Acetoxypalladation

Palladium-catalyzed oxidation of 1,4-dienes has also been reported. Thus, Brown and Davidson28 obtained the 1,3-diacetate 25 from oxidation of 1,4-cyclohexadiene by ben-zoquinone in acetic acid with palladium acetate as the catalyst (Scheme 3). Presumably the reaction proceeds via acetoxypalladation-isomerization to give a rr-allyl intermediate, which subsequently undergoes nucleophilic attack by acetate. This principle, i.e. rearrangement of a (allyl)palladium complex, has been applied in nonoxidative palladium-catalyzed reactions of 1,4-dienes by Larock and coworkers29. Akermark and coworkers have demonstrated the stereochemistry of this process by the transformation of 1,4-cyclohexadiene to the ( r-allyl)palladium complex 26 by treatment... 

Based on a /rarcr-acetoxypalladation of the triple bond, Lu has developed a highly enantioselective (up to 87% ee) synthesis of 7-butyrolactones with Pd(n) catalysis (Scheme 73).280 Following the initial /ra/w-acetoxy-palladation, a plausible mechanism for this sequence involves an intramolecular carbopalladation of the pendant olefin, and deacetoxypalladation instead of the common /3-hydride elimination in the final step. 

Pyrroles and fiirans were prepared by the intramolecular carbon-carbon bond formation between pendant acetylene and nitrile or carbonyl functions. The process, running in acetic acid, starts by the fraw-acetoxypalladation of the acetylene moiety, which initiates a series of further transformations. The nature of the ring formed is determined by heteroatom bridging the two reactive units. The propargylamine derivative in 3.88., for example gave a pyrrole ring.112... 

The mechanism of vinyl acetate formation is closely related to that of the Wacker oxidation (Scheme 9.11) that is, acetoxypalladation-palladium hydride elimination takes place.498,503 The coordinated alkene is attacked by the external nucleophile acetate ion, or the attack may occur within the coordination sphere. p-Hydride elimination followed by dissociation of the coordinated molecule yields directly the vinyl acetate end product. 

These studies, plus analogy with other Pd(II) chemistry (3), leave little doubt that the general mechanism for these exchanges involves addition of acetate (acetoxypalladation) or chloride (chloropalladation) followed by elimination of acetate (deacetoxypalladation) or chloride... 

Further evidence that acetoxypalladation is stereospecific is provided by the fact that cyclic esters such as 1-cyclopenten-l-yl ester do not exchange. As shown by Equation 16, stereospecific addition—elimination would not permit exchange. 

Chloropalladation is somewhat different. Acetate does not attack cis because it is believed that chloride is much more strongly complexed to Pd(II) than acetate, and thus, acetate cannot get in the coordination sphere to attack cis. Chloride is already in the coordination sphere and thus in position for cis attack. Chloride might also be expected to attack trans from outside the coordination sphere as does acetate. For these reasons, chloropalladation may not be as stereospecific a process as acetoxypalladation in fact, this is the case. For example 1-chlorocyclo-... 

Very little work has been carried out on the kinetics of the PdCl2 only system. This is probably because of the slowness of the reaction. A stereochemical study using 3,3,6,6-cyclohexene-d4, however, provided evidence for frarw-acetoxypalladation in this system (5). For example the reaction scheme for formation of 3-cyclohexen-l-yl acetate is shown in Equation 22 (from Ref. 5). This scheme involves frans-acetoxypallada-tion and ci -Pd(II)-H (D) eliminations and additions. This agrees with the exchange kinetics which also suggest frarw-acetoxypalladation. 

Stereochemical studies were carried out using cis- and trans- 1-propen-1-yl propionate. It was found that each of these esters exchanged to give mixtures of cis- and trans- 1-propen-l-yl acetates. As shown by Equation 15, this result is unexpected if acetoxypalladation were a stereospecific process. Further evidence was provided by the fact that 1-cyclopen ten-1-yl propionate exchanged to give the corresponding acetate. Again, as shown by Equation 16, this result is unexpected if acetoxypalladation were stereospecific. 

The product distributions and their change with acetate concentration is also of interest. A study of the initial product distributions with various terminal and internal olefins provided strong evidence for an acetoxypalladation step followed by a Pd(II) hydride elimination (7). 

