Stille couplings/reactions

Schollkopf, U. Ludwig, G. Ostermann, M. Patsch, Tetrahedron Lett. 1969, 3415-3418. 

Coupling reaction of organotin compounds with carbon electrophiles 

Together with reactions named after Heck and Suzuki, the Stille reac-tion belongs to a class of modern, palladium-catalyzed carbon-carbon bond forming reactions. The palladium-catalyzed reaction of an organotin compound 2 with a carbon electrophile 1 is called Stille coupling. 

As in case of other palladium-catalyzed reactions, the general mechanism of the Stille reaction is best described by a catalytic cycle—e.g. steps a) to c)  

Oxidative addition—Reaction of the carbon electrophile with palladium-(0) complex 5 to give a palladium-(II) complex 6. 

The palladium component may be added to the reaction mixture as Pd(0)- as well as Pd(ll)- compound in the latter case the Pd(ll)- first has to be reduced to Pd(0)- by excess stannane. Since the first publication on this coupling method by Stille in 1978, this reaction has gained increased importance in synthetic organic chemistry. This is due to the fact that many different types of substrates can be used in this reaction. The following table lists possible carbon electrophiles and stannanes that can be coupled in any combination. 

---

The mechanism " of the Suzuki reaction is closely related to that of the Stille coupling reaction, and is also best described by a catalytic cycle ... 

The Stille coupling reaction is very versatile with respect to the functionality that can be carried in both the halide and the tin reagent. Groups such as ester, nitrile, nitro, cyano, and formyl can be present, which permits applications involving masked functionality. For example, when the coupling reaction is applied to l-alkoxy-2-butenylstannanes, the double-bond shift leads to a vinyl ether that can be hydrolyzed to an aldehyde. 

Compounds 575, obtained by the Stille coupling reaction, react with PTAD to give high yields of the Diels-Alder products 576 obtained with good to excellent asymmetric induction (Equation 81) <1995SL1264>. 

The efficiency of fluorous Stille coupling reactions [5 a] is enhanced by use of microwave irradiation (Scheme 8.2). The reaction proceeds in 79% yield after 2 min with DMF as the microwave-active solvent. 

Wong reported that stoichiometric amounts of copper(I) chloride alone can promote the intramolecular Stille coupling (equation 138)243. In fact, copper(I)-mediated reaction was cleaner and faster compared with that catalysed by Pd(0) species. Selected examples of intermolecular Stille coupling reactions leading to dienes (Table 25)236a,242b 244, polyenes (Table 26)245 and macrocyclizations (Table 27)246 are given in the respective tables. 

TABLE 25. Synthesis of dienes through a Stille coupling reaction... 

The stereoselective synthesis of the 12-acetoxy enone 428, related to the limonoid azadiradione, has been achieved in 12 steps (16% overall yield), starting from tricyclic diester 429. The key steps involve an intramolecular 1,3-dipolar cycloaddition of a nitrile oxide and a Stille coupling reaction of vinyl iodide with stannylfuran (469). 

Oxazole compounds can also be produced by use of the Stille reaction. Clapham and Sutherland describe the use of tri-2-furylphosphine/Pd2(dba)3-catalyzed Stille coupling reactions (Scheme 12) to produce a range of oxazole-containing derivatives, including 58, with an 85% yield [56]. 

Dubac has employed a Stille coupling reaction to synthesize the pyrroles 88 and 89 from stannylpyrrole aldehyde 87 [71]. The latter tin compound was prepared as shown, and related stannylpyrroles were synthesized similarly [72] or using Muchowski s 6-dimethylamino-l-azafulvene dimer lithiation methodology [73]. 

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]. 

Table 1 Suzuki/Stille coupling reaction yield (direct coupling vs. two-step procedure)...

In organic synthetic procedures, alkenyltin compounds are often prepared with a view to subsequent transmetalla-tion with lithium, or to the Stille coupling reaction with a palladium catalyst (Equations (70) and (71)). 

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. 

In 1994, Badone et al. reported that the Stille coupling of allenylstannane 77 and aryl triflates 78 resulted in formation of various aryl-substituted allenes 79 in moderate to good yield (Scheme 14.18) [39]. The choice of catalyst was certainly a crucial issue in this process for optimizing yield and rate. The best results could be obtained employing a catalyst cocktail of Pd2(dba)3-TFP-LiCl-CuI. Similar Stille coupling reactions with stannylated allenes and aromatic iodides as substrates were described by Aidhen and Braslau [40a] and Huang et al. [40b],... 

However, in the absence of the copper cofactor, standard Suzuki or Stille coupling reactions prevailed, with selective replacement of the bromine rather than the methylthio group occurring to give 5-aryl derivatives 267 <2003OL4349>. 

The 5-methyl-2(37f)-oxazolone sulfonamide derivatives 265 are obtained from the sulfonamides 263 via bromination and subsequent Stille coupling reaction with tetramethyltin in the presence of palladium catalyst (Fig. 5.64). °... 

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. 

The Stille coupling reaction has been performed in l-bntyl-3-methylimidazolium tetrafluoroborate. Use of this solvent system allows for facile recycling of the solvent and catalyst system, which can be used at least five times with little loss in activity. An interesting preference in starting catalyst oxidation state for nse with aryl bromides and aryl iodides was observed (Handy and Zhang, 2001). 

In another example 2,5-bis(tributylstannyl)-furane was converted into 2,5-diarylfuranes in a double Stille coupling. Reaction with 4-bromo-benzonitrile, for example, give 2,5-bis(4 -cyanophenyl)-furane in good yield (6.31.)41... 

---