Neopentylpalladium intermediates

The benzene derivative 401 by the intermolecular insertion of acrylate[278], A formal [2 + 2+2] cycloaddition takes place by the reaction of 2-iodonitroben-zene with the 1,6-enyne 402. The neopentylpalladium intermediate 403 undergoes 6-endo-lrig cyclization on to the aromatic ring to give 404[279],... 

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... 

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... 

The 2-bromotetradeca-l,13-diene-7-yne 160 with its terminal phenyl group apparently also prefers to undergo a cascade cyclization via a neopentylpalladium intermediate with attack on the eventually proximal phenyl group to yield the pentacyclic system 161 (Scheme 39). ... 

Cascade reactions are often triggered when a 5 yn-j0-hydride elimination cannot take place, e.g., in a cycloalkyl- or neopentylpalladium intermediate. Such systems then seek an alternative reaction mode. 

When neopentylpalladium intermediates are generated under non-nucleophilic conditions C—H activation is the course they pursue." ... 

Some examples of termination by anion capture are as follows. Reactions are terminated by carbonylation. Domino carbopalladation and carbonylation of the iododiene 163 under 1 atm of CO via a neopentylpalladium intermediate gave the cyclized ester 164 with high yield and diastereoselectivity [82], The iodide 165 underwent 5-exo cyclization to generate the neopentylpalladium 166 and its carbonylation gave the acylpalladium 167. Intramolecular attack by malonate anion affords 168 [83]. 

Numerous carbo- and heterocyclic compounds of various sizes have been prepared by HR-type monocyclization. Cyclopropanes are formed only when neopentylpalladium intermediates are formed in the absence of anions. Intramolecular carbopalladation of the alkenyl triflate 201 generates the neopentylpalladium 202, and its 3-exo cyclization and jd-H elimination afford the cyclopropane 203 [95]. Intermolecular carbopalladation of the alkyne 204 generates 205. Its 5-exo cyclization provides the neopentylpalladium 206, which undergoes 3-exo cyclization to construct the three-membered ring 207. Finally y3-H elimination gives rise to the cyclopropane 208 [96]. 

Intramolecular carbopalladations usually are fast processes, which are terminated by de-hydropalladation unless the carbopalladation leads to an alkenyl- or neopentylpalladium intermediate, in which cases cascade carbopalladation sequences can be set off with other externally or internally available rr-systems. 

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). 

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. 

A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

The intermolecular carbopalladation of a triple bond can be faster than that of an intramolecular double bond as, for example, in the (9-iodo(l-methylallyl)benzene 152. The arylpalladium iodide initially formed from 152 and a palladium(O) species intermolecularly carbopalladates diphenylacetylene 71, and only the thus formed alkenylpalla-dium intermediate 153 undergoes insertion into the internal double bond to furnish the neopentylpalladium species 154 which, by <9r/ (9-attack on the adjacent phenyl group, finally forms the tetracyclic system 155. ... 

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