Carbopalladation allenes

The palladium(0)-catalyzed cyclization of amide-allenes via a carbopalladation has been developed by several groups. The reaction proceeds through the carbopalladation of the allene moiety with an organopalladium species (R-Pd-X), generated by oxidative addition of R-X to palladium(O), and subsequent reductive elimination of the resultant 7r-allylpalladium intermediate.47,47a 47f... 

An organic halide, RX (R = aryl or vinyl) adds oxidatively to Pd(0) species to form a RPdX species. An allene readily undergoes carbopalladation of the species to generate a jr-allylpalladium intermediate [3] in a highly regioselective manner. Finally, an allylic compound is produced by a nucleophile attack (Scheme 16.1). 

A one-pot synthesis of 3,3-disubstituted indolines was achieved by taking advantage of a sequential carbopalladation of allene, nucleophile attack, intramolecular insertion of an olefm and termination with NaBPh4 (Scheme 16.6) [10]. First, a Pd(0) species reacts with iodothiophene selectively to afford ArPdl, probably because the oxidative addition step is facilitated by coordination with the adjacent sulfur atom. Second, the ArPdl adds to allene, giving a Jt-allylpalladium complex, which is captured by a 2-iodoaniline derivative to afford an isolable allylic compound. Under more severe conditions, the oxidative addition of iodide to Pd(0) followed by the insertion of an internal olefm takes place to give an alkylpalladium complex, which is transmetallated with NaBPh4 to release the product. 

The possibility of Jt-allylpalladium complex formation through carbopalladation is excluded from the observation that no four- and/or six-membered rings are produced. The reaction apparently proceeds via an alternative pathway which involves a sequence of Jt-coordination of PhPdl to an allenic terminal double bond, oxypallada-tion and ensuing reductive elimination (Scheme 16.9). 

Homoallylic alcohols are provided by Pd-catalyzed reaction of iodobenzene, allene and aldehydes (Scheme 16.15) [19, 20]. A nucleophilic allylindium intermediate is generated through transmetallation of a Jt-allylpalladium species with indium. Such a Jt-allylpalladium complex can alternatively be provided through carbopalladation of ArPdl to a proximate acetylene followed by insertion of allene. 

Ma and Zhao reported a highly regio- and diastereoselective synthetic method for 2-amino-3-alken-l-ols and 4-amino-2-( )-alken-l-ols by the palladium-catalyzed reaction of 2,3-allenols, aryl iodides and amines (Scheme 16.24) [29]. Carbopalladation of PhPdl to the allene probably generates a thermodynamically more stable anti-Jt-allylpalladium species for steric reasons. Regioselectivity of the amine attack depends largely on the stereoelectronic effect on the a-substituents. 

Cyclizations Proceeding with Inter- and Intramolecular Carbopalladations of Allenes 327... 

Grigg and Xu have developed a variety of so-called queuing cascades involving allenes. The intra-intermolecular carbopalladation sequence of the <9-iodo-A-methyl-A -(methylallyl)aniline 142 and 1,1-dimethylallene 143 with subsequent / -dehydropalladation leads to the 1,3-dienyl-substituted indole derivative 144, which is immediately trapped by an added dienophile (e.g., A-methylmaleimide) in a Diels-Alder reaction to yield 145 (Scheme 37)7 ... 

Under palladium catalysis, the < -iodoallenylbenzene 146 first undergoes an intermolecular carbopalladation of the double bond in the added norbornene 116, and only then follows an intramolecular carbopalladation of the allene moiety in 146 ensuing /3-hydride elimination finally provides the tricyclic compound 147 (Scheme 37)7 ... 

Scheme 37 Two cascade cyclizations involving inter- or intramolecular carbopalladations of allenes.

Alike olefins, allenes also undergo palladium mediated addition in the presence of N-H or O-H bonds. Although these reactions show some similarity to Wacker-type processes, from the mechanistic point of view they are quite different. Allenes, such as the cr-aminoallene in 3.69., usually undergo addition with palladium complexes (e.g. carbopalladation in 3.69. and 3.70., or hydropalladation in 3.71.), which leads to the formation of a functionalized allylpalladium complex. Subsequent intramolecular nucleophilic attack by the amino group leads to the closure of the pyrroline ring.87... 

