The reaction is now widespread in synthetic organic chemistry.
The Stille coupling was discovered in 1977 by John Kenneth Stille and David Milstein . In 1992, Stille couplings had been used in 50% of all published syntheses containing cross-coupling reactions . The reaction is currently being further developed, especially with a view to its application in the industrial synthesis of pharmaceuticals. The high tolerance of functional groups in particular makes the Stille coupling attractive for the synthesis of complex structures.
Since oxygen both causes the oxidation of the palladium catalyst and promotes homocoupling of the organotin compounds, the reaction must be carried out under an inert gas atmosphere and in an absolute solvent.
A trimethylstannyl or tributylstannyl compound is usually used as the organotin compound. Although the trimethylstannyl compound shows higher reactivity as compared with the tributyl compound, the former is reluctant to use because it shows 1,000 times more toxicity. Therefore, trimethylstannyl compounds are only used if absolutely necessary. The tendency of the organic residues to transfer decreases with decreasing s character; sp³-hybridized residues are often referred to as "dummy residues" because they are not transferred in the presence of residues with a higher s character.
The ligands bound to the palladium also have an influence on the reaction. The weaker a ligand coordinates to the palladium, the faster the reaction proceeds.
The reaction mechanism of the Stille coupling has been largely clarified. In a first step, the palladium catalyst ( 1 ) is reduced to the active Pd (0) species ( 2 ). The oxidative addition of the organohalide ( 3 ) gives the cis intermediate which isomerizes rapidly to the trans intermediate 4 . Transmetalation with the organostannane ( 5 ) forms the intermediate 7 , which after reductive elimination gives the product ( 8 ) and regenerates the active Pd (0) species ( 2 ). Oxidative addition and reductive elimination preserve the stereochemical configuration of the reactants.
To increase the yield of the reaction, lithium chloride is often added to the reaction mixture . This stabilizes the intermediate formed in the oxidative addition and thus accelerates the reaction.
The reactivity and specificity of the Stille coupling can be increased by adding stoichiometric amounts of copper (I) or Mn (III) salts.
In the presence of the Cu (I) salts, palladium on carbon (Pd / C) shows a high catalytic activity.
A new study shows a palladium-free reaction mechanism of the Stille coupling. The coupling takes place radically, using an organic photocatalyst.
The atomic economy of the Stille coupling is low, which makes its possible technical use - with a few exceptions - unattractive.
- AF Renaldo, JW Labadie, JK Stille: Palladium-Catalyzed Coupling of Acid Chlorides with Organotin Reagents: Ethyl (E) -4- (4-Nitrophenyl) -4-Oxo-2-Butenoate In: Organic Syntheses . 67, 1989, p. 86, doi : 10.15227 / orgsyn.067.0086 ; Coll. Vol. 8, 1993, p. 268 ( PDF ).
- JK Stille: Angew. Chem. Int. Ed. Engl. 25, 1986, pp. 508-524, doi: 10.1002 / anie.198605081 .
- V. Farina, V. Krishnamurthy, WJ Scott: The Silent Reaction. In: Org. React. 50, 1998, pp. 1-652.
- TN Mitchell: Synthesis. 1992, pp. 803-815, doi: 10.1055 / s-1992-26230 .
- Silent reaction handout ( Memento from June 22, 2006 in the Internet Archive ) of the Myers group. (PDF file; 397 kB)
- Silent reaction on organic-chemistry.org
- M. Kosugi, K. Sasazawa, Y. Shimizu, T. Migita: REACTIONS OF ALLYLTIN COMPOUNDS III. ALLYLATION OF AROMATIC HALIDES WITH ALLYLTRIBUTYLTIN IN THE PRESENCE OF TETRAKIS (TRIPHENYLPHOSPHINE) PALLADIUM (O), Chem. Letters. 1977, p. 301, doi: 10.1246 / cl.1977.301 .
- D. Milstein, JK Stille: J. Am. Chem. Soc. 100, 1978, p. 3636, doi: 10.1021 / ja00479a077 .
- WJ Scott, GT Crisp, JK Stille: Palladium-Catalyzed Coupling of Vinyl Triflates with Organostannanes: 4-tert-Butyl-1-Vinylcyclohexene AND 1- (4-tert-Butylcyclohexen-1-yl) -2-propen-1- one In: Organic Syntheses . 68, 1990, p. 116, doi : 10.15227 / orgsyn.068.0116 ; Coll. Vol. 8, 1993, p. 97 ( PDF ).
- JK Stille, AM Echavarren, RM Williams, JA Hendrix: 4-methoxy-4'-nitrobiphenyl In: Organic Syntheses . 71, 1993, p. 97, doi : 10.15227 / orgsyn.071.0097 ; Coll. Vol. 9, 1998, p. 553 ( PDF ).
- AL Casado, P. Espinet: J. Am. Chem. Soc. 120, 1998, pp. 8978-8985, doi: 10.1021 / ja9742388 .
- AL Casado, P. Espinet: Organometallics. 17, 1998, pp. 954-959.
- LS Liebeskind, RW Fengl: J. Org. Chem. 55, 1990, p. 5359.
- V. Farina, S. Kapadia, B. Krishnan, C. Wang, LS Liebeskind: J. Org. Chem. 59, 1994, p. 5905.
- LS Liebeskind, E. Peña-Cabrera: Stille Couplings Catalyzed by Palladium-on-Carbon with CuI as a Cocatalyst: Synthesis of 2- (4'-Acetylphenyl) Thiophenes In: Organic Syntheses . 77, 2000, p. 135, doi : 10.15227 / orgsyn.077.0135 ; Coll. Vol. 10, 2004, p. 9 ( PDF ).
- GP Roth, V. Farina, LS Liebeskind, E. Peña-Cabrera: Tetrahedron Letters . 36, 1995, p. 2191.
- Saman Ghasimi, Simon A. Bretschneider, Wei Huang, Katharina Landfester, Kai AI Zhang: A Conjugated Microporous Polymer for Palladium-Free, Visible Light-Promoted Photocatalytic Stille-Type Coupling Reactions . In: Advanced Science . S. n / a – n / a , doi : 10.1002 / advs.201700101 .