Stille reaction transmetallation

The general catalytic cycle of the Stille reaction involves oxidative addition, transmetallation, and reductive elimination. 

The basic mechanism of the Stille reaction involves transmetallation, either directly or via an organocopper intermediate, with a Pd(H) intermediate generated by oxidative addition from the aryl halide or triflate. 

Pyridylstannanes are accessed by transmetallation of pyridyllithium reagents with trialkyltin halides such as tributyltin chloride <20000L3373, 1998JA2805> and typically utilized as coupling partners in Stille reactions with... 

Fig. 8. ESI(+)-MS of the Stille reaction of 3,4-dichloroiodobenzene and vinyl-tributyltin in acetonitrile mediated by Pd(PPh3)4. A radical cation intermediate undergoing transmetallation is observed at m/z 958.

A second important palladium-catalyzed process is cross coupling of an aryl or alkenyl tiaUcyltin reagent with an aUcyl or aryl halide. In this reaction, one carbon-palladimn bond is generated by transmetalation of Pd -X with BU3 Sn-R, while the other carbon-palladium bond is formed by oxidative addition of an organic halide with a Pd°L species. This reaction, which is tolerant of many organic functional groups, is normally known as the Stille Reaction (Scheme 4). ... 

The palladium-catalyzed cross-coupling reaction of a vinyl or aryl stannane with an arylhalogenide or -triflate is known as a Stille reaction. The mechanism of this Stille reaction is outlined below The palladium precatalyst loses two ligands and forms the catalytic species 36. The catalytic cycle starts with the oxidative addition of the catalytic species 36 into the carbon-triflate bond of 23 forming complex 41, which, however, does not undergo the required transmetallation step with stannane 22. Therefore, the triflate ion is... 

When the Stille reaction is carried out under a CO atmosphere, the carbonylative coupling proceeds in a manner similar to that described for the Suzuki reaction namely, carbonyl insertion into the Pd-C bond of the oxidative addition complex. Transmetalation, followed by ds-trans-isomerization and reductive elimination, generates the ketone product. " ... 

The detailed discussion of transmetallation reactions with organolithium compounds (1, XM = RLi), and coupling reactions (5) in the presence of transition metal catalysts (particularly the Stille reactions) is deferred until Sections 22.1 and 22.2. 

Stille reactions of FcSn0i and FcSnn with heterocyclic halides RX give the substituted ferrocenes (RCsH Fe sHs) and (RCsH Fe.129-131 Butyllithium reacts with FcSnn by mono- and di-transmetallation, but BC13 surprisingly gives a rearranged product.132... 

Organic Synthesis Tin/lithium Transmetallation, the Stille Reaction... 

The other step with stereochemical consequences is the transmetalation step. The enantioselective synthesis of tin derivatives with chiral carbons attached at tin is not easy, and the transfer of alkyl groups is more difficult than that of aryl or sp there are only three reports in the literature where groups with a stereogenic sp carbon attached to tin have been successfully transferred in a Stille reaction. 

The first two and last two steps for the catalytic cycle of Suzuki cross-coupling are much the same as those for the Stille reaction (Scheme 12.18) the transmeta-lation step, however, is unique. Transmetalation involves transfer of R to Pd from a borane, borate ester, or boronic acid. Both recent experimental investigations and analysis using DFT calculations indicate that transmetalation is not simply a concerted process as suggested by transition state structure 38. 

A tributylstannyl group can also be introduced via transmetalation. Collins trans-metalated the trimethylsilyl group of the l,2,4-triazolo[4,3-/>]pyridazine 162 to the corresponding tributylstannane 163 using (Ihi Snj O [35]. Subsequent Stille reaction of 163 with iodobenzene in the presence of Pd(PPh3)4 in DMF at 100°C resulted in the formation of 164, albeit in a low overall yield. In the same paper, a reverse approach was presented in which a brominated triazolopyridazine 165 reacted with 2-tributylstannyl-1,3-oxazole to yield 6-[(l-methyl-l//-l,2,4-triazol-5-yl)methoxy]-7-(l,3-oxazol-2-yl)-3-phenyl[l,2,4]triazolo[4,3-Z ]pyridazine 166 in 37% yield (23% of starting compound was also recovered). 

The generally accepted catalytic cycle for the Buchwald-Hartwig amination mirrors that of other palladium catalyzed cross-coupling reactions.10 11 irThere is an oxidative addition (A to B), followed by an exchange on palladium (B to C), and finally a reductive elimination (C to D and A). The main difference involves the exchange step. In a Suzuki, or Stille, reaction this step proceeds through a discrete transmetallation event, whereas... 

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