Palladium in Heterocyclic Chemistry 25Stannane couplings (Stille reaction)
Couplings with HetSnR 3 are particularly useful in cases where the corresponding boronic acid would be unstable, for
example some azole boronic acids. However, all of the variations equivalent to the boronic acid couplings can be used.
Stannane couplings suffer from the disadvantage that organotin compounds tend to be toxic and environmentally
hazardous. In particular, trimethyltin compounds are very toxic to humans and organotin compounds generally are
highly toxic to many aquatic organisms and are therefore subject to stringent regulatory control concerning aqueous
effl uents. Organotin compounds are lipophilic and are therefore readily absorbed through the skin.
Cross-couplings using other organometallic reagents
Grignard reagents are useful partners (Kumada–Corriu reaction) when functional groups are absent but the correspond-
ing zinc reagents (Negishi reaction) are more tolerant of functional groups and can often give better yields. Nickel is a
good replacement for palladium in some reactions. Silanes can also be useful partners (Hiyama–Denmark reaction).