The breaking beads approach for photocleavage from solid support

Photochemical transformations are one of the most interesting yet challenging synthetic approaches. Reactions using light does not require toxic or dangerous reagents and can be very selective. Photo-labile moieties are attractive alternative to standard protecting groups because they can be removed using mild and orthogonal conditions. Photo-cleavage is used for synthetic manipulation in which the compound is attached to the solid support via a photo-labile linkers. While irradiation in a standard batch photo reactor suffers from incomplete and slow cleavage, setups that rely on continuous flow and high-energy lamps are expensive, hazardous and technically challenging. One of the biggest challenges in photocleavage from solid support is that light does not efficiently penetrates to and into the porous beads. This is a major setback in the synthesis of complex molecules on solid support which requires highly efficient cleavage processes. We developed a photo-cleavage approach that uses magnetic stirring to crush the beads during or prior to irradiation. Instead of keeping the integrity of the beads, we crush them to increase the surface area exposed to irradiation. We showed that by crushing polystyrene beads equipped with photolabile linkers we expedite photo-cleavage processes. We used a simple benchtop LED lamp and quartz cuvette to achieve extremely high yield cleavage (Fig 1). Our process is straightforward and the setup is simple so that it can be done in any standard laboratory. The strategy is very valuable for cleaving complex molecules e.g. oligosaccharides from photo-labile linker on solid support.