Cyclopalladation-carbonylation

An improved procedure for cyclopalladation-carbonylation (of e.g. 320) relies on the addition of CuCl and LiCl to the standard PdCl2-CuCl2 mixture. This indicates that both the Cu2+ and Cu+ are required in sufficient concentrations to keep up the cascade of the catalytic cycle. This method is superior to the Hg(II)-mediated cyclization followed by transmetallation with Pd in CO/MeOH197. For application in the synthesis of polyether antibiotics, see elsewhere435. 

Vinyl substitutions with N,N-dialkylbenzylamine-cyclopalladated complexes have been studied most thoroughly. In the presence of triethylamine the substitution occurs quite selectively with styrene derivatives19 and a,p-unsaturated carbonyl compounds.20 For example, chloride-bridged cyclopalladated NJ4-dimethylbenzylamine dimer and methyl vinyl ketone give 92% of o-dimethylaminomethylbenzalacetone in 1 h at 110 C (equation 6). 

By palladium (O)-catalyzed carbonylation of l,2-diaza-l,3-buta-dienes. Boeckman et al. (01OL3651) (Scheme 42) reported that stable l-(l,2-diphenylethenyl)-2-phenyldiazene 180 when treated with 10 or 1 mol% of Pd(Ph3P)4 or Pd(dppe)2 catalysts, respectively, in toluene under 1 or 2 atm of carbon monoxide, at room temperature or 100 °C for 0.25-30 h, afforded pyrazol-3-one 184 in excellent yields. Although no intermediates were detected, by analogy to the previously studied cyclopalladation of azobenzene, the mechanism shown in Scheme 42 was proposed. The mechanism involves formation of a cr-complex 181 between 180 and Pd(0)-catalyst, cycloaddition by n—>-n isomerization to... 

A chloro-bridged cyclopalladated pyridine compound is also carbonylated by the reaction of carbon monoxide with bubbling through a reaction mixture at room temperature in the presence of NEts as a proton scavenger. Metalhc palladium is separated out, while ethyl ester 7.62 is recovered in a 73 % yield, as shown in Eq. (7.41) [94]. 

D.xi.a. Hydrolysis and Hydration. The electrophilicity of cationic palladium(II) complexes has been taken advantage of in an interesting biomimetic method of selective cleavage of peptide bonds at histidine, methionine, or tryptophane residues. Further discrimination is possible as peptides with two former amino acids are cleaved in aqueous solution but not cleaved in acetone, while those with tryptophane are cleaved only in acetone in the presence of water. The mechanism of cleavage at tryptophane is particularly interesting as it involves the electrophilic ip o-paUadation of indole ring, while the remaining coordination site of Pd in the ip/ro-cyclopalladated complex is used for the electrophilic activation of carbonyl (Scheme 91). 

The cyclopalladated complex (69), formed in 60% yield from the appropriate acetanilide and Pd(OAc)2, reacts with various a,/3-unsaturated carbonyl compounds to give the intermediate (70) which can then undergo acid-catalysed cyclization to compound (71). The last two steps each proceed in yields of 40—80%. 

The insertion of metallacarbynes of molybdenum into the palladium-methyl bond (non-cyclopalladated) has also been carried out, similarly giving /x-alkylidene, p-carbonyl dimers. The resultant complexes seem to display similar bonding characteristics to the cyclopalladated complexes, although are less stable in solution. 

The ortfro-acylation of IV-benzyltriflamides with benzylic and aliphatic alcohols has been reported using palladiiun catalysis with t-butyl hydroperoxide (TBHP) as an oxidant. The reaction is likely to involve formation of acyl radicals from the alcohols and their reaction with a cyclopalladated intermediate to produce (149). Reductive elimination yields the acylated product. A similar pathway is probable in the palladium-catalysed ortfro-acylation of 2-arylbenzothiazoles to give derivatives (150). There has been an investigation involving both kinetic and DFT studies of the factors affecting the reactivity of aminoesters in cyclopalladation reactions carbonylation may yield products such as (151). 

A further experiment was especially significant (Scheme 15.6). Treatment of the substrate with the standard conditions only gave the six-membered ring lactam. In contrast, the first cyclometalation of substrate gave the favored five-membered palladacycle which was applied to the carbonylation with CO in the absence of BQ, affording the five-membered lactam in 86% yield as well as a minor amount (6%) of the isomer. The steric hindrance around the amino group is pivotal for the success of this transformation because the full substitution of the carbon in a-position of the amino esters plays an important role in their cyclopalladation step. 

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