Following the successful construction of the hindered and polyfluorinated dialkyl ethers, we aimed to validate the practicality of this method. To achieve this, we successfully incorporated the challenging ether motifs into drugs and natural products, such as sertraline, flavanones, cetirizine, salicylic acid, and ketoprofen (Figure , 104d-112d), obtaining satisfactory yields ranging from 36% to 91% within 16 h of reaction time. Given the prevalence of tertiary alcohols in nature, we applied a range of naturally occurring tertiary alcohols, including lercanidipine sidechain, α-terpineol, cedrol, stiripentol, D-menthol, cholesterol, diacetonefructose, and geraniol, in the synthesis of the hindered and polyfluorinated ethers (113d-122d). This indicated the robustness of our strategy for synthesizing challenging ethers. To further demonstrate the practical application of this strategy in drug discovery, we conducted a rapid and modular derivatization of the marketed drug fenofibrate, resulting in 13 drug analogues with challenging ether groups (Figure ). Fenofibrate has been widely used to reduce triglycerides, uric acid levels, and treat type 2 diabetes and metabolic syndrome. Importantly, the repurposing marketed drugs and their derivatives can be a prevalent strategy in drug development because of their safety, costeffectiveness, and shorter R&D cycles. Our approach proposed a convenient method for quickly modifying carbonyl functional group-based drugs, facilitating the discovery of new therapeutic applications for fenofibrate. Additionally, we efficiently synthesized another important marketed drug, the dopamine reuptake inhibitor, vanoxerine, using this sustainable strategy. The key intermediate (136d