Stille Cross-Coupling Reaction

In 1976, the first palladium-catalyzed cross-coupling of organotin compounds was accomplished by C. Eaborn, et al. The next year, M. Kosugi and T. Migita described the transition metal-catalyzed cross-coupling of organotin compounds with aryl halides and acid chlorides. Following this, in 1978, J.K. Stille used organotin compounds to synthesize ketones using milder reaction conditions than those used by Kosugi, but giving improved yields. In the early 1980s, Stille continued to develop and improve on his methodology, and today the palladium-catalyzed coupling reaction between an organostannane and an organic electrophile to form carbon-carbon bonds is known as the Stille cross-coupling reaction.

Despite the toxicity of the tin compounds, the Stille reaction has developed into one of the most important reactions in organic synthesis. The success of the Stille coupling derives primarily from its ability of the tin precursors to tolerate a wide variety of functional groups while also lacking sensitivity to air and moisture, unlike other reactive organometallic compounds.

The mild reaction conditions of the method are compatible with many types of functional groups, including amines, amides, esters, carboxylic acids, ketones, hydroxyl, and formyl groups, to name a few.

Among the many uses of the Stille cross-coupling reaction is the total synthesis of natural products, including the manzamine alkaloid ircinal A, and another alkaloid, quadrigemine C.