Carbopalladation nucleophilic substitution

The Pd—C cr-bond can be prepared from simple, unoxidized alkenes and aromatic compounds by the reaction of Pd(II) compounds. The following are typical examples. The first step of the reaction of a simple alkene with Pd(ll) and a nucleophile X or Y to form 19 is called palladation. Depending on the nucleophile, it is called oxypalladation, aminopalladation, carbopalladation, etc. The subsequent elimination of b-hydrogen produces the nucleophilic substitution product 20. The displacement of Pd with another nucleophile (X) affords the nucleophilic addition product 21 (see Chapter 3, Section 2). As an example, the oxypalladation of 4-pentenol with PdXi to afford furan 22 or 23 is shown. 

Oxidative carbonylation of alkenes is a unique reaction of Pd(II). Three types of oxidative carbonylation to give -substituted acid derivatives 130, a, -unsaturated esters 132 and succinate derivatives 134 are known, which can be understood by the following mechanism. Palladation of alkenes with PdX2, followed by CO insertion, generates the acylpalladium intermediate 129 whose reductive elimination affords -substituted carboxylic acid derivatives 130 (path a). Reaction in alcohol in the presence of a base starts by the formation of the alkoxycarbonylpalladium 128. Carbopalladation of alkene with 128 generates 131. Then y3-H elimination of the intermediate 131 yields the a-unsaturated ester 132 (path b). Further CO insertion to 131 gives the acylpalladium intermediate 133 and its alcoholysis yields the succinate derivative 134 (path c). Formation of the jS-alkoxy ester 130 (X-OR) is regarded as nucleophilic substitution of Pd-X in 131 with alcohols. 

While neopentyl-type and related cr-alkylpalladium complexes are stable toward dehy-dropalladation, all ordinary alkylpalladium complexes formed by carbopalladation of alkenes do undergo /S-hydride eUminalion more or less rapidly. However, under certain structural precondilions and also, to a certain extent, controlled by the external conditions, rearranganents, further carbopalladations (Sect. IV.3), transmetallations, car-bonylations, or nucleophilic substitutions (e.g., by hydride) can occur prior to /3-dehy-dropalladation. 

In Sect. B, the intermolecular carbopalladations of aUenes are followed by a /S-hydride elimination to afford a 1,3-diene. However, in the presence of a nucleophile, a Tsuji-Trost-type nucleophilic substitution of the intermediate Tr-allylpaUadium spedes has been fuUy established (Scheme 6). 

The Pd(OAc)2/dppb-catalyzed cascade reaction of o-iodophenol with 1,2-nonadiene and CO starts with a CO insertion which is followed by carbopalladation of the allene and subsequently terminated by an intramolecular nucleophilic substitution to afford O-con-taining six-membered a-methylenebenzo-y-dihydropyrones (Scheme 34). ... 

In 1995 Grigg and co-workers reported a similar cascade consisting of an intramolecular carbopalladation and intermolecular nucleophilic trapping (Scheme 44). The regioselectivity of the aUylic nucleophilic substitution can be controlled completely by using different bases. 

The intramolecular nucleophilic attack of a nitrogen atom on an allylpalladium complex was also used to construct a five and a six membered heterocycle in the same step. TV-substituted 2-iodobenzamides bearing an allene function in the appropriate distance from the iodine underwent cyclization through the carbopalladation of the allene moiety by the arylpalladium complex, formed in the first step of the catalytic cycle. The intermediate allylpalladium complex, part of a nine membered ring, cyclized readily to give the pyrroloisoquinolone derivative in excellent yield (4.23.). The nature of the added ligand and the solvent both had a marked influence on the efficiency of the transformation.26... 

Allenes undergo facile carbopalladation and are used extensively in organic synthesis. The general reaction patterns of allenes with aryl halides are as follows. In carbopalladation of allene, an Ar group attacks the central sp carbon of the allene system to generate 367 and then the 7r-allylpalladium 368 as an intermediate. Then the attack of a nucleophile mainly on a less substituted terminus yields the alkene 369. Thus 1,2-addition to one of the double bonds in the allene occurs. In the absence of nucleophiles, y3-H elimination gives 2-substituted 1,3-dienes... 

Oxygen nucleophiles have not frequently been used as terminators in cascade car-bometallation reactions. The intramolecular carbopalladation starting with an iodo- or trifluoromethylsulfonyloxyalkenyl-substituted derivative in the presence of tetrabutylam-monium acetate led to a suitable precursor of the sesquiterpene (-)-A (i )-capneUene. In this case, desymmetrization of the prochiral precursor was achieved using (5)-BINAP as the ligand on the palladium catalyst (Scheme 32). ... 

An analogous carbopalladation-cyclizaton process has been applied to the synthesis of various substituted tetrahydrofurans using three components. This one-pot procedure involves an intermolecnlar addition of allylic alkoxides to Michael acceptors. The resulting enolate nndergoes cyclization via nucleophilic attack on the alkene-Pd complex. So as to avoid nndesired side reactions snch as the premature trapping of the alkoxide by the organopalladinm species, the alkoxide shonld be added via a syringe pump. ... 

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