Stille palladacycle

The stereochemistry of oxidative addition to the palladium(II) palladacycle was studied by Lautens using an enantioenriched secondary alkyl halide (Scheme 9) [32], From alkyl halide 23, product 24 was obtained, showing a net inversion of stereochemistry [33-35], Previous work by Stille showed that reductive elimination from palladium(IV) occurs with retention of stereochemistry [36], suggesting that oxidative addition occurs with an inversion of stereochemistry. This corresponds with the generally accepted SN2 mechanism for the reaction of palladium(O) with alkyl halides [37, 38],... 

Other palladium-catalyzed 1,5-C-H activation processes reported are extensions of known work. In these examples, palladium activates the C-H bond, but whether the migration occurs or not is still debatable. An aryl to imidoyl C-H activation takes place in substrate 28 (7) under the same reaction conditions that promote the 1,4-palladium migration. However, this reaction affords a much lower yield (compare with Scheme 10), which implies a relatively low efficiency for this 1,5-C-H activation. Mechanistically, the reaction can either go through a direct C-H activation to form a six-membered palladacycle, followed by reductive elimination, or a proton channeling-based palladium migration, followed by an arylation with the original aromatic ring. The exact path has not been established experimentally or computationally. 

Palladium Catalysts Yu s group has carried out systematic studies on Pd-catalyzed alkylations of aryl C—H bonds. Stille-type cross-coupling reactions have been developed by directed C—H activation (Equation 11.30) [68]. The reaction rate is enhanced by benzoquinone and microwave irradiation. Significantly, carboxylic acid functionality can be used as an efficient directing group for aryl C— H bond activation (Equation 11.31) [69]. The reaction conditions can be applied to the carboxylation of vinyl C— H bonds. The possible intermediacy of a palladacycle has been confirmed by NMR spectra and X-ray crystallography. 

Coupling reactions. Various (Heck, Stille, Suzuki, Sonogashira, and Ullmann) coupling reactions are mediated by a stable palladacycle 1. ... 

Palladacycles have also been used extensively as catalysts in other C—C bond forming reactions such as the Suzuki, Sonogashira and Stille couplings. Particularly active in this fleld are the groups of Bedford [107] and Najera (Fig. 10.13) [127, 128]. Usually these catalysts perform better in the presence of Bu4NBr. Surprisingly, much less mechanistic work has been performed in this area. 

Other examples include the use of palladacycles in the Stille reaction [110, 131,... 

At this point, there are still some gaps in our understanding, particularly concerning the reaction on chloroarenes where palladacycles seem to perform better than Pd(OAc)2, with or without added TBAB. This is unexpected if one assumes that both mechanisms proceed though a Pd(0)/Pd(ll) mechanism in which the Pd(0) is in the form of palladium nanoparticles. 

P,C-palladacycle precursors and ligated to the monophosphine 11 (Scheme 1.44). Kinetic data are still missing for most steps of the catalytic cycle [63]. The oxidative addition of aryl bromides is probably not rate determining, since the rate of the overall reaction is highly dependent on the structure of the alkene, as evidenced by competitive reactions of two different alkenes with the same aryl bromide in the presence of 5 [55a]. However, the alkene might also favour the reductive elimination in the palladacycle 5, which slowly delivers the active Pd(0) complex into the catalytic cycle [60]. 

Figure 6.1 Palladacycles applied in Stille coupling reactions.

Although this methodology constitutes an improvement on those previously reported, turnover frequencies were still generally <10 h, and hence there is considerable room for further improvement. Attempts to replace either pyridine by triethylamine [79], or Pd(OAc)2 by palladacycles [80], resulted in lower activities. 

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