Organopalladium functionalization

Termination of cascade carbopalladation sequences by arylation can play a major role in systems that form a reasonably long-lived palladium intermediate and contain a suitably functionalized arene moiety in the vicinity of the organopalladium function. In particular, neopentylpalladium intermediates have been found to intramolecularly attack an adjacent arene moiety. For example, iodoarenes 149 with electron-withdrawing substituents in the... 

Attachment of pyridine- and phosphine-functionalities to oxalamidine ligands has also been achieved. Scheme 199 exemplifies the use of such ligands in the synthesis of novel organopalladium oxalamidinate com-... 

Palladium-catalyzed coupling reactions of the Heck type have in many instances involved indole and pyrrole derivatives. Although the mechanisms are complex, organopalladium species are implicated (84H(22)1493). Vinylation of A-substituted-3 -iodoindoles with amidoacrylate groups provides a useful functionalization of indoles (Scheme 81) (90JOM(39l)C23). Yields are improved in intramolecular reactions, e.g. (406 — 407) and (408 — 409) <92H(34)219,91CPB2830). 

An interesting series of transformations have been reported which demonstrate a variety of selecti-vities of organopalladium chemistry. 1,3-Dienes can be regioselectively functionalized in a 1,4-fashion... 

The insertion reaction is stereospecific and syn. Moreover the /S-hydride elimination is also syn. For acyclic alkenes there is free rotation in the organopalladium intermediate so that the more stable /ra .v-alkene is formed. Electron-withdrawing groups in the alkene also increase the rate of the insertion reaction and give higher yields generally, but the reaction is limited to relatively sterically unhindered alkenes. In general, polar solvents such as DMF or acetonitrile are most commonly used. There are several common additives which aid in the reaction. These include lithium or tetraalkylammonium chlorides and bromide, silver salts, or cuprous iodide, but exactly how they function is unknown at present. 

The organopalladium addition reactions to produce substituted olefinic compounds are very useful laboratory syntheses since a wide variety of substituents and functional groups can be present in both the organopalladium species and the olefin. The only groups which may inhibit the reaction to some extent are ones which form stable complexes with the palladium salt, such as unhindered amines. Lower yields are generally... 

Much work has gone into the optimization of results with functionalized alkenes. In the reaction of cyclic alkenes, ds-decomposition of organopalladium halide-alkene complex gives -palladium complex 41. This subsequently undergoes syn-p-hydride elimination since only one such hydrogen is available, deconjugation to 3-substituted alkenes should... 

Over the past 30 0 years, organopalladium chemistry has found widespread use in organic synthesis, and has been described in detail in a number of useful and informative books [1]. Palladium catalysts facilitate unique transformations that carmot be readily achieved using classical techniques, and in many cases palladium-catalyzed reactions proceed under mild reaction conditions and tolerate a broad array of functional groups. As such, the use of palladium catalysts for the synthesis of important, biologically active heterocyclic compounds has been the focus of a considerable amount of research [2],... 

Functionalization at sp-carbons. Several different oxidants have been employed in oxidative functionalization. For o-acetoxylation of acylaminoarenes K2S2O8 is the oxidant, and oxone is present to facilitate the transfer of an ethoxycarhonyl group from DEAD to organopalladium intermediates. ... 

The Heck reaction, a palladium-catalyzed vinylic substitution, is conducted with olefins organohalides or pseudohalides are frequently used as organopalladium precursors [143]. One of the strengths of the method is that it enables direct mono-functionalization of a vinylic carbon, which is difficult to achieve by other means. The Heck arylation in Scheme 15.74, reported in 1996, was the first example of a microwave-promoted, palladium-catalyzed C-C bond formation [18]. The power... 

This review will not attempt to cover the many important reactions of functionally substituted alkynes where Pd(II) salts or organopalladium compounds (RPdX) react with the alkyne to promote cyclization onto the functionality already residing in the alkyne unit. That work has recently been reviewed by the present author in a separate book chapter, along with a large number of other... 

Internal alkynes will also readily undergo palladium-catalyzed annulation by functionally substituted aromatic or vinylic halides to afford a wide range of heterocycles and carbocycles. However, the mechanism here appears to be quite different from the mechanism for the annulation of terminal alkynes. In this case, it appears that the reaction usually involves (1) oxidative addition of the organic halide to Pd(0) to produce an organopalladium(II) intermediate, (2) subsequent insertion of the alkyne to produce a vinylic palladium intermediate, (3) cyclization to afford a palladacycle, and (4) reductive elimination to produce the cyclic product and regenerate the Pd(0) catalyst (Eq. 28). 

I have selected a number of important topics in newly developed organopalladium chemistry, and have asked researchers who have made important contributions to these fields to review them. I am pleased that most of them have kindly accepted my request. For this book I have selected recent advances (covering mainly the last five years), most of which have not previously been the object of reviews. The book I am editing will cover Pd-catalyzed reactions that are novel, and entirely different from the more standard ones. Considerable patience will be required by readers when they face and try to understand topics such as (3-carbon elimination, palladacycles, Pd/norbornene-catalyzed aromatic functionalizations, arylation of aromatics, three-component cycliza-tions of allenes, and cycloaddition of arynes, for example. I believe their efforts will be well rewarded. 

Of all the transition metals, palladium has found the most widespread use in organic synthesis. Organopalladium species tolerate many different functional groups and promote a variety of carbon-carbon (and other) bond-forming reactions with extremely high chemo- and regioselectivity. 

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