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... 

Compounds containing cumulated double bonds (e.g. allenes) also undergo Heck coupling with haloazines. 5-Bromopyrimidine was found to react with an acetylallene to give rise to the furylated pyrimidine in near quantitative yield (7.55.)76, Here the carbopalladation takes place on the... 

Quite recently, Grigg and co-workers have based several of their ingenious multicomponent reactions on the combination of the above-mentioned palladium-catalyzed coupling reactions of allenes with a subsequent reaction in a one-pot operation. For example, the catalytic re-allylpalladium species generated from the carbopalladation of the allene with iodobenzene was captured by a phenolic nucle-... 

Ma and co-workers have reported the selective synthesis of pyrrolidine derivatives through a three-component reaction based on a conceptually related strategy (Scheme 8.29) [72], Beginning with the catalytic intermolecular carbopalladation of y-allenic malonate 57 in the presence of a base, they succeeded in intercepting the internal carbonucleophile 58 with an imine such as the N-benzylidene p-toluenesulfonamide 59. The attack of the newly formed heteronucleophile on the 7r-allyl palladium intermediate affords the functionalized pyrrolidine 60 with high... 

The aminopalladation and subsequent carbonylation proceed smoothly. The aminopalladation of one of the double bonds of allene 129 generates 130, and CO insertion affords the ester 131 [96]. The carbopalladation of the optically active N-vinyl carbamate 132 with malonate afforded 133. Then CO insertion and trapping with vinylstannane produced the ketone 134 with 95% de, which was converted to 135 [97]. 

A mechanistic rationale for the Pd-catalyzed addition of a C-H bond at nitriles to allenes is outlined in Scheme 3. The oxidative insertion of Pd(0) into the C-H bond of nitrile 1 produces the Pd(II) hydride species 16 (or alternatively a tautomeric structure E E2C=C=N PdH Ln may be more suitable, where E = H, alkyl, aryl and/or EWG). Carbopalladation of the allene 2 would afford the alkenylpalladium complex 17 (carbopalladation mechanism), which would undergo reductive coupling to give the addition product 3 and regenerates Pd(0) species. As an alternative mechanism, it may be considered that the hydropalladation of allenes with the Pd(II) intermediate 16 gives the jr-allylpalladium complex 18 which undergoes reductive coupling to afford the adduct 3 and a Pd(0) species (hydropalladation mechanism). 

Scheme 3. C-H transformation to allenes hydropalladation or carbopalladation mechanism.

Ma S (2002) Carbopalladation of Allenes. In Negishi E, de Meijere A (eds) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley, New York, p 1491... 

The same authors also reported on palladium-catalyzed domino cycli-zation-anion capture reactions employing allene (69) as a relay switch (Scheme 10) [52], Such a reaction of the alkynyl-tethered aryl iodide 68 starts with an oxidative addition to the catalytic metal species, and is followed by an intramolecular carbopalladation of the triple bond. An intermolecular car-... 

The same palladium-catalyzed domino cyclization-anion capture sequence involving carbopalladation of allene (69), which was employed by Grigg et al. for the synthesis of diene 70 (Scheme 10) can yield 1,3,5-hexatriene 194, when starting from 2-bromo-l-ene-6-yne 193 instead of the aryl iodide 68 (Scheme 32) [52], Under the conditions of its formation, 194 immediately undergoes thermal 67r-electrocyclization to give the bicyclic product 195. 

Based upon the studies on the mechanism of the Cl sequence we rationalized that the elusive allenol intermediate 19 (Chap. 2.2) could participate in intramolecular trapping reactions as an allenyl ether. Furthermore, vinyl allenes are perfectly suited as dienes in Diels-Alder reactions. Considering both reactive functionalities, allenyl ethers and vinyl allenes, which are perfectly suited for domino processes, we designed an insertion sequence based upon cyclizing carbopalladation [76], where the vinyl aUene results from an isomerization of an alkynylation of a vinyl... 

---