Stille-Kelly coupling

Intramolecular coupling of aryl halides and vinyl triflates  

R R = alkyl, aryl, electron-withdrawing or electron-donating R = Me, n-Bu X = Br, I, OTf 

The Stille-Kelly coupling consists of two connected catalytic cycles and the following steps 1) the oxidative addition of the Pd ° complex into one of the C-X bond of the aryl halide 2) transmetallatlon with the distannane followed by reductive elimination to afford the organostannane 3) oxidative addition of the Pd ° complex into the C-X bond of the organostannane 4) intramolecular transmetallatlon, and 5) reductive elimination to give the coupled product. 

Li and co-workers synthesized all four possible benzo[4,5]furopyridines via two different Pd-catalyzed approaches. In one of the routes the precursor biaryl compound was prepared by the SwAr reaction of 3-iodo-4-chloropyridine with ort/io-iodophenoxide. The resulting diiodo heterobiaryl ether was cyclized under Stille-Kelly coupling conditions in refluxing xylene. 

The total synthesis of the pyrrolophenanthridine alkaloid, hippadine, was accomplished in the laboratory of T. Sakamoto. The last and key step of the synthetic sequence was the Stille-Kelly coupling of the A/-benzoylated indole precursor in 68% yield. 

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Pd-catalyzed Stille-Kelly coupling Pd-catalyzed intramolecular biaryl coupling of aryl halides or aryl triflates in the presence of distannanes. 440... 

Related reactions Kumada cross-coupling, Negishi cross-coupling, Stille coupling, Stille-Kelly coupling, Suzuki cross-coupling ... 

In Grigg s approach to hippadine (37), he established the connection between the two phenyl rings via the Stille-Kelly reaction [45]. When diiodide 35 was submitted to the Pd(0)/ditin catalyst system, the intramolecular cyclization was realized to establish the C—C bond in lactam 36. Oxidation of the indoline moiety in 36 using 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) then delivered hippadine (37). Analogously, the intramolecular Stille coupling of dibromide 38 led directly to hippadine (37) [46]. 

Novel phenanthro[9,1 ()-r/ isoxazoles 37 have been prepared by intramolecular Stille-Kelly stannylation/coupling of o,o -diiodo-4,5-diarylisoxazoles and by PIFA-mediated non-phenolic oxidative coupling of the corresponding non-halogenated substrates <02T3021>. 

The Stille-Kelly reaction is a variant of the Stille coupling where an organodihalide undergoes an intramolecular reaction in the presence of hexamethylditin and a palladium catalyst. 

Aryl-aryl cyclizations were used for the preparation of polyaromatic compounds, cryptands and heterocydes. A particularly interesting version is the Still-Kelly cyclization that was used for the synthesis of phenanthro [9,10-d]pyrazoles involving the intermolecular formation of the aromatic stannane followed by an intramolecular coupling with the aryl halide moiety [128]. Benzo [4,5]furopyri-dines [129] and dibenz [c,a]azepines [130] were prepared by related intramolecular coupling of diodides in the presence of hexamethylditin. 

In the model studies toward the total synthesis of dimethyl sulfomycinamate, Kelly et al. successfully carried out the Stille couplings of oxazolyl triflate 18 with an array of organostannanes [19, 20]. Thus, 2-aryl-4-oxalone 17 was transformed into the corresponding triflate 18, which was then coupled with 2-trimethylstannylpyridine under the agency of Pd(Ph3P)4 and LiCl to provide adduct 19. The couplings of triflate 18 with phenyl-, vinyl- and phenylethynyl trimethyltin all proceeded in excellent yields. Unfortunately, application to the more delicate system in the natural product failed and the oxazole moiety was installed from acyclic precursors. 

Scheme 34. Stille coupling of (hetero)aryl halides with (hetero)aryltin reagents Kelly s molecular brake (68, [22]) and nicotelline (69, [124a]) a) Pd(PPh3)4,b) xylene, A...

To functionalize the C5 position, Williams and Fu developed a 2-phenylsulfonyl substituted oxazole. The C5 position of this oxazole can be cleanly deprotonated with LDA and trapped with either NIS or NBS to form the 5-iodo- or 5-bromo-2-phenylsulfonyloxazole in good yield. The same report details that the 2-phenylsulfonyl group can subsequently be displaced with alkyl, alkenyl, or aryl lithium reagents to form 2,5-disubstituted oxazoles efficiently. A triflate at the C5 position can be prepared from the corresponding oxazolone however, the oxazolone decomposes at room temperature, and Kelly reported that attempted Stille coupling with C5 triflates failed due to decomposition of the triflate. ... 

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