Stannanes Stille coupling reaction

The Stille reaction of 2-chloro-3,6-diisopropylpyrazine (7) and 2-chloro-3,6-diisopropylpyrazine 4-oxide (9) with tetra(p-methoxyphenyl)stannane (readily prepared in situ from the corresponding Grignard reagent and SnCU) led to the corresponding arylation products 8 and 10, respectively [9]. Additional Stille coupling reactions of chloropyrazines and their N-oxides have been carried out with tetraphenyltin [10] and aryl-, heteroaryl-, allyl- and alkylstannanes [11]. 

A number of Stille coupling reactions have been reported by Handy et al. [95], With PdCl2(PhCN)2/Ph3As/CuI in [BMIM][BF4], good yields and good catalyst recyclability (up to five times) were reported for the reachon between a-iodenones and vinyl and aryl stannanes (Scheme 5.2-19). However, the reported reaction rates were significantly lower than those obtained in NMP. 

If 2,3-dibromo propene is used as an allylic substrate the substitution product 71 can be either isolated or, after addition of additives and adjustment of the reaction conditions, 71 can readily react in cross-coupling reactions with alkynes (Sonogashira coupling), stannanes (Stille coupling), or boronic acids and boronates (Suzuki coupling) to provide the sequential allylic substitution-cross-coupling products 72-78 in moderate to good yields (Scheme 23). 

The palladium-catalyzed cross-coupling reactions of boronates as well as boranes (Suzuki coupling) and stannanes (Stille coupling), which are mechanistically related to the Heck reaction, are discussed in Chapters 2 and 4. 

On the other hand, structurally similar compounds 83 were potent vascular endothelial growth factor (VEGF) receptor inhibitors with antitumor activities. The key intermediate 82 was prepared using a Stille coupling reaction of stannane 81 and 2,6-dichloropyrazine. ... 

Vinylation can also be done by Pd-catalysed cross-coupling in which one component is used as a halide or triflate and the other as a stannane (Stille reaction) or boronic acid (Suzuki reaction). Entry 9, Table 11.3, is an example of the use of a vinylstannane with a haloindole. lndole-3-boronic acids, which can be prepared by mcrcuration/boration, undergo coupling with vinyl triflates (Entry 10). 

These workers also synthesized tryptamine stannane 161 and effected Stille couplings with this compound, including the intramolecular reaction 162 to 163 [171]. Eight- and 9-membered rings could also be fashioned in this manner. Other Pd catalysts were much less successful. The N-tosyl derivative of 162 was similarly prepared and used in Stille chemistry. 

Numerous stannanes have been coupled with halopyridines as electrophiles in the Stille coupling. One of the simplest of these is vinylstannane [82-84]. The Stille reaction of bromopyridine 95 with tributylvinyltin gave angustine (96) [84], an indolopyridine alkaloid. Bromopyridine 95 also took part in a three-component carbonylative-Stille coupling sequence to provide an entry to another indolopyridine alkaloid, naucletine (97) [84]. 

Recently, Li successfully conducted the Suzuki and Stille reactions on the pyrazine ring of 3-bromoquinoxalin-2-ylamines [51]. Indolylquinoxaline 92 was obtained from the union of 3-bromoquinoxalin-2-ylamine 90 and l-phenylsulfonyl-2-tri-n-butylstannyl-l//-indole (91). A wide variety of heterocyclic stannanes bearing various functional groups underwent Stille coupling with 90 under the same conditions to give the corresponding adducts in 72-98% yields. 

In the more prolific aspect of the Stille couplings involving a pyrimidine fragment, pyrimidinyl halides or triflates have been coupled with a variety of stannanes. When there is only one reactive halide on the pyrimidine ring, the reaction outcome is straightforward with no regiochemical concern. The simpler stannanes are vinyl stannanes [35-37]. More complicated variants include stannylquinones [38] and l-(trialkylsilyloxy)vinyltin [39] as illustrated by the synthesis of 66. 

The heteroaromatic stannanes undergo the normal electrophilic substitution reactions of their protic precursors, and often to an enhanced degree. They are often prepared with the aim of a subsequent Stille cross-coupling reaction, and oligothiophenes with potentially useful optical and electron properties have been prepared by coupling between stannyl- and bromo-thiophenes, for example, Equation (63).204... 

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