Stille coupling aryl chlorides

The first example of a NHC-Pd catalysed Stille reaction between aryl bromides and aryl stannanes was reported by Herrmann in 1999 [120]. Summarised in Scheme 6.36 are the best results obtained when the weU-defined pre-catalyst 22 was employed. Unfortunately, the coupling of aryl chlorides was not possible. 

As Figure 16.7 reveals, an aryl iodide reacts more rapidly with an alkynylcopper compound than an aryl bromide. The palladium-catalyzed C,C coupling reactions, which will be discussed later in the present chapter, also proceed more rapidly with an aryl iodide than with an aryl bromide (example Suzuki coupling in Figure 16.22) or an aryl chloride (example Stille reaction in Figure 16.27). There are still some details that are not fully understood one is inclined to assume that in accordance with the Hammond postulate the weaker C-I bond (dissociation energy DE = 51 keal/mol) breaks more rapidly with the initial oxidative addition... 

The activity of this catalytic system was somewhat lower with aryl chlorides (yields were between 51 and 94%) but still it was better performing that previously reported systems [42-47]. Of note, this coupling could be carried out in THF instead of pyridine on the condition of using aryl iodides as starting materials [48]. 

The Stille coupling may be combined with carbonylation in two ways. Acid chlorides may be used as substrates for the reaction with vinyl or aryl stannanes. However, an atmosphere of carbon monoxide is frequently required to prevent decarbonylation after the oxidative addition step. 

The scope of the Heck and related coupling reactions was substantially broadened by the development, in the last few years, of palladium/ligand combinations which are effective with the cheap and readily available but less reactive aryl chlorides [86, 87] rather than the corresponding bromides or iodides. The process still generates one equivalent of chloride, however. Of interest in this context, therefore, is the report of a halide-free Heck reaction which employs an aromatic carboxylic anhydride as the arylating agent and requires no base or phosphine ligands [89]. 

Unlike other cross-coupling reactions, for which the scope has rapidly expanded in recent years, the range of electrophilic substrates that can be used successfully in the Sonogashira protocol is still rather limited. Vinylic substrates (iodides, bromides, chlorides, triflates, and more recently tosylates) typically yield the best results. For aromatic substrates, iodides and triflates are preferred over bromides, which in turn give far better yields than aryl chlorides. This latter aspect of the reaction is particularly frustrating when one considers the recent advances in the activation of aryl chloride substrates for reactivity in other cross-coupling protocols. ... 

The reactions have a very wide scope. Acyl halides serve as substrates for Stille couplings in addition to the usual aryl and alkenyl halides however, most alkyl halides cannot be used as substrates. Like Pd-catalyzed carbonylations, reactions proceed most quickly when X = I and rather slowly when X = Cl, although especially bulky phosphine ligands such as /-Bu3P allow even aryl chlorides to undergo coupling at room temperature. Again, triflates are also widely... 

Suzuki and Stille couplings. For coupling of aryl chlorides with arylboronic acids the catalytic system contains (CyjPjjPdClj, CsF in NMP. co-Arylalkanoic acids are prepared by coupling of aryl halides with carboxylic esters bearing a 9-BBN substituent at the other terminus, and saponification. A biaryl synthesis from two different aryl halides is accomplished with in situ boronate formation which depends on the (dppfjPdClj catalyst. For access to aryl boronates either the coupling of aryl triflates with bis(pinacolato)diboron" or that of aryl iodides with pinacolborane may be employed. 

Bedford and co-workers have demonstrated that palladium complexes of the simple, inexpensive tricyclohexylphosphine display very high activity in the Stille coupling of non-activated and deactivated aryl chlorides [Equation (5.3.6)]The use of K3PO4 is necessary to promote the coupling. 

The Stille coupling reaction is the most versatile method among all Pd-catalyzed crosscoupling reactions with organometallic reagents. By lithiation of 4-methyloxazole with H-BuLi and subsequent quenching with trimethyltin chloride, Dondoni et al. prepared 2-trimethylstannyl-4-methyloxazole [39], which was then coupled with aryl- and heteroaryl-halides to provide the expected 2-aryloxazole. Thus, 2-trimethylstannyl-4-methyloxazole was coupled with 3-bromo-pyridine to afford oxazolylpyridine 35. 

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