The interplay of invention, discovery, development, and application in organic synthetic methodology: a case study.

This Perspective chronicles the conceptual development, proof of principle, exploration of scope, mechanistic investigations, and applications in natural product total synthesis of palladium-catalyzed cross-coupling reactions of silicon derivatives. The explication of how this new class of cross-coupling reactions evolved from problem formulation to use in complex molecule synthesis serves as one goal of the essay. The other goal is the presentation of the various stages of this methodological enterprise such that the reader gleans a first hand look at one approach to the creation of new synthetic reactions. These two goals are woven together such that the underlying thought processes that guide a program of reaction development emerge in clear view and imbue the chemical tapestry with a cohesive logic.