In the micelle of PS-750-M, the presence of 3° amides from the surfactant proline linker mimics dimethylformamide, dimethylacetamide, and N-methyl-2-pyrrolidone. The resultant micellar properties enable extremely fast amide couplings mediated by 1-ethyl-3-(3-(dimethylamino)­propyl)­carbodiimide (without hydroxybenzotriazole), rather than expensive and specialized coupling agents. Conditions have been developed wherein products precipitate, and isolation by filtration completely avoids the use of organic solvent. This methodology is scalable and avoids product epimerization.

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.

In the forebrain, synaptic glycine concentrations are regulated through the glycine transporter GlyT1. Because glycine is a coagonist of the N-methyl-D-aspartate (NMDA) receptor (NMDAR), which has been implicated in schizophrenia, inhibition of GlyT1 is thought to provide an option for the treatment of schizophrenia.

Scheme2.Heck-Mizorokir eaction in g-valerolactone.Scheme3.Synthesis of 1-butyl-3-methylimidazoliumchloride using scCO 2 .Scheme1.Suzuki-Miyaura coupling in 2-Me-THF.Scheme4.Improved synthetic route to sildenafilc itrate.Scheme5.Improved synthetic route to ibuprofen.Scheme6.Cu-catalyzed cyclopropanation.Scheme17. Amination in synthesis of efaproxiral.Scheme15. Peptide couplingsint he synthesis of sildenafil and sunitinib.Scheme16. Amide couplings in water.Scheme20. Couplings of unactivated (iso)quinolines in PS-750-M.Scheme21. PS-750-M as ar eplacement for toxic polar-aprotic solvent for sp 2 -sp 3 couplings.Scheme22. Recyclable palladium nanoparticles in PS-750-M for olefins ynthesis through carbene insertion.Scheme23. Drugmolecules containingC ÀNb onds.Scheme24. Recyclable bimetallic nanoparticles for sustainable Buchwald-Hartwig aminations in water.Scheme25. Ac omparison between chemistryinw ater versus chemistryino rganic solvents (Novartis Pharmaceuticals).

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.