What is a Stille coupling reaction and how does it work?
A Stille coupling reaction is a chemical reaction catalyzed by palladium that is used
frequently in organic synthesis and C—C bond formation. It involves the coupling of an
organotin compound (chemical compound comprised of tin and hydrocarbon substituents,
also known as stannanes) with an sp2-hybridized organic halide or pseudohalide. A general
reaction formula for a Stille coupling is
X is usually a halide (Cl, Br, I), but it can also be a pseudohalide (i.e., CF3SO3-). This reaction
is generally done using degassed solvents to avoid the oxidation of the palladium catalyst,
which would produce a decreased yield of the intended cross-coupling reaction by
promoting homo-coupling of the stannyl compounds.
To catalyze this reaction, palladium catalysts are used. If the Pd source itself does not
contain strong enough ligands, phosphine ligands such as tri-2-furylphospine and
triphenylarsine are added.
Reaction Mechanism
The first step of the Stille coupling reaction is the reduction of the Pd catalyst from Pd(II)
to an active Pd(0) species. The organohalide is then added through oxidative addition
and a cis intermediate is formed. However, this intermediate is quickly isomerized to a
trans intermediate. The organotin compound is then added and forms an intermediate
through transmetalation (ligands are switched between two metal centers). After reductive
elimination, the product of the coupling reaction and the active Pd(0) species is yielded.
(Stereochemistry is retained in both oxidative addition and reductive elimination.)
To see how a Stille coupling reaction synthesizes molecule 76 from molecule 75, click here.
