Ligand effects Suzuki coupling reactions

Phosphine 23 proved in general to be an excellent ligand for Suzuki coupling reactions to form stericaUy hindered tetra-ortho-substituted biaryls in good yields. Ortho substituents such as methyl, primary alkyl, phenyl, and alkoxy groups are accommodated. It was necessary to use 2.0 equiv of the boronic acid to effect complete consumption of the aryl bromide in some cases, presumably due to competitive pro-todeboronation. Crystallographic analysis of 23/Pd(dba) revealed an unusual rc-coor-dination of the phenanthrene moiety - the first of its type for a Pd(0) complex (Equation 50) [61]. 

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. 

The Suzuki reaction has already found a first industrial application [24], after the catalyst Pd(TPPTS)a n HaO became available [25], In a two-phase procedure, the water-soluble catalyst effects the C-C coupling of arylboronic acis with aryl chlorides to form pharmaceutical intermediates. The Suzuki C-C cross-coupling is on the way to industrial perfection. Since the basic mechanistic features are clear by now, it is desirable that the catalysts are easy to prepare, easy to handle, and cheap, and that they bear cr-donor type ligands of which at least one does not dissociate from the metal throughout the catalytic cycle. Thus the Suzuki coupling will be seen in the syntheses of a growing number of fine chemicals and pharmaceuticals in due course. 

Pd-catalyzed C-C-coupling reactions of the Heck type, e. g., Suzuki [48c] and Stille [49c] cross-coupling, are excellent tools for the preparation of biaryls (see also Section 3.1.9). The activity and stability of the catalyst is highly dependent on the steric and electronic properties of the ligands. Sterically demanding basic alkylphosphines e. g., tri(/-butyl)phosphine, have proven to be very effective ligands in the Heck reaction [50] as well as in the Suzuki cross-coupling [51]. NHCs resemble those basic phosphines (see above) and therefore were tested... 

Although side reactions associated with the supporting phospine ligands do not greatly affect small molecule couplings, they can affect polymerizations dramatically. The effect of one of these side reactions will be discussed. A general catalytic cycle for the Suzuki coupling process is shown in Scheme 1. 

A convenient and effective palladium-catalysed Suzuki-Miyaura cross coupling reaction of deactivated aryl chlorides with phenylboronic acid utilised the 1,3-diazepinium salts 107 as in situ precursors of the palladium ligands. These salts were prepared from the diamines 106 and cyclocondensation with triethyl orthoformate <05SL2394>. 

The Suzuki cross-coupling methods described in Sect. 2.1 establish that palladium complexes that bear electron-rich trialkylphosphines of the appropriate size can serve as effective catalysts for reactions of alkyl electrophiles. Naturally, it was of interest to determine if non-phosphine ligands that are bulky and electron-rich can also furnish active catalysts. 

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