Arylstannanes Stille coupling

The scope and limitations of Pd(0)-mediated coupling reactions between aromatic halides linked to a polystyrene resin and boronic acid derivatives (Suzuki coupling) or arylstannanes (Stille coupling) have been reported. For all the reactions, the conditions were optimized and evaluated with various reagents. In most cases, products were obtained in excellent yields upon cleavage from the solid support (Eq. (63)) [101]. 

Innumerable aryl- and heteroarylstannanes take part in Stille couplings with halopyridines. In one such example, the union of arylstannane 106 and 4-bromopyridine furnished arylpyridine 107 [90], Arylstannane 106 was prepared from the Pd-catalyzed reaction of hexabutylditin with iodoarene 105, which arose from aminobenzolactam 104 via a Sandmeyer reaction. 

The Stille coupling of 2-chloro-5-tributylstannylpyridine with an enantiopure 2-iodo-cyclohexenon (7.29.) derivative formed the basis of the total synthesis of (+)-epibatidine. The reaction is a nice example of the chemical inertness of arylstannanes and the mildness of the coupling conditions. Both the enone moiety and the chiral ally lie centre remained untouched in the process. The effective coupling required the use of a soft ligand, triphenylarsine and the addition of copper(I) iodide as co-catalyst.40... 

There are a number of commonly used reactions of this type and many are named after the chemists who discovered them. They differ, among other things, in the exact nature of the metallic component. One of the first to be developed extensively was the Stille coupling, which specifically involves the coupling of an arylstannane with an aryl halide or triflate under the action of palladium catalysis (Scheme 10.19). 

Arylstannanes reacted with 2-iodoimidazole under Stille conditions gave rise to cross-coupled products. The imidazole modified tetrathiafulvalene 362, synthesized via Stille coupling, formed a charge transfer complex with chloranil, which displayed metal like conductivity for the first time in a purely organic material (Scheme 85) <2004AGE6343>. 

Stille coupling. Arylstannanes in which the three other substinients on Sn are fluoroalkyl (e.g., CgFjjCHjCHj) have many attractive features for the coupling with halides. 

When 1,2-diiodoalkenes were subjected to the coupling reaction monofunctionalization occurred successfully and the new C-C bond was formed preferentially at the less hindered iodide [160]. Migita-Kosugi-Stille coupling occurs preferably at iodide and bromide leaving fluoride intact - treatment of fluoroethenyl iodide [161] and bromide [162] with arylstannane in the presence of palladium catalyst afforded the corresponding ethenyl fluoride products, respectively. 

Stille coupling. The many examples describing applications of this C-C bondforming method attest to its versatility. A comprehensive study of the coupling of arylstannanes with sulfonates has appeared. Of course, various combinations of aryl/aryl, aryl/vinyl, and vinyl/vinyl couplings are equally possible. PhsAs is often added to the reaction media, and in other cases Cul acts as a cocatalyst. 

Table 6 Stille couplings of alkyl bromides and iodides with vinyl- and arylstannanes...

Arylboronic acids undergo cross-coupling with vinyl halides or tri-flates imder conditions similar to biaryl coupling. The introduction of aryl moieties directly at the 2-position of carbapenum was first demonstrated by the Stille coupling of arylstannanes, but the procedure is being reinvestigated by Merck in USA because of the toxic by-products which are difficult to remove, especially in large-scale production (Eq. 69). ... 

Palladium-catalyzed cross coupling of resin bound iodopyridine with a boronic acid (Suzuki reaction) (12) or with an alkenyl-, alkynyl-, or arylstannane (Stille reaction) (13) was effected by treatment of resin 5 with 4 equivalents of the boronic acid or stannane, 8 equivalents of K2CO3 (Suzuki reaction only), and catalytic Pd(PPh3)4 in DMF at 50 C for 20 hours. (14) Best results were achieved by running each reaction twice, with an intermediate wash of the resin, in order to drive the reaction to conq>letion. The corresponding Pd-catalyzed amination (Buchwald reaction) (15) worked well in protocol development but the reaction failed with the 3 amines attenpted during actual library preparation. 

