Stille Coupling

Stille Coupling; discovered by John Stille, allows for the stereospecific coupling of an organostannans with aryl and vinyl halides or triflates even with the presence of other functional groups such as carboxylic acids, amides, esters, nitro groups, ethers, amines, hydroxyl groups, ketones, and aldehydes. For Stille coupling to occur, a suitable palladium catalyst, organostannane (a compound with a C-Sn bond), and an organic electrophile reacts to form a C-C s bond. The general scheme of Stille coupling is shown below:     

The coupling partners (R and R’) can be aryl or vinyl groups, and X can be a halogen (Cl, Br, or I) or a triflate (OTf). Under those conditions the s bond formed would be between two sp2 – hybridized centers as in the following reactions. Sp3 and sp2 hybridized centers can be formed using Stille coupling through the use of an allylic or benzylic stannane,

Stile coupling has excellent functional group tolerance, and is resistant to strong oxidants. It uses air and moisture stable organostannates in the reaction. 

Suitable palladium catalyst

Transitions metals including xyx are commonly reacted with molecules or ions to function as catalysts. Particularly, palladium (Pd) catalysts have been known to react with ligands to give transition metal complexes. It is also known that valence shell of transition metal elements can accommodate 18 electrons (valence shell is made up of one s orbital, three p orbitals, and five d orbitals). Therefore, a coordinately saturated transition metal contains 18 electrons. Palladium has 10 valence electrons when the oxidation state is 0, and so if it were coordinated with four ligands, it would have a total of 18 electrons. That is each of the ligands provides two valence electrons and palladium provides 10 valence electrons such as Pd(PPh₃)₄. Conversely a palladium atom with fewer than 18 electrons is said to be coordinatively unsaturated, thus more reactive.

Mechanism for Stille coupling: oxidative addition, transmetallation, and reductive elimination.

1. Oxidative Addition: Appropriate halide/triflate (R’X) reacts with active palladium complex to yield a complex in which both R’ and X are bounded directly to palladium.

2. Transmetallation: The R group from the organostanne and the electrophile(X) of the palladium complex are swapped. “Transmetallation” refers to the R group from one metal (Sn) being transferred to another metal (Pd). It is known as the rate-determining step of the overall coupling reaction and is based on the identity of the R group as followed:

vinyl > aryl > allyl ~ benzyl > > > > alkyl

The much slower rate of migration of aslkyl groups on the organostannanes compared to the vinyl, aryl, allyl, or benzyl allows for selective migration of the R group during the transmetallation step.

3. Reductive Elimination: Oxidation state of the palladium is reduced, regenerating the active Pd(0) catalyst, PdL2 when R and R’ are released from the palladium complex.  A new s bond between the coupling partner is formed.

Catalytic Cycle: