Cyclopalladated amines

For some time our laboratory has been actively involved in studying the reactivity of mainly cyclopalladated amines and thioethers with disubstituted alkynes. In many cases these reactions afford stable organometallic compounds in which the alkyne has inserted one to three times in the Pd-C bond (Scheme 3). Triple insertions are not discussed herein as they have already been covered in detail elsewhere. ... 

Hollis TK, Overman LE (1997) Cyclopalladated ferrocenyl amines as enantioselective catalysts for the rearrangement of allylic imidates to allylic amides. Tetrahedron Lett 38 8837-8840... 

Cohen F, Overman LE (1998) Planar-chiral cyclopalladated ferrocenyl amines and imines as enantioselective catalysts for allylic imidate rearrangements. Tetrahedron Asymmetry 9 3213-3222... 

The asymmetric aza-Claisen rearrangement of allyl imidates, (86) (87), has been shown to be catalysed by homochiral cationic palladium(II) complexes, and a series of enantiopure cyclopalladated ferrocenyl amines and imines have been... 

Miscellaneous Reactions of Phosphines. Procedures for the resolution of benzylcyclohexylphenylphosphine have been developed, involving adduct formation with cyclopalladated chiral amine complexes. A similar approach has also been used for the resolution of P-chiral secondary phosphines, e.g. (193). Treatment of t-butyl(di-o-tolyl)phosphine with potassium tetrachloro-palladate(ii) yields a cyclopalladated complex (194), involving chiral phos-... 

To obtain catalytically active compounds, a phosphine or a sulfide substituent has to be introduced in the position adjacent to the amine in the cyclopentadienyl ring. This is achieved by a metalation/substitution sequence. The metalation with alkyllithium reagents is a highly diastereoselective process which produces the diastereomers in a ratio of 96 421 22. Thus, from the (R)-amine, the (/ ,p/ )-lithioamine is obtained in high yield. As an alternative to the lithiation procedure, mercuration and cyclopalladation have been used for the preparation of phosphine derivatives32, however, this is a less convenient and less selective approach. 

The palladium-catalyzed annulation of alkynes by a couple of other halo-amine/amide systems has been reported to provide a useful route to nitrogen heterocycles. For example, 8-dimethylamino-l-iodonaphthalene reacts with internal alkynes in the presence of a cyclopalladation catalyst to afford N-methylbenzo[d,c]quinolines (Eq.48) [110]. 

Cyclopalladated complexes, which are most conunonly prepared from tetrachloropaUa-date(II) and appropriate amines or imines, have drawn the attention of inorganic, coordination, and organometallic chemists since the first report in 1965 (for imines) and in 1968 (for amines) by Cope and co-workers. ° These palladacycle species can easily be transformed into chiral form by employing corresponding chiral amines or imines. Two representative examples of the chiral cyclopalladated species are illustrated in Figure 1. This section will describe three examples that represent applications of these chiral orthometallated palladium complexes in organic synthesis. 

Cyclopalladation of the racemic secondary amine C6H4NHBu Me with Pd(OAc)2 in a mixture of benzene and glacial AcOH on heating gives a 3 1 mixture of regioisomeric complexes 50 and 51 (Scheme 13) Addition of excess acetic acid to this mixture led to the formation of a cyclopalladated imine complex. A related study with regard to the competition between sp and sp C-H bonds in cyclopalladation of A-G6H4NHBu Me was published in 2000. ... 

The complex [ PdCl(C6H4CH2NMe-o) 2] reacts with Ph3P=CHC(0)CH3PPh2 giving 62 (X = CP or BF4-). Primary amines such as 2-phenylaniline and (i )-o -methylbenzylamine were cyclopalladated with Pd(OAc)2 and LiBr to give the respective dimers/" Bridge-splitting reactions with pyridine and PPhs were carried out. 

The cyclopalladated complex (naphthyl)ethylamine-6, iV]-dipalladium has been used as a chiral template to promote the intramolecular [4 -h 2] Diels-Alder reaction between diphenyl-vinylphosphine and 1-phenyl-3,4-dimethylphosphole. Halide-bridged palladium(ii) dimers of orthopalladated (S)-(-h)-7V,7V-dimethyl-Q -methylbenzylamine and (naphthyl)ethyl]amine were reported by the same authors.Solution and solid-state structures were determined as well as reactions with 3,4-dimethyl-1-phenylphosphole and allyldiphenylphosphine carried out. 

The coupling of anilines with arylboronic acids has been described in a process catalysed by palladium acetate without the need for ligands, bases, or salts. The mechanism shown in Scheme 17, where S represents solvent, involves in situ formation of the dia-zonium salt from the aniline, and formation of an arylpalladium alkoxo complex which allows the transmetallation step with arylboronic acids. It has been shown that a free amine may be used as a DG in a palladium-catalysed reaction promoted by soluble silver salts. The latter aid the formation of intermediates, (136), which may undergo cyclopalladation followed by transmetallation with an arylboronic acid and reductive elimination. Related work has shown thatbiaryl-2-amines may react with aryl iodides in the presence of palladium acetate and silver acetate to give mono- or di-arylated species such as (137). 

The above three reactions employed ortAo-directing groups for assisted C—H activation in the presence of palladium(II) catalysts. The electrophilic fluorination reaction involved cyclopalladation and two electrophilic fluorination processes. Subtly, differential nitrogen atoms (pyridine, substituted amines, and amides) in the molecules were proposed to act as the electron donor, which is required for intramolecular Pd participation in the process. In this case, formation of a flve-membered palladium (II) complex (Schemes 9.12 and 9.13) has been proposed. ... 

The cyclopalladation of allylic or homoallylic amines and sulfides proceeds due to the chelating effect of N and S atoms, and has been used for functionalization of alkenes. For example, i-propyl 3-butenyl sulfide is carbopalladated with methyl cy-clopentanecarboxylate and Li2PdCl4. Reduction of the chelated complex with sodium cyanoborohydride affords the alkylated keto ester in 96% yield (eq 24). Functionalization of 3-N,N-dimethylaminocyclopentene for the synthesis of a prostaglandin skeleton has been carried out via a IV-chelated palladium complex as an intermediate. In the first step, malonate was introduced regio- and stereoselectively by carbopalladation (eq 25). Elimination of a /3-hydrogen generated a new cyclopentene, and its oxypalladation with 2-chloroethanol, followed by insertion of 1-octen-3-one and /3-elimination, afforded the final product. 

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