Ligand effects Stille coupling

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 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... 

One difference between the Suzuki mechanism and that of the Stille Coupling is that the boronic acid must be activated, for example with base. This activation of the boron atom enhances the polarisation of the organic ligand, and facilitates transmetallation. If starting materials are substituted with base labile groups (for example esters), powdered KF effects this activation while leaving base labile groups unaffected. 

An air and moisture stable, low-coordinate phosphine ligand has been found to be effective in the Stille coupling of pyridine derivatives. This was exemplified in the transformation of 136 to 169 [85]. 

Caminade and Majoral reacted phosphorus-containing dendrimers with various transition metal complexes (Fig. 7) [ 113 ]. Via phosphane, diphosphane, or P=N-P=S ligands, they were able to incorporate several metals (Pd, Pt, Rh, Au, Fe, W, Zr) either in the core or in the periphery of their dendrimers. The dendritic palladium and ruthenium complexes 7 have been introduced in Stille couplings, Knoevenagel condensations and diastereoselective Michael additions. A positive dendritic effect and high stability of dendritic Pd complexes has been observed. Separation occurred by precipitation with ether and reuse was reported. 

In the initial study, which focused on palladium-catalyzed cross-couplings of primary alkyl bromides with vinylstannanes, use of P(t-Bu)2Me provided the best yields (solvent=THF) [27]. PCy3 was slightly less effective, whereas a variety of other ligands, including JV-heterocyclic carbenes, were essentially ineffective. The choice of activator (Me4NF) and the presence of molecular sieves were important for the success of these reactions. Some examples of Pd/P(t-Bu)2Me-catalyzed Stille couplings of alkyl bromides with vinylstannanes are provided in entries 1-3 of Table 6. 

Weber and coworkers reported catalyst screening of the Stille coupling reaction using a capillary microreactor (75 pm i.d., 6.7 m length) [17]. Optimum palladium catalysts and ligands were screened effectively by the flow regime, where the reaction products were analyzed by on-line gas chromatography. 

In some synthetic applications, specific bases such as Cs2C03 or TIOH have been found preferable to NaOH. Conditions for effecting Suzuki coupling in the absence of phosphine ligands have been developed. One of the potential advantages of the Suzuki reaction, especially when boronic acids are used, is that the by-product boric acid is more innocuous than the tin by-products generated in Stille-type couplings. 

Table 1 Effect of the Ligand on the Stille Coupling of an Alkyl Bromide...

It is reported in literature that additives like LiCl or Cu(I) salts can have a dramatic influence on the coupling. The copper effect in Stille coupling reactions was investigated by Farina and Liebeskind and coworkers. For instance in the reaction of iodobenzene and vinyltributyltin in dioxane at 50 °C catalyzed by Pd2(dba)3 in presence of a strong ligand like PPhs, it was found that the addition of 2 molar equivalents of Cul per mol of catalyst led to a > 100 fold increase in reaction rate. 

The classification of 5-HT-receptors is still an ongoing field of research. 5-HTi, 5-HT2, 5-HT4, 5-HTe and S-HT subtypes belong to the superfamily of G-protein coupled receptors whereas the 5-HT3 subtype is a ligand-gated ion channel. The activation of 5-HTi-receptors induces excitatory or inhibitory effects in the periphery as well as in the central nervous system. There are presynaptic 5-HTi-autoreceptors. 5-HT2-receptors in the periphery are located postsynaptieally, their stimulation induce only excitatory effects. 

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