Carbopalladation Carbon-palladium bonds Heck reaction

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... 

Palladium-catalyzed vinylations of aryl halides are generally referred to as the Heck reaction (for reviews on the Heck reaction see [34-40]), a versatile process that can be performed inter- and intramolecularly [41]. In the Heck reaction the carbon-carbon single bond forming step is an insertion of an al-kene into the aryl-Pd bond, i.e., a carbopalladation, giving rise to an alkyl-Pd species. If this insertion is terminated by /1-hydride elimination the expected vinylation product is the outcome of the classical Heck reaction. Likewise, reversible insertion of a highly strained olefin where the /1-hydride elimination is suppressed leads to an entry to multiple Pd-catalyzed bond forming processes. 

C.i.a. Four-Centered Processes. The carbopalladation of a C,C multiple bond with a carbon-palladium single bonds is the key step in the catalytic cycle of the standard Heck reaction, the intermolecular version of which has been used extensively since its discovery for the functionalization and derivatization of aryl and alkenyl halides, as well as alkenyl triflates or the more reactive nonafiates, which are readily available from the corresponding ketones (Scheme 2) (Sect. IV.2.1.2). 

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. 

Carbopalladation has also been employed in the construction of six-membered rings. Most examples are 6-exo cyclizations as is the pyran ring synthesis (107—>108) used in the construction of ( )-6a-epipretazettine 109 and ( )-tazettine (Scheme 17). The Heck cyclization formed a quaternary center with a diastereoselectivity in excess of 20 1. The selectivity of the reaction is of particular interest in this case as it provides information about the orientation of the carbon-palladium a bond and the reacting aUcene in the carbopalladation transition state. Two limiting transition state geometries for the closure are intermediate 110, which leads to the observed product, and intermediate 111, which would lead to a diastereomer. In the preferred transition state 110, the carbon-palladium (7 bond and alkene are eclipsed, which is a lower energy state than the corresponding twisted orientation 111. 

Over 35 years ago, Richard F. Heck found that olefins can insert into the metal-carbon bond of arylpalladium species generated from organomercury compounds [1], The carbopalladation of olefins, stoichiometric at first, was made catalytic by Tsutomu Mizoroki, who coupled aryl iodides with ethylene under high pressure, in the presence of palladium chloride and sodium carbonate to neutralize the hydroiodic acid formed (Scheme 1) [2], Shortly thereafter, Heck disclosed a more general and practical procedure for this transformation, using palladium acetate as the catalyst and tri-w-butyl amine as the base [3], After investigations on stoichiometric reactions by Fitton et al. [4], it was also Heck who introduced palladium phosphine complexes as catalysts, enabling the decisive extension of the ole-fination reaction to inexpensive aryl bromides [5],... 

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