Arene Stille reaction

A convenient method for preparing vinylated or arylated pyridines on insoluble supports is palladium-mediated cross-coupling. The Heck, Suzuki, and Stille reactions have been successfully used for this purpose (Table 15.22). The conditions are essentially the same as those used for the related coupling of arenes (see Section 5.4). 

The imidazole, benzoxazole, and benzthiazole derivatives in Table 7-3 are rather moisture-sensitive.92 On the whole, however, the heteroarylstannanes show the same reactions that characterise the homoarylstannanes. With a palladium catalyst, they undergo coupling112 and cross-coupling reactions68 and indeed much of the recent interest in the heteroarylstannanes stems from their applications in the Stille reaction (see Section 22.2). One aspect of this is the synthesis of oligomers and polymers or copolymers, for example by the cross-coupling of 2,5-distannylthiophene with a 1,4-diiodo-arene.113,114... 

Many heteroatom-centered nucleophiles can be arylated by the SrnI mechanism. For example, Ar-Cl and NMesAr react with MesSn" in liquid ammonia to provide the corresponding stannylated arenes in high yields [16,17]. Di- and tri-stannylated aromatic compounds can be prepared using di- and tri-chlorobenzenes as radical precursors [16]. The fact that Ar-Cl reacts easily with MesSn" by SsNl-typs chemistry and that Ar-1 bonds are much more reactive than Ar-Cl bonds in the Stille reaction allowed for the development of an attractive iterative approach to the synthesis of poly-aryl compounds, as shown in Scheme 13.2. 

The total hydrogenation of benzene derivatives represents an important industrial catalytic transformation, in particular with the conversion of benzene into cyclohexane, a key intermediate in adipic acid synthesis, which is used in the production of Nylon-6,6 (Scheme 1). This reaction is still the most important industrial hydrogenation reaction of monocyclic arenes [1]. 

Polymer formation is still observed with some sterically hindered thiolates, 2,4,6-Ao-propyl thiophenolate, and 2,4,6-trimethyl thiophenolate complexes have been studied. They can be synthesized by the reaction of Zn[N(SiMe3)2]2 with the appropriate arene chalcogenol. With the least steric bulk, the trimethyl derivative forms coordination polymers that can only be dissolved in strongly coordinating solvents. The iso-propyl derivative is more soluble forming oligomers in solution. 1... 

The development of ferrocene 9 was part of our studies on planar-chiral compounds, which also involved the synthesis of other scaffolds such as chromium-tricarbonyl arenes [15], sulfoximidoyl ferrocenes [16], and [2.2]paracyclophanes [17]. In aryl transfer reactions, however, ferrocene 9 proved to be the best catalyst in this series, and it is still used extensively today. 

The arylation of support-bound arenes has mainly been performed using the Suzuki and Stille coupling reactions. Both reactions proceed smoothly with arenes and het-eroarenes such as furans, thiophenes, or pyridines. Examples of the arylation of het-eroarenes are presented in Chapter 15. 

Biaryls have also been prepared by coupling support-bound aryl halides with aryl-zinc compounds (Figure 5.20) or with aryl(fluoro)silanes [203]. As with Suzuki or Stille couplings, these reactions also require transition metal catalysis. An additional strategy for coupling arenes on solid phase is the oxidative dimerization of phenols (Figure 5.20). 

A catalytic arene-arene coupling can occur in the presence of cooxidants such as Cu11, Fe111 and heteropolyacids along with molecular oxygen, but this reaction is still not selective enough for industrial use. 

Systems based solely on amidic functions are still relatively rare in the cal-ixarene literature. One of the earliest examples is based on chlorosulphonation of calix[4]arene and subsequent reaction with alkylamines, which leads to the corresponding sulphonamides 27a-d. 

The one-pot Stille cross-coupling reaction of compound 256 produced all four isomeric thieno[3,2-c]naphthyridines (1994JHC11). The stepwise formation of the C(7)-C(7a) and C(4)-N(5) bonds of the thieno[3,2-c]pyridine system can be considered as a modification of the above-described approaches. For example, aldehyde 256 reacts with arene 265 to give 266 reduction of its nitro group is accompanied by cyclization to form thieno[3,2-c]isoquinoline A-oxide (267) (1990JHC1127). 

Classical Friedel-Crafts catalysts such as BF3 etherate or Bronstedt acids, which are applied in stoichiometric amounts or even in excess, still have their value, because they are relatively inexpensive yet powerful catalysts for C-H transformation at arenes and, most importantly, they are often successful when modern catalysts fail. Gold(III) chloride, at less than 1 %, has impressive reactivity under very moderate reaction conditions and its selectivity is exceptionally good. Friedel-Crafts type reactions with this catalyst are, however, restricted to very electron-rich arenes. Further studies should concentrate on increasing the electrophilicity of gold catalysts. New catalysts have emerged, for instance based on ruthenium and rhenium, which promise broad applicability based on alternative mechanisms. Catalysts based on rare earth metals are discussed in the next chapter. 

In a recent review it was argued that such additives of copper, benzoquinone, and HPMOV are not really needed all that is needed is the presence of oxidation-resistant ligands that prevent palladium metal formation [15]. Indeed, activation of the C-H bond is not as slow as, for example, the Wacker reaction of ethene in which reoxidation of palladium must be performed by copper oxidation, although in this catalytic system the additives may still play a role in stabilizing the intermediate low-valent palladium species and thus prevent catalyst decomposition. This thesis was corroborated by the work of de Vos and Jacobs, who showed that addition of benzoic acid to the oxidative arylation reaction in the presence of oxygen led to superior results in the coupling of a variety of substituted arenes with acrylates, cinnamates, and ,/f-unsaturated ketones. Very good yields and TON up to 762 were obtained at 90 °C. A mixture of the o, m, and p isomers is obtained if substituted arenes are used [16]. 

Desymmetrisation by enantioselective ortholithiation has been achieved with ferrocenylcarboxamides 434,187 and also (with chiral lithium amide bases) a number of chromium-arene complexes.188 The chromium arene complex 435, on treatment with s-BuLi-(-)-sparteine, gives 436 enantioselectively, and reaction with electrophiles leads to 437. However, further treatment with r-BuLi generates the doubly lithiated species 438, in which the new organolithium centre is more reactive than the old, which still carries the (-)-sparteine ligand. Reaction of 438 with an electrophile followed by protonation therefore gives ent-431.m... 

While more than a decade has passed since the first reports of reactions with i/2-bound aromatic molecules, this field is still in its infancy compared to the more established field of rj6-arene chemistry. Nevertheless, the general strategy of using a transition metal to render a conjugated re-system more electron-rich is now firmly established. The next phase of development will be marked by a greater focus on practical issues such as less expensive re-basic metal systems, effident control of absolute stereochemistry, and standardization of procedures that allow for easier reagent handling. 

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