Cyclopalladation reactions

An unactivated methyl group can be functionalized by the cyclopalladation of oximes. The equatorial methyl of geminal methyls in steroids or hexapyr-anosides is selectively aceto.xylated by the reaction of the palladation complex 523 of the 3-oxime with lead tetraacetate[467,468]. 

TL2403). Thus, or /io-cyclopalladation of acetanilide 138 gave organo-palladium reagent 139. The or /io-vinylation of 139 afforded enone 140, which was then cyclized to quinoline 141 under acidic conditions. Notice this reaction requires stoichiometric amounts of Pd(OAc)2. 

Methylphenyl)benzothiazole (80IC762) and 2-benzylbenzothiazole (95ICA(239)125) can be cyclopalladated. In the latter case, cylopalladation occurs upon reaction with palladium(II) acetate and gives the product 80. With lithium chloride, sodium bromide, or sodium iodide, a series of three products of substitution of the acetate group 81 (X = C1, Br, I) results. Pyridine, 2- and 3-methylpyridine, 2,6- and 3,5-dimethylpyridine cause the transformation of the chelate complexes 81 (X = C1, Br, I) and formation of the mononuclear products 82 (R = z= R" = = R = H, X = Cl, Br, I ... 

Kostic el al. discovered that Pd11 complexes, when attached to tryptophan residues, can rapidly cleave peptides in acetone solutions to which a stoichiometric amount of water is added, for hydrolysis.436 The indole tautomer in which a hydrogen has moved from the nitrogen to C(3) is named indolenine. Its palladium(II) complexes that are coordinated via the nitrogen atom have been characterized by X-ray crystallography and spectroscopic methods.451 Binuclear dimeric complexes between palladium(II) and indole-3-acetate involve cyclopalladation.452 Bidentate coordination to palladium(II) through the N(l) and the C(2) atoms occurs in binuclear complexes.453 Reactions of palladium(II) complexes with indole-3-acetamide and its derivatives produced new complexes of unusual structure. Various NMR, UV, IR, and mass spectral analyses have revealed bidentate coordination via the indole carbon C(3) and the amide oxygen.437... 

Diastereomerically pure (2W,5.V)-l,3-diaza-2-(2-methylphenyl)-3-phenyl-2-phosphabicyclo[3.3.0]octane (.S )-202] was formed in the thermal reaction of (S)-2-(anilinomethyl)pyrrolidines (197a) with o-TolP(NMe2)2 and isolated in 27% yield after recrystallization (Scheme 56) [87], Its cyclopalladation with palladium diacetate followed by anion metathesis gave dimer (5,5)-203 (Scheme 56) [87],... 

The insertion of allenes in the Pd-C bond of cyclopalladated 3-arylisoquinoline derivatives 327 afforded compounds 328, derived from the berberinium cation (Scheme 71). This reaction takes place via the formation of an intermediate (r/ -allyOpalladium complex <2003JOM313>. This chemistry has been extended to the preparation of other cationic N-heterocycles, including naphtho[r+/ ]( uinolizinium derivatives <2004EJ01724>. 

Cyclopalladated complexes provide a potential use for regiospecifically controlled organic syntheses.1 Various substituents can be introduced onto the palladated carbon position by reactions of cyclopalladated complexes with various reagents.2-4 Cyclopalladation of aryl-substituted nitrogen or phosphorus bases has been performed mainly by use of [PdCl4]2- or PdCl2(NCPh)2 in the presence or absence of an acetate salt, but this method appears to have limit in applicability.5,6 Here, we describe a preparation of a rare six-membered cyclopalladated complex of 2-benzylpyridine by use of palladium(II) acetate,7 which seems to be a better starting material for syntheses of cyclopalladated species.6,7 Only five reports of six-membered cyclopalladated complexes have appeared.7,8... 

To a suspension of the cyclopalladated compound (12.95 g, 47 mmol) in acetone (300 mL) is added an excess of LiCl (6.77 g, 150 mmol). This mixture is heated with vigorous stirring until the precipitate has dissolved. It is likely that with an excess of LiCl the salt Li[PdC6H4CH2N(CH3)2Cl2] is formed, which is stable only in acetone in the absence of water. Addition of water to this solution affords immediately the chloro-bridged dimer. The yellow solution is then quickly filtered over a short column of Celite (3 cm) to retain the finely divided metallic palladium and the column washed with 50 mL of acetone. The solution thus obtained is poured into a beaker containing 400 mL of water affording a yellow precipitate. The more quickly this operation is done the better the yield of the reaction the overall time of this purification should not... 

