4 - Combinatorial solid-phase synthesis

Abstract

In solid-phase synthesis, a large excess of reagents may be employed to drive reactions to completion and the excess of reagents may be removed by filtration, thus eliminating the tedious workup often associated with organic synthesis in solution. Since general and high-yielding reactions can be performed on solid support, solid-phase synthesis is particularly well suited to library generation involving multistep transformations. This chapter provides literature procedures and references for condensations, and describes carbon-carbon bond formation, Mitsunobu and substitution reactions, and oxidations and reductions on solid support. Examples of specific reactions on solid support ranging from amide bond formation to the palladium-catalyzed amination of support-bound aryl halides are provided. The solid-phase synthesis of heterocyclic compounds is also explained.