Reagent and Catalyst Capsules: A Chemical Delivery System for Reaction Screening and Parallel Synthesis

Abstract

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.

Organic synthesis in Aqueous Multiphase Systems — Challenges and opportunities ahead of us

“…More recently, water chemistry enabled by polymers has led to several remarkable advances [9,10,56,57] with researchers at Abbvie, led by Braje, who, in partnering with Handa, demonstrated spectacular rate enhancements during reactions performed in water. The key additive is the readily available and biodegradable polymer HPMC.…”

HPMC: A Biomass-Based Semisynthetic Sustainable Additive Enabling Clean and Fast Chemistry in Water

“…49−51 Along these lines, AbbVie has recently reported the use of inexpensive HPMC shells filled with catalyst and base, as reagent capsules for C−N and C−C cross-couplings. 32 HPMC capsules are cheap, readily available, and compatible with hygroscopic reagents, and they offer good protection of the catalyst and ligands from oxygen and water. 52 It has been reported elsewhere that HPMC capsules display protection against oxygen transmission (166 cm 3 /(m 2 day)), their water vapor transmission rate is 263 g/(m 2 day).…”

Teflon Magnetic Stirring Capsules (TMSC) as a Practical and Reusable Delivery System for Sensitive Reagents and Catalysts

“…For these reactions [Ni(cod) 2 ] ( 1 ), a notoriously sensitive Ni(0) precatalyst, was wax‐encapsulated [15–17] . Other vehicles have been developed such as paraffin‐sealed glass shells or, [18] more recently, hydroxypropyl methylcellulose capsules (HPMC) [19] . The latter provide the distinct advantages to be available in various sizes and to generate less waste than their paraffin‐based counterparts.…”