Protocols ligand-accelerated

We should stress that this difference only applies to processes in which palladium species have an undefined coordination shell (as in type 1 and type 2 systems). For true ligand-accelerated type 3 processes, which are controlled by a definite stable Ugand in the coordination shell, the difference between electron-rich and electron-poor ( inactivated versus activated ) substrates is indeed not dramatic, which allows for the formulation of broad-scope robust protocols. 

Historically, this distinction was first made by Heck on the basis of two different systems, one based on a simple palladium salt for aryl iodides [2] and another based on the PhsP or (2-tolyl)3P complex of palladium for aryl bromides [6-8]. However, as the performance of these initial systems was far from the levels achieved later, we cannot conclude for sure that a ligand-accelerating effect is observed in these protocols. We know today that aryl iodides and reactive aryl bromides are highly reactive practically with any form of labile palladium complex, so that the ligand-accelerating effect cannot be reliably established for these substrates in the many published protocols (type 1 and type 2 systems). 

Despite electron-rich bulky side-arms as in phosphine pincers 190,191 [245] or 192 [246] (Figure 2.24), these complexes behave strikingly different from their respective dialkyl or trialkylphosphine palladium complexes the latter complexes show t)q)e3 activtity (cf. Hartwig-Fu protocol see above). PCP-pincer complexes 190-192, however, are typical SRPCs exclusively suitable for type 1 reactions of aryl iodides and activated aryl bromides (Table 2.9, entries 1-6). Ligand-acceleration effects are not observed, which unequivocally underlines that the cleavage of these pincer complexes under the reacation conditions occurs to release nonphosphine palladium complexes with indeterminate coordination shell. 

In another protocol using a ruthenium(pyridinebisoxazoline)(pyridinedicarboxylic acid) catalyst 26 and iodosylbenzene as the terminal oxidant, Seller and co-workers <03TL7479> found that the addition of water and protic solvents resulted in a 100-fold acceleration of the epoxidation, presumably due to a ligand dissociation effect that promotes the oxidation of the ruthenium catalyst. Thus, the conversion of rrans-stilbene 27 to the corresponding 5,S-epoxide 28 required 96 h in anhydrous toluene, but only 1 h in the presence of r-butanol and water. The enantioselectivity of the reaction was not significantly affected (63% and 57% ee, respectively). 

In conjunction with soft ligands such as AsPhs, the copper salt can accelerate the rate of cross coupling drastically in conventional Stille coupling protocol. These improved coupling conditions have been applied to the total s)Tithesis of guanacastepenes A, E, and of (—)-Gambierol, wherein the coupling of a (Z)-vinyl bromide or allyl acetate with a vinyl stannane or silane was achieved in excellent yield (eqs 22 and 23). 

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