Photocatalytic Decarboxylative Fluorination by Quinone-Based Isoreticular Covalent Organic Frameworks

Abstract

The strategic incorporation of fluorine atoms into molecules has become a cornerstone of modern pharmaceuticals, agrochemicals, and materials science. Herein, we have developed a covalent organic framework (COF)-based, robust photocatalyst that enables the photofluorodecarboxylation reaction of diverse carboxylic acids, producing alkyl fluorides with remarkable efficiency. The catalytic activity of an anthraquinone-based COF catalyst TpAQ outperforms other structurally analogous β-ketoenamine COFs. Through comprehensive control experiments, photoluminescence, and electrochemical studies, we have elucidated the unique features of the material and the mechanistic pathway. This in-depth understanding has paved the way for optimizing the reaction conditions and achieving high yields of alkyl fluorides. The versatility of this protocol extends to a broad range of aliphatic acids with diverse functional groups and heterocycles. It also enabled the late-stage diversification of anti-inflammatory drugs and steroid derivatives. This opens up exciting possibilities for synthesizing novel pharmaceuticals and functionalized molecules. The methodology was also generalized to other light-mediated decarboxylative halogenation reactions. Furthermore, our method demonstrates scalability under both batch and continuous flow conditions, offering a promising approach for large-scale production. Additionally, the TpAQ catalyst exhibits exceptional durability and can be reused multiple times without significant activity loss (>80% yield after the eighth cycle), making it a sustainable and cost-effective solution. This work lays the foundation for developing efficient and sustainable light-driven synthesis methods using COFs as photocatalysts with potential applications beyond alkyl halide synthesis.