Alkyl halides Stille coupling

Collum129 reported that while the Stille coupling can proceed without using a phosphine ligand, the addition of a water-soluble ligand improved the yield of the reaction. Water-soluble aryl and vinyl halides were coupled with alkyl-, aryl-, and vinyltrichlorostannane derivatives in this way (Eq. 6.39). 

Alkynyltin compounds also take part in Stille coupling reactions with alkyl, aryl, or acyl halides or triflates (e.g., Equation (89)).251 These reactions are covered in Volume 11. 

PdCl2-, PdCl2(tppms)2- or Pd/tppds-catalysed Stille-Couplings of water soluble aryl and vinyl halides with alkyl-, aryl- or vinyltrichlorostannates (Figure 21) proceed in aqueous alkaline media to give cross-coupled products at 90-100°C with good to excellent yields.515 516... 

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... 

The reaction sequence in the vinylation of aromatic halides and vinyl halides, i.e. the Heck reaction, is oxidative addition of the alkyl halide to a zerovalent palladium complex, then insertion of an alkene and completed by /3-hydride elimination and HX elimination. Initially though, C-H activation of a C-H alkene bond had also been taken into consideration. Although the Heck reaction reduces the formation of salt by-products by half compared with cross-coupling reactions, salts are still formed in stoichiometric amounts. Further reduction of salt production by a proper choice of aryl precursors has been reported (Chapter III.2.1) [1]. In these examples aromatic carboxylic anhydrides were used instead of halides and the co-produced acid can be recycled and one molecule of carbon monoxide is sacrificed. Catalytic activation of aromatic C-H bonds and subsequent insertion of alkenes leads to new C-C bond formation without production of halide salt byproducts, as shown in Scheme 1. When the hydroarylation reaction is performed with alkynes one obtains arylalkenes, the products of the Heck reaction, which now are synthesized without the co-production of salts. No reoxidation of the metal is required, because palladium(II) is regenerated. 

Metallated 1-ethoxy-1,3-dienes 697 and 712, obtained from the corresponding acetals by means of the LICKOR base, have been treated with alkyl halides, epoxides, carbonyl compounds, carbon dioxide and carboxylic esters affording ( )-l-substituted 1-ethoxy-1,3-dienes and, after hydrolysis, a,P-unsaturated carbonyl compounds1007-1010 (Scheme 186). Intermediates 697 and 712 have been transformed into the corresponding vinyl stan-nanes, which were submitted to Stille couplings with iodobenzene and benzoyl chloride823. 

It should be stressed that growing species with diffused charge distributed along —N—C—0— group are relatively weak electrophiles. Thus, as discussed in Section II.B.6.C, ionic active species may exist when coupled with relatively nucleophilic counterions such as Br or I". The collapse of ion pairs into covalent alkyl halide end groups does proceed in the system, but these covalent species still react (although slower than... 

The coupling of alkyl halides by treatment with sodium to give a symmetrical product is called the Wurtz reaction. Side reactions (elimination and rearrangement) are so common that the reaction is seldom used. Mixed Wurtz reactions of two alkyl halides are even less feasible because of the number of products obtained. A somewhat more useful reaction (though still not very good) takes place when a mixture of an alkyl and an aryl halide is treated with sodium to give an alkylated aromatic compound (the Wurtz-Fittig reaction)... 

The reactions have a very wide scope. Acyl halides serve as substrates for Stille couplings in addition to the usual aryl and alkenyl halides however, most alkyl halides cannot be used as substrates. Like Pd-catalyzed carbonylations, reactions proceed most quickly when X = I and rather slowly when X = Cl, although especially bulky phosphine ligands such as /-Bu3P allow even aryl chlorides to undergo coupling at room temperature. Again, triflates are also widely... 

The stannylene Sn[N(TMS)2]2 undergoes oxidative addition with halides RX, where R = alkyl, allyl, allenyl, hexynyl, phenyl, or styryl, to give the Sn(IV) compounds, RSnX[N(TMS)2]2, then these can be used in Stille coupling reactions where the organo-tin(IV) compound is activated by fluoride ion 49-51... 

Recently it was shown that intramolecular coordination at tin in tetraorganotin compounds promotes the transfer of an organic group from tin to an organic halide in the Stille coupling reaction. In the presence of a Pd catalyst, the exocyclic alkyl group of l-aza-5-alkyl-5-stannabicyclo [3.3.3]undecane selectively couples with aryl or alkenyl halides (111) ... 

A simple way to avoid toxic and intractable triorganotin waste is to use monoorganotin reagents that are much less toxic and less lipophilic. Unactivated secondary alkyl halides can be coupled with aryl-trichlorotin in a nickel-catalyzed Stille cross-coupling reaction" (e.g. Scheme 5.8.15). 

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