Cascade carbopalladation alkene termination

Cascade carbopalladation sequences after attack on an alkene are most commonly terminated by dehydropallada-tion, if a / -hydride is available in a yy//-orientation. The intramolecular carbopalladation starting from the monocyclic diene 122 with a geminally disubstituted alkene terminator leads to a neopentylpalladium intermediate 123, which cannot undergo /J-dehydropalladation, but continue the cascade by a carbopalladation to eventually form the... 

Brase S, de Meijere A (2002) Palladium-Catalyzed Cascade Carbopalladation Termination with Alkenes, Arenes, and Related jr-Bond Systems. In Negishi E, de Meijere A (eds) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley, New York, p 1369... 

IV.3.1 Palladium-Catalyzed Cascade Carbopalladation Termination with Alkenes, Arenes, and Related ir-Bond Systems... 

B. INTER-INTRAMOLECULAR CASCADE CARBOPALLADATIONS B.i. Termination by Alkenes... 

Cascade carbopalladation sequences after attack on an alkene are most commonly terminated by dehydropalladation, if a /S-hydride is present in a yn-orientation (see above). 

D.i.a. Formation of Cyclopropane Derivatives by Two Successive Intramolecular Carbopalladations. Intramolecular carbopalladation starting from 1,( —l)-dienes with a suitable leaving group at the 2-position and a substituent at the (n-l)-position of the alkene terminator leads to a neopentylpalladium intermediate, which can only continue the cascade by a 3-eJto-tng-carbopalladation to eventually form bicyclo[(n—2). 1.0]alkenes. This sequence works equally well for ring sizes five, six, and seven in the first formed ring (Scheme 22) and even heterocyclic systems can be constructed by this mode (Scheme 22). 

D.i.b. Insertion of Another Alkenyl Unit In certain cases, however, the 3-exo-trig process may be retarded and an additional alkene moiety participates in the cascade carbopalladation. A pioneering example of this kind has been demonstrated by Overman and co-workers in their total synthesis of scopadulcic acid A, starting from an iodoaUcenyl-substituted methylenecycloheptene derivative (Scheme 24). The first intramolecular carbopalladation occurs across the disubstituted double bond of the exomethylene group, and the trisubstituted endocyclic double bond acts as the terminator to give a tricyclic system, which was further elaborated to the natural product (Scheme 24). It is remarkable that all three quaternary carbon centers can be created by intramolecular Heck reactions. 

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. 

IV.3.3 Palladium-Catalyzed Tandem and Cascade Carbopalladation of Alkynes and 1,1-Disubstituted Alkenes Terminated by Carbonylative Reactions... 

In principle, carbonylative cyclization, that is, acylpalladation or Ac—Pd process, or noncarbonylative cyclization, that is, sample carbopalladation or C—Pd process, in the presence of CO and a Pd catalyst. Various possibilities with halo alkenes as representative substrates are shown in Scheme 2P Those processes that incorporate CO in the cyclization processes are discussed in Part VI including Sects. VI.4-VI.6. hi this section, those cases that do not incorporate CO during the cychzation processes but do so only after cyclization will be discussed. Such cychc carbopalladation-carbonylative termination tandem and cascade processes are represented by the Type II C—Pd process in Scheme 2, which may take place in competition with the other processes shown in Scheme 2, especially the cyclic Heck reaction (Type 1 C—Pd process) and cyclic carbopalladation involving cyclopropa-nation (Type 111 C— Pd process). 

C. Pd-CATALYZED TANDEM AND CASCADE CARBOPALLADATION OF ALKENES TERMINATED BY CARBONYLATION... 

Erase, S. and de Meijere, A. (2002) Palladium-catalyzed tandem and cascade carbopalladation -termination with alkenes, arenes and related jr-compounds, mHandbook of Organo-Palladium Chemistry (ed. E.-i. Negishi), John WUey Sons Inc., New York, pp. 1369 05. 

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