The moderate yield of cyclopalladated products could be increased using ligand exchange reactions starting from another cyclopalladated complex.131 Other thioketones such as thioxanthone, dithioxanthone, and thio-chromone derivatives react in a similar way, affording cyclopalladated compounds.132... 

An intermediate in the reaction of bis(hexafluoroacetylacetonato)-palladium with S = C(C6HdOMe-p)2 to give the cyclopalladated complex 12 could be observed at low temperatures. In the intermediate the thioben-zophenone is 771 coordinated to the metal and one acetylacetonato ligand via the central carbon atom. Subsequent loss of the cr-coordinated acetyl-acetonate afforded 12 (Scheme 4).133... 

Stable, cyclopalladated complexes sometimes may be used in vinyl substitution but these reactions cannot be carried out catalytically. A major limitation is that few cyclopalladated structures are available and only a few types of vinyl substitution products can be made by this procedure. 

Scheme8.22. Cyclopalladation during Pd-mediated homocoupling of aryl iodides [156] and Heck reaction with norbornene [157]. Ar = 2-(tBu)C6H4.

Other intermediates which can undergo similar cyclometalations include (2-methoxyphenyl)palladium [158, 159] and (l-naphthylmethyl)palladium complexes (Scheme 8.23) [160], Cyclometalation is usually promoted by high temperatures, and if these are necessary the yield of cross-coupling reactions with substrates prone to undergo cyclopalladation (for example 2-bromoanisole) can drop dramatically [43]. 

The cyclopalladation reactions of cobalt tetraphenylcyclobutadienepentadienyl-oxazoline are described in Ref. 498. 

Although introduced separately, transmetalation (catalytic Cycle 2) and cyclopal-ladation (catalytic Cycle 1) were found to be competitive processes under given arylation reaction conditions. Because 6 is ineffective in catalyzing the desired transformation, any condition that favors its formation (fast C-H bond activation before transmetalation) would inhibit the arylation process. Thus, substrates that form stable five membered cyclopalladated complexes will fail to undergo the arylation reaction (see Section 1.4.3). 

Apart from these successful transformations, the method has its limitations. As already mentioned, the success of this arylation and alkenylation reaction depends on a delicate balance of rates of transmetalation and C-H bond activation. For substrate 19, rapid benzylic C-H bond activation is favored over formation of the six-membered cyclopalladated intermediate, which in turn gives rise to complex 20 instead of the arylation reaction (Scheme 6). Furthermore, substrate 21, does not undergo the arylation reaction but follows the competitive pathway to form five membered cyclopalladated complex 22. 

Most recently, Monteiro et al. have reported that cyclopalladated compounds derived from the ortho-metalation of benzylic tert-butyl thioethers are excellent catalyst precursors for the Suzuki cross-coupling reaction of aryl bromides and chlorides with phenylboronic acid under mild reaction conditions. A broad range of substrates and functional groups are tolerated in this protocol, and high catalytic activity is attained (Eq. (58)) [93]. 

This reaction seems to involve coordination of the phenolate oxygen to aryl-palladium intermediate and the successive cyclopalladation as the key steps. This is similar to the arylation of biphenyl-2-ols in Eqs. (56) and (57). A similar intramolecular reaction of haloaryl-linked aldehydes to give cyclic ketones is found in Eq. (20). This occurs along with a-arylation. 

The Shaw cyclopalladation reaction (equation 10), reported in 1978, has been developed sufficiently to conclude that it has considerable potenti for functionalization of unactivated methyl groups in die vicinity of a ketone, via the oxime. This was demonstrated with lanost-8-en-3-one, which furnished a cy-clopalladated derivative (32), which allowed functionalization of the 4-Me gro i to CH2D (NaBD4) and CH2I (Ij/CHCls). Attempted oxidation of the cyclohexanone derivative (33) with MCPBA unexpectedly provided the chloromethyl compound (Scheme 29). 

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