Vinylstannanes, Stille coupling

The palladium-catalyzed coupling of aryl iodides with vinylstannanes (Stille coupling) leads to the formation of styrenes. With resin-bound vinylstannanes, this reaction can be conducted in such a way that simultaneous detachment from the support of the newly formed styrenes occurs. This has been realized intramolecularly in the preparation of macrocyclic lactones (Entry 4, Table 3.43). The required resin-bound vinylstannanes were prepared either by hydrostannylation of alkynes with a resin-... 

Scheme 32. Stille couplings of regioselectively generated enol triflates with a vinylstannane.

The synthesis of the key intermediate aldehyde 68 is outlined in Schemes 19-21. The two hydroxyls of butyne-l,4-diol (74, Scheme 19), a cheap intermediate in the industrial synthesis of THF, can be protected as 4-methoxybenzyl (PMB) ethers in 94% yield. The triple bond is then m-hydrostannylated with tri-n-butyl-tin hydride and a catalytic amount of Pd(PPh3)2Cl238 to give the vinylstannane 76 in 98 % yield. Note that the stereospecific nature of the m-hydrostannylation absolutely guarantees the correct relative stereochemistry of C-3 and C-4 in the natural product. The other partner for the Stille coupling, vinyl iodide 78, is prepared by... 

Martin prepared 5-trimethylstannylindole and effected coupling with bromobenzene to give 5-phenylindole [125], In a search for new cAMP phosphodiesterase inhibitors, Pearce prepared the furylindole 190 from 5-bromoindole and 5-ferr-butoxy-2-trimethylstannylfuran [196a], Benhida and co-workers explored Stille couplings of 6-bromo- and 6-iodoindole, and methyl 6-iodoindol-2-ylacetate with a variety of heteroarylstannanes and vinylstannanes [196b]. 

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]. 

Stille couplings also have been exploited in the synthesis of the aromatic macrocyclic core of diazonamide A (2) [5, 20]. Pattenden s group utilized the Pd-catalyzed coupling between the 3-stannyl substituted indole 23 and the 3-bromooxazole 24 to provide a particularly expeditious route to the ring system 25 [20]. In addition, Harran s group secured the connection between bromooxazole 12 and vinylstannane 26 also using a Stille coupling [5]. 

The Stille reaction was also effective in the coupling of two sensitive substrates. The functionalised dihydropyrrole and vinylstannane shown in 6.29. were reacted under very mild conditions to give, after an acidic workup, the 2-acylpyrrole derivative.39 The palladium catalyst contained the less strongly coordinating triphenylarsine ligand instead of triphenylphosphine, a trick commonly used to increase the efficiency of the Stille coupling. 

The intermolecular Heck reactions of oxazoles and thiazoles with olefins are not too common. They are rarely high yielding since in several cases they are biased by dehalogenation. Due to this reason the olefination of these systems is usually achieved through Stille coupling with vinylstannanes. 

Similarly, vinylstannanes can also yield products of cine-substitution (Scheme 8.17), specially if tin and an electron-withdrawing or aryl group are bound to the same carbon atom [40, 137-141]. It has been suggested that formation of these products proceeds via intermediate formation of a palladium carbene complex [138, 140] or via reversible /3-hydride elimination [141], and can be avoided by addition of Cu(I) salts [142], which increase the rate of Stille coupling, or by protecting vinylic C-H groups by transient silylation [143]. 

The total synthesis of Galubulimima alkaloid 4,4a-didehydrohimandravine, using an intramolecular Diels-Alder reaction and a Stille coupling as the key steps, was accomplished in the laboratory of M.S. Sherburn. The required vinylstannane intermediate for the Stille coupling was prepared via the one-pot Corey-Fuchs reaction, followed by radical hydrostannylation. 

The first enantioselective total synhesis of (-)-strychnine was achieved by L.E. Overman and co-workers. The carbon skeleton of the main precursor for the key aza-Cope rearrangementMannich cyclization was assembled by applying a Pd ° -catalyzed carbonylative Stille coupling reaction. Thus, the cyclic vinylstannane was coupled with the triazinone-protected ortho-iodoaniline to afford 80% yield of the aromatic enone using Pd2(dba)3 as the catalyst in the presence of carbon monoxide. 

Stille coupling. Vinyl-vinyl coupling and S 2 displacement of allylic carbonates with vinylstannanes, the latter in an aqueous medium, give rise to 1,3- and 1,4-dienes, respectively. 

In organic synthesis, the preparation of most vinylstannanes is aimed at tin/lithium transmetallation (equation 8-33), or at Stille coupling reactions (equation 8-34). These reactions are discussed in Sections 22.1 and 22.2, respectively, and the remaining reactions are covered in this section. 

A number of (Z)-9-(heteroarylmethylene)-7-azatricyclo[4.3.1.0 A]decanes were synthesized to evaluate their activities at dopamine, serotonin, and norepinephrine receptors. The Stille coupling of vinylstannane 38 with 2-pyrazinyl bromide in the presence of Pd2(dba)3 and AsPh3 gave the pyrazine derivative 39 in moderate yield [27]. The yields were significantly improved with AsPh3 ligand. 

Acid hahdes can also be used in Migita-Kosugi-Stille coupling in this C-C bond formation fhe corresponding ketone is produced. Subjection of a benzoyl chloride derivative prepared in situ to cross-couphng with a vinylstannane provided the desired vinyl ketone which was successfully transformed to a potent COX-2 inhibitor (Scheme 12.99) [201],... 

Intramolecular coupling of 120 having an aryl iodide group and a vinylstannane group accomplished the total synthesis of (-)-zealarenone (99) (Scheme 19) [77]. The first total synthesis of macrolactin A (124) was efficiently accomplished based on the Stille reaction of 122 for both stereospecific construction of the diene moieties and closure of the 24-membered macrocyclic ring [78]. The key precursor 122 was synthesized via two Stille couplings and Mitsunobu esterification. An alternative route to the dimethyl ether 125 was reported by cyclization of 123, which was prepared by the Stille and Suzuki couplings followed by DCC-DMAP esterification... 

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