When a chemical reaction is to be carried out selectively at one reactive site in a
multifunctional compound, other reactive sites must be temporarily blocked. Many
protective groups have been, and are being, developed for this purpose. A protective
group must fulfi ll a number of requirements. It must react selectively in good
yield to give a protected substrate that is stable to the projected reactions. The
protective group must be selectively removed in good yield by readily available,
preferably nontoxic reagents that do not attack the regenerated functional group.
The protective group should form a derivative (without the generation of new stereogenic
centers) that can easily be separated from side products associated with its
formation or cleavage. The protective group should have a minimum of additional
functionality to avoid further sites of reaction. All things considered, no protective
group is the best protective group. Currently, the science and art of organic synthesis,
contrary to the opinions of some, has a long way to go before we can call it a
fi nished and well-defi ned discipline, as is amply illustrated by the extensive use of
protective groups during the synthesis of multifunctional molecules. Greater control
over the chemistry used in the building of nature’s architecturally beautiful and
diverse molecular frameworks, as well as unnatural structures, is needed when one
considers the number of protection and deprotection steps often used to synthesize
a molecule.