Solubilising groups: a conceptual equivalent of protecting groups in organic synthesis

In this brief essay, one of the most common and least appreciated challenge in the field is addressed. Few chemists, particularly supramolecular chemists, exist who are not all too familiar with solubility problems during the synthesis of new molecules. Solubility problems are inherent to the synthesis of molecules that are made to build supramolecular architectures because the same intermolecular interactions that cause the problem are later on essential for the final self-assembly of the system of interest. Naturally, many solutions exist for a problem that occurs so frequently. They are used as daily routine in many laboratories, the temporary attachment of hydrophobic bulk of various size and nature being the most common. However, contrary to the comparable situation with protecting groups, these solubilising groups are generally underappreciated, often communicated orally as one of those precious 'lab secrets' that nobody really takes serious but everybody really needs to get things running and reach the relevant part of the research project. Here, we briefly try to summarise latent concepts concerning solubilising groups, focusing particularly on questions concerning quantitative aspects and the removal of solubilising groups for self-assembly with pre-, post- or in situ desolubilisation, and provide a simple practical example with tert-butyldiphenylsilyl as an illustrative solubilising group.