In the case of certain diolefins, the palladium-carbon sigma-bonded complexes can be isolated and the stereochemistry of the addition with a variety of nucleophiles is trans (4, 5, 6). The stereochemistry of the addition-elimination reactions in the case of the monoolefins, because of the instability of the intermediate sigma-bonded complex, is not clear. It has been argued (7, 8, 9) that the chelating diolefins are atypical, and the stereochemical results cannot be extended to monoolefins since approach of an external nucleophile from the cis side presents steric problems. The trans stereochemistry has also been attributed either to the inability of the chelating diolefins to rotate 90° from the position perpendicular to the square plane of the metal complex to a position which would favor cis addition by metal and a ligand attached to it (10), or to the fact that methanol (nucleophile) does not coordinate to the metal prior to addition (11). In the Wacker Process, the kinetics of oxidation of olefins suggest, but do not require, the cis hydroxypalladation of olefins (12,13,14). The acetoxypalladation of a simple monoolefin, cyclohexene, proceeds by trans addition (15, 16). 

A widely accepted mechanism for acetoxylation of ethylene is shown in equation (161) and consists of the nucleophilic attack of the acetate anion on the coordinated ethylene, followed by acetoxypalladation and /3-hydride elimination, giving vinyl acetate and palladium hydride.367... 

With higher alkenes, alkenyl acetates, allylic acetates and dioxygenated products are obtained [58], The reaction of propylene gives two propenyl acetates, 66 and 67, and allyl acetate (68) by the acetoxypalladation to form two intermediates, followed by elimination of /1-hydrogens. The chemoselective formation of 68 by a gas-phase... 

Palladium(II)-promoted oxidative 1,4-difunctionalization of conjugated dienes with various nucleophiles is a useful reaction [98], The reaction is stoichiometric with respect to Pd(II) salts, but it can be made catalytic by use of Pd(0) reoxidants. 1,4-Difunctionalization with the same or different nucleophiles has wide synthetic application. The oxidative diacetoxylation of butadiene with Pd(OAc)2 proceeds by acetoxypalladation to generate the 7i-allylpalladium 136, which is attacked by acetoxy anion as the nucleophile, and (E)-, 4-diacctoxy-2-butcnc (137) is formed with 3,4-diacetoxy-1-butene (138) as the minor product. The commercial process for 1,4-diacetoxy-2-butene (137) by the reaction of butadiene, AcOH and O2 has been developed using a supported Pd catalyst containing Te. 1,4-Butanediol (139) and THF are produced commercially from l,4-diacetoxy-2-butene (137) [99]. 

The synthesis of five-membered carbo- and hetero-cyclic compounds, including fused rings, has been reported using acetate as a nucleophile in the cyclization of 1,6-enynes under palladium(II) catalysis (Scheme 91). The reaction is initiated by trans-acetoxypalladation of the alkynes and quenched by either trans- or ra-deaceloxypal-ladation in the presence of 2,2/-bipyridine as the ligand.134... 

The vinyl acetate is almost certainly formed by acetoxypalladation followed by Pd(II)-hydride elimination ... 

The homoallylic acetate contained all the deuteriums initially present in the deuterated cyclohexene. One of the deuteriums had been stereo-specifically transferred to an adjacent carbon. The stereochemistry of the product is most consistent with trans acetoxypalladation and cis Pd(II)-H(D) eliminations and additions (J27, 295) ... 

The oxidation of hex-l-ene, hex-m-2-ene, and 3,3-dimethylbut-l-ene catalytically under Oj proved to be complicated. Hex-l-ene gave mainly hex-l-en-2-yl acetate, the product expected by analogy with the acetoxypalladation Pd(II)-hydride mechanism. 3,3-Dimethylbut-l-ene also gave the expected product (23). Hex-cw-2-ene gave oxidation via a free-radical mechanism. Hex-l-ene also undergoes isomerization to hex-2-ene. 

Furthermore, a study of vinyl ester exchange, which proceeds by a mechanism analogous to the acetoxypalladation mechanism for olefin oxidation [see Section III, B, 1, Eqs. (174) and (175)], indicates that the dimer is the most catalytically active species, with the trimer next, and the monomer, (NaaPd(OAc)4), unreactive. In the study of Moiseev et ah, a maximum rate is attained at the point at which the concentration of Na2Pd2(OAc)g reaches a maximum. Thus the dimer is the reactive species rather than Na2Pd(OAc)4. However, the decrease in rate with increasing [NaOAc] is greater than can be explained on the basis of conversion of dimer to unreactive monomer [Eq. (5), Section II, A, 2]. 

