Cyclopalladated substrates

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]. 

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]. 

An interesting application of the chiral cyclopalladated complexes is palladium-promoted asymmetric Diels-Alder reactions of l-phenyl-3,4-dimethylphosphole (Scheme 4). In the original report on the Diels-Alder reaction of the phosphole reported by Nelson and co-workers, the dichloropalladium species was employed as a promoter.f In 1994, Leung showed that a chiral cyclopalladated complex was capable of promoting the Diels-Alder reaction. In this reaction, the chiral palladacycle worked as a chiral auxihary and showed almost perfect diastereoselectivity. It has been revealed that simultaneous precoordination of a diene and a dienophile to the palladium center is essential for the reaction. Thus, both dienes and dienophiles should possess Lewis basic functionahty. The diene l-phenyl-3,4-dimethylphosphole has been the only substrate examined so far, while a variety of dienophiles, such as vinylphosphine, vinyl-sulfoxide, vinylsulfide, acrylamide, vinylarsine, vinylpyridine, vinyl-pyrrole, or methylenequinuchdinone, have successfully been applied to this asymmetric Diels-Alder reaction. 

Numerous azobenzenes and imines have been used to prepare cyclopalladated ctmiplexes, and the liquid crystal properties of some of die products have been investigated. 1 Cyclometallated derivatives have also been prepared from 2-phenylpyiidines, > 2,6-diphenylpyridine, 6-phenyl bipy. O and 6-(2-thienyl) bipy.509 Other substrates subjected to cyclopalladation include amidines, thio- and selenoamides, ll> l N-phenylsulftmyl glycine, hydroxyquinoline derivatives, the drugs diazepam and prazepam, and PBu 3. Doubly cyclopalladated complexes have been prepared from 1,3-diacetylbenzene dioxime and also from N,N-dialkyl benzene-l,3-dicarbaldimines. The 2D NMR spectra of cyclopalladated 8-methylquinoline and benzo-(h)-quinoline show that a CH bond occupies a fifth coordination position above the square plane.520... 

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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