Palladium-catalyzed cross-coupling reductive elimination

The palladium-catalyzed cross-coupling of an aryl, alkenyl, or benzylzinc bromide 11 with aryl iodide 12 succeeds with 0.15 mol-% [Pd P(C6H4C6Fi3)3 4] in toluene/1-bromoperfluorooctane, taking advantage of variable miscibility through thermoregulation [20], In this case the electron-deficiency of the phosphanes, due to the perfluorinated side chains, appears to influence the reductive elimination step in the cross-coupling reactions. 

The mechanism of the Sonogashira reaction has not yet been established clearly. This statement, made in a 2004 publication by Amatore, Jutand and co-workers, certainly holds much truth [10], Nonetheless, the general outline of the mechanism is known, and involves a sequence of oxidative addition, transmetalation, and reductive elimination, which are common to palladium-catalyzed cross-coupling reactions [6b]. In-depth knowledge of the mechanism, however, is not yet available and, in particular, the precise role of the copper co-catalyst and the structure of the catalytically active species remain uncertain [11, 12], The mechanism displayed in Scheme 2 includes the catalytic cycle itself, the preactivation step and the copper mediated transfer of acetylide to the Pd complex and is based on proposals already made in the early publications of Sonogashira [6b]. 

Palladium and platinum form numerous alkyl complexes of the types M(R)(X)L2 and MR2L2, usually stabilized by phosphine ligands. The palladium compounds are prone to reductive elimination this is important in palladium catalyzed cross-coupling reactions (Section 21-14) ... 

The mechanism for this palladium-catalyzed cross-coupling reaction comprises the initial oxidative addition of the electrophile 37 to the palladium(O) catalyst followed by transmetallation of triethylsilane to yield the corresponding bis(organo)palladium(II) complex 39, which then undergoes reductive elimination to form the alkene 40 and to regenerate the palladium(O) catalyst. 

Reductive elimination of the unsymmetrical complexes is assumed to be the product-forming step in palladium-catalyzed cross-coupling reactions of organic halides... 

The generally accepted catalytic cycle for the Buchwald-Hartwig amination mirrors that of other palladium catalyzed cross-coupling reactions.10 11 irThere is an oxidative addition (A to B), followed by an exchange on palladium (B to C), and finally a reductive elimination (C to D and A). The main difference involves the exchange step. In a Suzuki, or Stille, reaction this step proceeds through a discrete transmetallation event, whereas... 

The final step in Scheme 69 is similar to that suggested for nickel or palladium-catalyzed cross-coupling of terminal alkynes with chlorophosphines to give phos-phinoalkynes. After P-Cl oxidative addition, Sonogashira-style formation of a metal-alkynyl group and P-C reductive elimination were proposed [123, 124]. 

The mechanism of the direct intramolecular Buchwald-Hartwig indole synthesis is that of a traditional palladium-catalyzed cross-coupling reaction and begins with loss of a ligand on palladium. Oxidative addition of an appropriately substituted Z-vinylhaloarene (1) generates intermediate 2. Deprotonation of 2 and displacement of a halide ligand sets up a reductive elimination on 3 to yield indole 4. 

On the other hand, for a series of [Pd(L-L)Me2] with L-L = dppp (bis(l,3-diphenylphosphino)propane), dppf, and dppr (l,l -bis(diphenylphosphino)ruthe-nocene), the fastest elimination was observed for the ligand with the largest bite angle [357, 358]. This effect on the reductive elimination was also found by Hayashi et al. [359] and van Leeuwen [360] in the palladium-catalyzed cross-coupling reaction of Grignard reagents with aryl halides. 

Palladium-catalyzed cross-coupling reactions of allylic electrophiles with allylic metals seem to constitute an appropriate approach to 1,5-hexadienes. However, the allylation often suffers from low yields because of slow reductive elimination from the fairly stable diallylpalladium intermediates. This is also the case even when homoallylic alcohols are used instead of allylic metals. In the specific case in Scheme 5.33, branched-coupling product was obtained in low yield along with -methylstyrene as the major product, which underscores the difficulty in achieving efficient synthesis of 1,5-hexadienes. 

The palladium(0)-catalyzed cross-coupling of alkenyl or aryl halides and triflates with organometallics proceeds via sequential oxidative addition (to species A below), transmetalation (usually rate determining), isomerization, and reductive elimination processes. The catalysts commonly used are the Pd(0)-complexes Pd(PPh3)4 or Pd2(dba)3. 

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