Diaryl ketones are important scaffolds in biologically active compoimds, and although several synthetic pathways are available in solution, their application in solid phase synthesis is rare. Yun et aL [85] have developed a high-throughput synthesis of diaryl ketones via a Stille carbonylation on solid phase. Immobilized arylstannanes 39 were subjected to Stille coupling with aryl halides in presence of carbon monoxide (Scheme 23). Not only did the reaction afford products of high yield and purity, but it was also tolerant towards most functional groups. 

Porco s pathway to complete the synthesis of (- )-kinamycin C (3) is shown in Scheme 3.8. The arylstannane 34 and the a-bromoenone 35 were efficiently coupled by a Stille reaction using tris(dibenzylideneacetone)dipalladium and triphenylarsine... 

Stille cross-coupling and reductive N-heteroannulation steps. lodination of 1033, followed by Stille cross-coupling of the corresponding iodo derivative 1034 with the arylstannane 1035, gave the annotation precursor 1036. Reductive N-heteroannula-tion of 1036 afforded the carbazolone 1001, which was previously (99) (see Scheme 5.143) used to prepare clausenalene (90) via a Wolff-Kishner reduction followed by aromatization (659) (Scheme 5.155). 

An early attempt to use the Stille reaction on solid support is detailed in a paper from 1994 by Deshpande.57 In this, an aryl iodide linked to Rink amide or Wang resin is coupled to a number of vinyl and one arylstannanes (Scheme 23). The protocol used only 5 mol % Pt dba and proceeded in typically 90% yield at 45°C. Interestingly, the reactions were simply left to stand (rather than being shaken) overnight. 

The first Stille reactions on halopyridazines were described by Draper and Bailey in 1995 [48]. They successfully coupled 6-substituted 3-iodopyridazincs (151) with arylstannanes in refluxing THF or DMF at 80°C using Pd(PPh3)2Cl2 as the precatalyst. 

The first application of arylstannanes was presented by Stille who demonstrated the transferability of an aryl group from tetraphenyltin [50]. This approach was generalised by the improved preparation of arylstannanes from trialkylstannanes and aryl halides followed by their Pd(0) catalysed coupling with aryl halides [51]. Similarly to aryl halides, aryl triflates also react with arylstannates to give biphenyls [52]. Electron-rich aryl triflates are especially suitable coupling reagents in the synthesis of unsymmetrical biaryls [53]. Symmetrical biaryls can be easily obtained by the reaction of an aryl triflate with 0.5 eg. of hexamethyldistannane. 

Two reports have described palladium-catalyzed Stille cross-couplings of unactivated alkyl electrophiles. Specifically, these investigations by Fu demonstrate that primary alkyl bromides and iodides can be coupled with vinylstannanes [27,28] and arylstannanes [28] (Eq. 10). 

Moreover, copper(l) halides or manganese(ll) bromide efficiently catalysed the Stille reaction of arylstannanes with aryl halides without any palladium catalyst added [87,88]. In contrast to MnBr2, manganese(II) chloride was proved as a less effective catalyst, whereas manganese(II) iodide-mediated reactions failed to give any cross-coupled products [88]. The latter achievements dramatically extend the economy of the Stille reaction since the use of, generally very expensive, palladium chemicals is completely avoided. 

The aryltrialkylstannanes obtained by above described methods affected the Stille cross-coupling reactions whose efficacy is presented through the following examples where arylstannanes 172-176 were reacted with aryl halides 25, 177, 178 and iodobenzene giving biaryls 179-183 in respective yields [77], Scheme 25. 

In 2003, when the second edition appeared, it was clear that the Stille chemistr/ had really come of age, as shown by the increasing number of applications of palladium-catalyzed cross-coupling reactions of vinyl- and arylstannanes in natural product synthesis and in advanced organic synthesis. In the past decade, these types of applications, of course, remained very important and, in addition, the use of allylstannanes in palladium-catalyzed coupling reactions received much attention. Cross-coupling of allylstannanes with imines also forwarded the area of asymmetric catalysis. 

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