Organotin compounds, Stille coupling

Together with reactions named after Heck and Suzuki, the Stille reac-tion belongs to a class of modern, palladium-catalyzed carbon-carbon bond forming reactions. The palladium-catalyzed reaction of an organotin compound 2 with a carbon electrophile 1 is called Stille coupling. 

The Stille reaction has developed as a popular protocol for the formation of C-C bonds due to the air- and moisture-stability as well as functional group compatibility of organotin compounds. Together with the Suzuki-Miyaura coupling it is one of the most powerful methods for the synthesis of molecules containing unsymmetrical biaryl moieties. However, despite its efficiency, this versatile reaction has slowly been displaced by other procedures that avoid the use of highly toxic organostannanes. 

In the Stille reaction, an organotin compound R1SnR3 and an organic electrophile R2X are treated with a palladium(O) or palladium(ll) catalyst, to generate the coupled product R R2 (Equation (55)).190... 

The palladium-catalyzed coupling of aiyl and vinyl halides to organotin compounds, known as Stille coupling, is one of the most important catalytic methods of carbon-carbon bond formation. The reaction is generally conducted in polar organic solvents, such as dimethylformamide, with tertiary phosphine complexes of palladium, although phosphine-free complexes or simple Pd-salts are also frequently used as catalysts [8]. 

Stille coupling was also developed in tlie early 1980s and is similar to Suzuki coupling in its sequence. It is used to couple aryl or vinyl halides or triflates with organotin compounds via oxidative addition, transmetallation, and reductive elimination. The oxidative addition reaction has tlie same requirements and preferences as discussed earlier for tlie Heck and Suzuki reactions. The reductive elimination results in formation of tlie new carbon-carbon bond. The main difference is that tlie transmetallation reaction uses an organotin compound and occurs readily without the need for an oxygen base. Aryl, alkenyl, and alkyl stannanes are readily available. Usually only one of tlie groups on tin enters into... 

As organotin compounds (organostannanes) undergo smooth Pd-catalysed transmetallation, aryl halides react with a wide variety of aryl-, alkenyl- and alkylstannanes [139]. Coupling with allylstannane is the first example [140]. The reaction is called the Migita-Kosugi-Stille or Stille coupling. Aryl, alkenyl, allyl, alkynyl and benzyl... 

In this chapter, we have already seen that C,C couplings may involve organocopper, -magnesium, -boron and -zinc compounds. But the number of suitable organometallic compounds is not exhausted. A commonly used metal for coupling purposes is tin and organotin compounds are extensively used in Stille coupling reactions. 

Dichloropyridine reacts in the dark (88% of disubstitution), whereas 2,6- and 3,5-dichloropyridines require photostimulation to afford ca. 80% yield of disubstitution products [26]. Aryltrialkylstannanes are valuable intermediates in organic synthesis, and the fact that they can be easily synthesized through the SRN1 mechanism, opens up important synthetic routes to different reaction schemes. For over a decade, the Pd(0)-catalyzed cross-coupling of organotin compounds with electrophiles, known as the Stille reaction, has been a very important tool in product design [104]. 

The Stille Reaction Coupling Reactions with Organotin Compounds ... 

Organotin compounds are used in many synthetic procedures as stoichiometric reagents (hydrostannolysis, hydrostannation, allylation, Stille coupling, Sn/Li transmetallation, transesterification, etc), and this presents the problem of removing the organotin residues from the required product. This is particularly important in the preparation of pharmaceuticals as these organotin compounds are to some degree toxic. 

The first examples of the coupling of organotin compounds were reported during the period 1976-1977, by the research groups of Eaborni and Kosugi. " The extensive synthetic and mechanistic work carried out by Stille and coworkers since 1978 soon turned this reaction into a standard methodology... 

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