Hydrophobic Pockets of HPMC Enable Extremely Short Reaction Times in Water

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.