Stille reaction

The Stille coupling is a palladium -catalyzed chemical coupling an organotin compound ( organostannanes ) with an sp2 -hybridized organic halide.

Implementation

The reaction is now widely used in synthetic organic chemistry.

X is typically a halide such as chlorine, bromine, iodine or a pseudohalide such as triflate, CF3SO3 -.

The Stille coupling was discovered in 1977 by John Kenneth Stille and David Milstein. Stille couplings were in 1992 50% of all published syntheses that contained cross - coupling reactions have been used. The reaction is currently being developed, especially in regard to the application in the industrial synthesis of pharmaceuticals. Especially the high tolerance of functional groups makes the Stille coupling attractive for the synthesis of complex structures.

Since both the oxygen oxidation of the palladium catalyst caused as also promotes homo coupling of the organotin compounds, the reaction under an inert gas atmosphere and in solvent of absolute must be performed.

As organotin compound is used as a rule a trimethylstannyl or Tributylstannylverbindung. Although the comparison with the Trimethylstannylverbindung Tributylverbindung shows a higher reactivity, is used former reluctant because it is a 1000 times more toxic. Therefore, we only used Trimethylstannylverbindungen when it is absolutely necessary. The transfer tendency of the organic radicals decreases with decreasing s character; sp ³ -hybridized residues are often referred to as "dummy residues " because they are not transferred in the presence of residues with higher s- character.

The bound on the palladium ligands also influence the reaction. A ligand coordinated to the weaker the palladium, the faster the reaction.

Reaction mechanism

The reaction mechanism of the Stille coupling is largely aufgeklärt.In a first step, the reduction of the palladium catalyst (1) to the active Pd ( 0) species (2). The Oxidative Addition of organohalide (3 ) gives the cis- intermediate, which rapidly isomerizes to the trans - intermediate 4. Transmetalation with organostannane (5) forms the intermediate 7, which after reductive elimination, the product ( 8) and results in the active Pd (0 ) species, (2) regenerates. The oxidative addition and reductive elimination to preserve the stereochemical configuration of the reactants.

Rate of ligand transfer ( transmetallation ) of tin: alkynyl > alkenyl > aryl > allyl benzyl = > α - alkoxyalkyl > alkyl

Variations

To increase the yield of the reaction, to the reaction mixture often is lithium chloride. This stabilizes the intermediate formed in the oxidative addition, thus accelerating the reaction.

Reactivity and specificity of the Stille coupling, by the addition of stoichiometric amounts of copper (I) - can be increased, or Mn (III ) salts.

In the presence of Cu (I ) salts of palladium is on charcoal ( Pd / C ) has a high catalytic activity.

Criticism

The atom economy of the Stille coupling is small, the possible technical use - of exceptions - unattractive.