Although greener and faster access to fine chemicals and APIs is highly desirable, there are currently no synthetic methodologies which undergo reaction completions within a few seconds to minutes in water under benchtop laboratory conditions. Here, we report a methodology that allows the instantaneous formation of ligated ultrasmall Pd nanoparticles in the hydrophobic pockets of benign cellulose derivative (HPMC) for chemical reactions to proceed very fast in water under mild reaction conditions. Unprecedented short reaction times were exemplified for the Buchwald–Hartwig aminations. In addition, very short reaction times of less than a minute were also demonstrated for the amide couplings, which is the most utilized reaction type in the pharmaceutical industry.

Commercially available hydroxypropyl methylcellulose capsules are employed as a fast, safe, and user-friendly chemical delivery system containing all reagents (catalyst, ligand, and base) for three important transition-metal-catalyzed reactions: Buchwald–Hartwig, Suzuki–Miyaura, and metallophotoredox C–N cross-coupling reactions. This encapsulation methodology simplifies the screening of reaction conditions and the preparation of compound libraries using parallel synthesis in organic solvents or aqueous media. These reagents-containing HPMC capsules are easy to prepare, come in different sizes, and can be stored on the bench under noninert conditions.

Compressed tablets containing a mixture of a photocatalyst, a nickel catalyst, an inorganic base, and an inert excipient are employed as a fast, safe, and user-friendly chemical delivery system for two different metallophotoredox-catalyzed reactions. This delivery method simplifies the preparation of compound libraries using photoredox chemistry in a parallel setting. The reagent tablets were successfully applied to late-stage functionalization of drug-like intermediates. These tablets can be prepared with various reagents and catalysts in different sizes and be stored on the bench thanks to blister packaging.