Palladium acylation

The insertion of unsaturated molecules into metal-carbon bonds is a critically important step in many transition-metal catalyzed organic transformations. The difference in insertion propensity of carbon-carbon and carbon-nitrogen multiple bonds can be attributed to the coordination characteristics of the respective molecules. The difficulty in achieving a to it isomerization may be the reason for the paucity of imine insertions. The synthesis of amides by the insertion of imines into palladium(II)-acyl bonds is the first direct observation of the insertion of imines into bonds between transition metals and carbon (see Scheme 7). The alternating copolymerization of imines with carbon monoxide (in which the insertion of the imine into palladium-acyl bonds would be the key step in the chain growth sequence), if successful, should constitute a new procedure for the synthesis of polypeptides (see Scheme 7).348... 

A similar involvement of palladium hydride, palladium alkyl, and palladium acyl complexes as intermediates in the catalytic cycle of the Pd-catalyzed hydroxycarbonylation of alkenes was reported for the aqueous-phase analogs. The cationic hydride PdH(TPPTS)3]+ was formed via the reduction of the Pd11 complex with CO and H20 to [Pd(TPPTS)3] and subsequent protonation in the acidic medium. The reaction of the hydride complex with ethene produced two new compounds, [Pd(Et)(TPPTS)3]+ and Pd(Et)(solvent)(TPPTS)2]+. The sample containing the mixture of palladium alkyl complexes reacted readily with CO to afford trans-[Pd(C(Q)Et)(TPPTS)2]+.665... 

Figure 15.8 a simple example is presented of a subsequent insertion of CO and methanolysis of the palladium acyl intermediate [14], This is not a very common reaction, because both the ligand requirements and the redox conditions for Wacker and carbonylation chemistry are not compatible. For insertion reactions one would use cis coordinating diphosphines or diimines, which makes the palladium centre more electron-rich and thus the nucleophilic attack in the Wacker part of the scheme will be slowed down. In addition, the oxidants present may lead to catalytic oxidation of carbon monoxide. 

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has contributed remarkably to unravelling the termination and initiation steps of the styrene/CO copolymerisation catalysed by the highly active bis-chelated complex [Pd(bipy)2](Pp5)2 in TFE [40]. Chain-end group analysis of the material produced in the absence of BQ showed that the termination by P-H elimination is accompanied by three different initiators two palladium alkyls from Pd-H formed by reaction of the precursor with CO and water (a and b) and a palladium carboalkoxy species formed by reaction of the precursor with the fluorinated alcohol and CO (c) (Chart 7.4). The suppression of the chain-transfer by alcoholysis was proposed to be responsible for the enhanced stability of the palladium acyl intermediates and hence for the high molecular weight of the copolymers produced. 

When a reaetion similar to that of Eq. 3 was performed with the palladium acyl precursor (-10 to 25 °C, 3 h), no pure complex could be isolated but the palladium analogue of 5a was observed spectroscopically and identified by comparison with an authentic sample prepared quantitatively according to Eq. 4. We felt that a reason for the formation of complexes 5 instead of 4 in reaction 3 could be the presence of PPh3. Indeed, the direct reaction of 4 with one equivalent of PR3 in CH2CI2 at ambient temperature also yielded 5 (Eq. 4). 

IR spectroscopy can aid in the identification of some Pd-C gronps. Palladium acyls generally have a strong absorption between 1630 and 1720 cm. a-bonded palladium alkynes have an absorption band of variable intensity between 1950 and 2125 cm, and a-alkenes have vc=c between 1535 and 1630 cm . ... 

Acylpalladium complexes are readily prepared through oxidative addition of Pd° complexes to acid chlorides. PdL4 compounds, where L is a tertiary phosphine, react with acid chlorides at room temperature to give trani-L2Pd(COR)Cl complexes. Since carbon monoxide does not insert into palladium acyl bonds, Pd(C0C02R) complexes are made from oxidative addition of oxalyl chloride monoesters. 

Aldehyde C-H bonds can also undergo cyclometalation with palladium salts. Reaction of 8-quinolinecarbaldehyde with PdCLt gives a chloride-bridged dimer with a palladium-acyl bond (equation 75). No intermediates could be isolated in case of the palladium reaction, but when [(PEt3)PtCl2]2 is reacted with 8-quinolinecarbaldehyde, a platinum complex is isolated with an intact aldehyde C-H bond. The nitrogen atom of the quinoline is coordinated to the platinum, and the aldehyde C-H bond occupies an axial site in the complex. Heating this material results in insertion into the aldehyde C-H bond and formation of a chelated platinmn acyl. 