It is interesting to compare this tentative rate expression with that found for vinyl ester exchange [Section III, B, 1, Eq. (173)] which does not contain the [NaOAc] inhibition term because of a cancellation of the inhibition term with a catalytic term in [NaOAc], The rate-determining step for the vinyl ester exchange is the acetoxypalladation step. The added term in the oxidation rate expression suggests that acetoxypalladation is not the slow step but rather the decomposition of the acetoxypalladation adduct. Furthermore, the decomposition must be inhibited by acetate. The following scheme is consistent with other Pd(II) as well as Pt(II) chemistry ... 

In the low [NaOAc] range, decomposition of the acetoxypalladation adduct would be fast. The proportion of compounds (XIII) and (XV) would depend on the relative rates of formation of compounds (XII) and (XIV), and the product distribution would be kinetically controlled. At high [NaOAc], the rate of decomposition of compounds (XII) and (XIV) would be inhibited, and they would have the opportunity to come to an equilibrium distribution. In this case the product distribution would be equilibrium controlled. 

The most reasonable mechanism appears to be the interception of the acetoxypalladation adduct by oxidant ... 

The mode of interaction of the oxidant with the acetoxypalladation adduct is not certain. The oxidant could be removing electrons from Pd as the Pd(II)—C bond is broken and Pd(0) is never formed, or the Pd(II) could be oxidized to Pd(IV) which would leave much more easily than Pd(II). Another possibility is that the organic radical is transferred to the oxidant followed by decomposition. It would be difficult to distinguish between the various possibilities. Related reactions are the cleavage of a-bonded palladium complexes with Collins reagent (280), decomposition of rr-allyls with oxidants (164), and the decomposition of oxypalladation adducts of diolefins with oxidants (Section IV, B). 

A recent study of the product distribution from cyclohexene in the presence of CuCl2 sheds some light of the stereochemical aspects of the reaction (114, 127). The products consisted of 1,2,- 1,3,- and 1,4-chloro- and diacetates plus the allylic and homoallylic acetates found in the absence of CuCl2. No enol acetate was detected. Only certain isomers were found. The diacetates were always the cis isomer, whereas the 1,3- and 1,4-chloroacetates were almost exclusively trans. The 1,2-chloroacetates were about in equal mixtures of cis and trans isomers. Also, deuterium-labeling studies indicated that acetoxypalladation was a trans process. Thus, the chloroacetates must be formed mainly by cis displacement of Pd(II) and diacetates by trans attack on the Pd(II)— carbon bond. For example, the scheme for formation of 1,2 and 1,3 products is shown in Eq. (99). 

Section III, B, 1). Thus, in chloride-containing acetic acid, acetate is not complexed to Pd(II) and acetoxypalladation is trans displacement of Pd(II) occurs in an Sj,2 fashion. Chloride is in the coordination sphere as well as in solution and can thus replace Pd(II) with either retention or inversion of configuration at carbon. 

The author also suggested an acetoxypalladation-dechloropalladation mechanism (19). Since these reactions do not result in the reduction of Pd(II) and give readily stereochemical information, they are well suited for mechanistic studies. A series of studies on various exchanges has recently been carried out to determine the factors involved in Pd(II)-catalyzed additions and eliminations (104). 

The second result confirms that acetoxypalladation is very stereospecific since only very pure, trans acetoxypalladation-deacetoxypallada-tion would prevent exchange in this system ... 

Stereochemical studies indicate that in this system acetoxypalladation is not stereospecific, as contrasted with the chloride-containing system. However, in this system acetate is a ligand and is, thus, available in the coordination sphere. The lack of an [NaOAc] term in the rate expression is believed to result in a cancellation in the two equilibria given by Eqs. (175) and (176) ... 

The acetoxypalladation adduct of norbornene has also been reported to rearrange to the nortricyclic system in the presence of triphenyl-phosphine (15). 

In an analogous reaction the acetoxypalladation adduct of 1,5-cyclo-octadiene reacted in acetic acid, containing traces of chloride in the presence of Pb(OAc)4, to give 2,6-cwinsertion into the second double bond, and trans elimination of Pd(II) with OAc ... 

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