Solid‐Phase Organic Synthesis

Solid‐phase organic synthesis (SPOS), a synthetic technique in which reaction components (eg, substrates, catalysts, and reagents) are attached to insoluble polymer supports, was introduced by Prof. Robert Bruce Merrifield in the 1960s. In the decades since its introduction, SPOS has matured into a powerful technique with applications in, for example, the synthesis of small molecules, drugs and natural products, asymmetric synthesis, and organometallic chemistry. In addition, the ease with which many SPOS reactions can be automated and run in parallel means it has a pivotal role in library synthesis for combinatorial chemistry and diversity‐oriented synthesis. This article introduces the principles of SPOS and highlights key concepts including linker units, SPOS reactions, immobilized catalysts, and solid‐supported reagents through literature examples.