Cascade reactions carbon-palladium bonds

A series of optically active hydroxylactones 109 with various substituents could be constructed efficiently using this cascade reaction. The insertion of ketones into carbon-palladium bonds is uncommon, which is quite different from the insertion of alkenes into C—Pd bonds. Unfortunately, the authors did not confirm the absolute configuration of the products. 

It is worth mentioning that some precursors easily catalyze the reductive carbonylation of alkynes from the C0/H20 couple. Here, the main role of water is to furnish hydrogen through the water-gas-shift reaction, as evidenced by the co-production of CO2. In the presence of Pd /KI terminal alkynes have been selectively converted into furan-2-(5H)-ones or anhydrides when a high concentration in CO2 is maintained. Two CO building blocks are incorporated and the cascade reactions that occur on palladium result in a cyclization together with the formation of an oxygen-carbon bond [37,38]. Two examples are shown in Scheme 4. 

In more complex reaction cascades an additional alkyne-insertion step can occur. Thus starting with intramolecular carbopalladation of a vinyl iodide to a carbon-carbon triple bond, followed by two intramolecular alkene-insertion steps and termination with dehydropalladation, a palladium-catalyzed synthesis of l-(5 -methylbicyclo[3.1.0]hex-T-yl)-5,5-bis(carboethoxy)cyclo-hexadiene (52) starting from l-iodo-4,4-bis(carboethoxy)-ll-methyldodeca-l,ll-dien-6-yne (51) is achieved. ... 

Cascade reactions arising from sequential carbopalladations are especially valuable for the construction of various carbo- and heterooligocyclic systans with three, four, or even more annelated rings. The Heck reaction has successfully been employed in various inter-inter-, intra-inter-, as well as all-intramolecular reaction cascades (Sect. IV.3). In the carbopalladation step of the Heck reaction (Scheme 6) a new metal-carbon bond is formed, which, in principle, can undergo any of the typical reactions of a hydride elimination is not too fast. When the /S-hydride elimination is totally suppressed, the palladium species can undergo a number of reactions with the formation... 

Abstract Palladium-catalyzed multicomponent coupling and annulation reactions have become important tools in organic synthesis. Recently, palladium(IV) complexes have been proposed as intermediates in catalytic cycles of these transformations, although experimental evidence for their involvement is frequently lacking. Examples of such catalytic annulation reactions are discussed, followed by a review of studies performed with stoichiometric isolable or semistable palladium(IV) complexes seeking experimental evidence for feasibility of the participation of palladium(IV) intermediates in cascade carbon-carbon and carbon-heteroatom bond-forming sequences. 

The carbonylative palladium-catalyzed reactions discussed in this section proceed by oxidative addition of palladium (0) to the carbon-X bond of aryl/vinyl/acyl halides and pseudohalides followed by carbon monoxide insertion, giving rise to an acylpalla-dium intermediate. The acylpalladium intermediate can in turn react with various tethered nucleophiles (a), be involved in activation/hetero or carbopalladation steps with unsaturated carbon-carbon bonds (b), or participate in cascade reactions (c) (Scheme 13.1). 

In 2003, Zhu and Zhang reported a palladium-catalyzed cyclization/arylation cascade reactions of enynes with arylboronic acids leading to cyclic products with a stereodefined exocyclic double bond [44] (Scheme 6.26). Several types of enynes can be anployed carbon, oxygen, and nitrogen tethers [Y=C(COjMe)j, O, Ts], and alkyl- and arylalkynes are well tolerated. The author proposed a plausible mechanism, probably involving a Jt-allylpalladium complex which is formed from the aUyUc halide, followed by insertion of the alkynes and Suzuki coupling reactions. 

In a formally similar reaction an alkene and an alkyne moiety were coupled in the presence of a palladium catalyst in formic acid. The reaction cascade in this case starts by the hydropalladation of the triple bond, which is followed by a Heck-type carbon-carbon bond formation. Running the... 

A cascade Heck reaction with termination by nucleophiles is considered to start with an oxidative addition of a heteroatom-carbon bond (starter) onto a palladium(O) species (startup reaction), followed by carbopalladation of a nonaromatic carbon-carbon double or triple bond without subsequent dehydropalladation (relay), a second and possibly further carbopalladation of a carbon-carbon double or triple bond (second etc. relay). The terminating step is a displacement of the palladium residue by an appropriate nucleophile. It is crucial for a successful cascade carbopalladation that no premature dehydropalladation takes place, and that can be prevented by using alkynes and 1,1-disubstituted alkenes (or certain cycloalkenes) as relay stations since they give kinetically stable alkenyl- or neopentylpalladium intermediates, respectively. In addition, reaction of haloalkenes with alkenes in certain cases may form rr-allyl complexes, which are then trapped by various nucleophiles. 

This Pd-catalyzed cascade bis-cyclization reaction can also be applied to trans linear substrates 40 and 41. It was possible to effect either 5-exo or 6-endo cyclizalion selectively by an appropriate choice of the electron-withdrawing substituents of the nucleophile, as illustrated in Scheme 20. Ero-cyclizations were observed when sterically encumbered nucleophiles were employed. Cyclopentanes were obtained as a result of steric interactions between the nucleophile and one of the allylic hydrogens of the linear substrate. Endo-cyclizations leading to trani-octahydrophenanthrene were the only reactions observed when less sterically demanding nucleophiles were employed. Notably, these cyclizations proceed in a completely stereoselective trans manner. Attack of the carbon nucleophile onto a double bond electrophilicaUy activated by the palladium species results in a trans configuration of the fused ring junction. This stereochemistry is defined by that of the double bond in the initial substrate the relative configuration of compound 42 or 43 is hereby controlled. 

Palladium-catalyzed hydroboration, haloboration, and similar reactions involving addition of organoboron compounds to alkynes have been reviewed.Alkylborane addition to alkynes followed by intra- or intermolecular cross-coupling with a vinyl halide or triflates according to the Suzuki-Miyaura protocol constitutes a very powerful synthetic route for the generation of two carbon-carbon bonds in cascade. This subject and its applications in synthesis have been reviewed. ... 

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