pulmonary hypertension, pulmonary aneurysm, valvular heart disease, and triple-positive antiphospholipid antibodies. Collaborative decision-making by a heart team guided the diagnostic and therapeutic processes, resulting in surgical interventions encompassing pulmonary thrombectomy, mitral and tricuspid regurgitation repair, and atrial septal defect closure. DISCUSSION: The case underscores the nuanced management of pulmonary artery thrombosis within the realm of congenital heart disease, highlighting the imperative role of a multidisciplinary approach in achieving accurate diagnoses and timely interventions. The multifaceted treatment strategy implemented further accentuates the need for continual monitoring and personalized interventions in intricate clinical scenarios. CONCLUSION: In conclusion, this case emphasizes the complexity of addressing pulmonary artery thrombosis in the context of congenital heart disease. The collaborative efforts of a multidisciplinary team proved pivotal in navigating diagnostic uncertainties and formulating a tailored treatment plan. Ongoing monitoring and personalized strategies remain crucial for optimizing outcomes in such intricate cases.
RESUMO
An electrochemical, nickel-catalyzed reductive coupling of alkylpyridinium salts and aryl halides is reported. High-throughput experimentation (HTE) was employed for rapid reaction optimization and evaluation of a broad scope of pharmaceutically relevant structurally diverse aryl halides, including complex drug-like substrates. In addition, the transformation is compatible with both primary and secondary alkylpyridinium salts with distinct conditions. Mechanistic insights were critical to enhance the efficiency of coupling using secondary alkylpyridinium salts. Systematic comparisons of the electrochemical and non-electrochemical methods revealed the complementary scope and efficiency of the two approaches.