The cross-coupling reaction Ar-X + Nu -f Ar-Nu + X -, catalyzed by Pd(0) complexes, was studied theoretically by means of DFT calculations; Ph-Cl was used as a substrate and HS -as the nucleophile. The studied catalysts are the pristine Pd(0) complexes Pd 0 -(PR 3 ) 2 (1 R ; R ) H, vinyl, Ph), the corresponding anionic complexes Pd 0 (PR 3 ) 2 Cl -(1 R,Cl ), proposed by two of us (C.A. and A.J.), and the chelated complexes with diphosphine ligands PH 2 (CH 2 ) n PH 2 (2 H,n ; n ) 2-6). The full catalytic cycles were studied for 1 H , 1 H,Cl , 2 H,3 , and 2 H,6 . The efficiency of a catalytic cycle under turnover conditions is determined by the energetic span, the energy difference between the summit and trough of the cycle; the smaller the energy span, the higher the turnover frequency of the cycle. In this sense, the best Pd(0) catalyst was found to be the anionic 1 H,Cl species. The DFT analysis shows that the anionic catalyst so formed is superior to the pristine species, since it "flattens" the energy landscape of the catalytic cycle by stabilizing the transition state for oxidative addition, the summit of the cycle, and at the same time "destabilizing" the nucleophilic addition product, the deepest point of the cycle. This is precisely the role deduced initially from experimental evidence. Thus, during substrate activation, the Cl -ion keeps a small P-Pd-P angle, which is a prerequisite for a low activation barrier to oxidative addition. During nucleophilic substitution, the Cl -additive is displaced by the nucleophile, and hence the stabilizing advantage is lost, thereby raising the substitution product complex relative to the onset of the reactants. After product release, Cl -returns to regenerate the anionic catalyst, Pd 0 (PR 3 ) 2 Cl -, which in turn binds the substrate and prevents its diffusive escape, thereby ensuring an efficient restart of the cycle.

A Pd0 complex is spontaneously generated from Pd(OAc)2 and a bidentate phosphine such as dppp (1,3-bis(diphenylphosphino)propane). dppp is the reducing agent and is oxidized to the hemioxide dppp(O). The intramolecular reduction step is reversible. A stable Pd0 complex is quantitatively formed in the presence of 2 equiv of dppp, water, and a base (NEt3). The oxidative addition of PhI gives a cationic complex, PhPd(dppp)(dppp(O))+, in which dppp(O) behaves as a monodentate ligand. PhPd(OAc)(dppp) is formed in the presence of added AcO-. The oxidative addition of PhI is an intricate reaction whose kinetics has been investigated only in the presence of added AcO-. It involves reactive dimeric or/and monomeric Pd0 complexes ligated by AcO- whose relative reactivity is a function of the PhI concentration.

Two main intermediate complexes, PhPd(OAc)(dppp) and PhPdI(dppp), are generated in palladiumcatalyzed Heck reactions performed from PhI and an acetate salt used as a base, in DMF. Both complexes react with the electron-rich alkene isobutyl vinyl ether (CH 2 dCHO i Bu) exclusively by an ionic mechanism, i.e., via the cationic complex [PhPd(dppp)(DMF)] + formed by dissociation of AcOor Ifrom the parent complexes, as already established for the reaction of PhPd(OAc)(dppp) with styrene and methyl acrylate and the reaction of PhPdI(dppp) with styrene. A mechanism is proposed which rationalizes the regioselectivity observed when reacting the electron-rich isobutylvinyl ether in palladium-catalyzed Heck reactions.

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In DMF, the oxidative addition of PhI to Pd0(PPh3)4 or to the anionic Pd0(PPh3)3(OAc)- is slower in the presence of an alkene (styrene, methyl acrylate). Indeed, the concentration of the reactive Pd0(PPh3)2 or Pd0(PPh3)2(OAc)- complex decreases because of its coordination to the alkene to form the unreactive (η 2-CH2CHR)Pd0(PPh3)2 (R = Ph, CO2Me) or (η 2-CH2CHPh)Pd0(PPh3)2(OAc)-, respectively. As already evidenced in palladium-catalyzed Stille reactions, this work establishes that, in palladium-catalyzed Heck reactions as well, the nucleophile plays a role in the kinetics of the oxidative addition (decelerating effect), as soon as it may coordinate Pd0 complexes. This is an essential observation, in view of the general belief that the nucleophile enters the catalytic cycle only at the stage of the attack on the aryl−PdII complex formed in the oxidative addition. Whenever the oxidative addition is not rate determining, the decelerating effect of the alkene on this reaction is in favor of a higher efficiency of the catalytic cycle.

The mechanism of the reaction of secondary amines (piperidine, morpholine) with the cationic complexes [(η 3-PhCHCHCHR)PdL2]+BF4 - (R = Ph, L = PPh3 or L2 = dppb; R = H, L2 = dppb) has been investigated in DMF. The reaction, which affords the tertiary allylic amine, is irreversible when L is a monodentate ligand such as PPh3, whereas the reaction is reversible when L2 is a bidentate ligand such as dppb. In all cases, piperidine is more reactive than morpholine. The rate and equilibrium constants have been determined in DMF. These results can be combined with our previous results on the mechanism of the reversible formation of cationic [(η 3-PhCHCHCHPh)PdL2]+AcO- by reacting Pd0L2 complexes with (E)-PhCHCHCH(Ph)OAc. Fully established catalytic cycles are now proposed for the Pd-catalyzed allylic amination of (E)-PhCHCHCH(Ph)OAc by piperidine and morpholine. The amine and AcO- are in competition in their reaction with the cationic complexes [(η 3-PhCHCHCHPh)PdL2]+. The nucleophilic attack of the amine may be faster than the attack of AcO- and thus limited by the ionization step in which [(η 3-PhCHCHCHPh)PdL2]+ is formed, this ionization step being turnover limiting for the catalytic cycle.

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