Carbon monoxide insertion in a palladium-carbon bond is a fairly common reaction [21]. Under polymerization conditions, CO insertion is thought to be rapid and reversible. Olefin insertion in a palladium-carbon bond is a less common reaction, but recent studies involving cationic palladium-diphosphine and -bipyridyl complexes have shown that olefin insertion also, particularly in palladium-acyl bonds, appears to be a facile reaction [22], Nevertheless, it is likely that olefin insertion is the slowest (rate-determining) and irreversible step vide infra) in polyketone formation. 

A second mechanism, the alcoholysis of the palladium-acyl bond, gives an ester end-group and a palladium hydride species (eq. (7)), which is again an initiator for the next polymer chain. 

Stable species of this type have recently been observed by spectroscopic techniques in the studies of olefin insertion in palladium-acyls [21, 26]. The electrostatic interaction between the positive palladium center and the negative oxygen atom is probably the main driving force for chelate formation. This internal chelate coordination is expected to affect the chain propagation in a number of ways. 

Firstly, the stabilization by chelate formation should increase the exothermicity of olefin insertion. Since part of the stabilization will already be felt in the transition state, it will reduce the barrier for olefin insertion in a palladium-acyl bond. Secondly, chelate formation should oppose or slow down termination by ff-elimi-nation from palladium-alkyl. For -elimination to occur the P-R atom has to approach the palladium ion, but that is opposed by coordination of the carbonyl group (eq. (13)). Inhibition ofy9-H elimination in metallacycles is well known [27]. 

A somewhat more versatile synthesis of this type using stannanes and palladium acylations (Stille coupling) appeared subsequently (Fig. 1.16) (120). While precedent establishing, this was pharmacologically less... 

One reason for the perfect alternation is probably the stronger coordination of CO to palladium(II), compared with ethylene. Once a palladium-alfey/ is formed, the stronger CO coordination ensures that the next monomer to insert will usually be a CO molecule (assuming similar insertion barriers). Of course, CO also coordinates more strongly to a palladium-acyl but since the CO insertion is thermodynamically unfavorable, there the system will "wait " for an ethylene molecule to displace CO, to coordinate and insert (Scheme 5). 

Palladium acyl species can also undergo intramolecular acyl-palladation with alkenes to form five- and six-membered ring y-keto esters through exocyclic alkene insertion (eq 12). The carbonylative coupling of o-iodoaryl alkenyl ketones is also promoted by Pd(dba)2 to give bicyclic and polycyclic quinones through endocyclization followed by /3-H elimination. Sequential carbonylation and intramolecular insertion of propargylic and allylic alcohols provides a route to y-butyrolactones (eq 13). ... 

Palladium acyl complexes such as [Pd(COR)(MeCN)L2] BF4 or [Pd(COR)ClL2]/ AICI3 (L = PPh3) catalyze the isomerization of isobutyryl chloride to an equilibrium mixture with -butyryl chloride. The reaction probably proceeds via a palladium hydride intermediate which was not observed (Scheme 10). The turnover is slow up to 12.9 in 7 days. " Palladium cyclopropenylidene pyridine complexes (21) catalyze the isomerization of quadricyclane to norbomadiene at... 

Alkenes may also insert into the Pd-C bonds of some palladium acyl complexes, " " an important reaction that has been successfully applied to the synthesis of polyketones of general formula [-CH2CH2C(0)-] via the alternating co-polymerization of CO and ethylene (Scheme... 

Despite all the synthetic developments, relatively little detailed mechanistic work has been performed on Sonogashira carbonylations until the present. The generally accepted mechanism is shown in Scheme 5.25. The typical reaction begins with the oxidative addition of ArX to a palladium(0) complex to form an aryl palladium(II) intermediate. The subsequent insertion of CO leads to the respective palladium acyl complex. Transmetallation, and finally reductive elimination, releases the product and a new catalytic cycle can be started. Notably, all species passing through the cycle are believed to be in a reversible equilibrium. 

Vrieze and Elsevier and BrookharP - have studied insertions involved in the polymerization process. Brookhart and co-workers have quantified the origin of the nearly perfect alternation between the incorporation of carbon monoxide and ethyelene. The activation barriers for the various insertion steps involving palladium complexes of a bidentate phosphine are provided in Figure 17.10. - ° The activation energies for the insertion of carbon monoxide into the alkylpalladium complex to form an acylpalladium species and the insertion of ethylene into a cationic palladium acyl to form a y-keto alkylpalladium complex are both lower than that for insertion of ethylene into the palladium alkyl. These insertion reactions occur at -80 °C and -100 C with barriers of 13.4 and 12.3 kcal/mol, respectively. 

---