Jt-allylpalladium species

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. 

Three-component assembly of allenes, organic halides and arylboronic acids has been reported in which Suzuki coupling of a Jt-allylpalladium complex with an orga-noboronic acid is utilized (Scheme 16.26) [31], Addition of phosphorus ligands to the reaction mixture greatly decreases either the product yields or E/Z ratios. The decrease in E/Z ratio may be explained based on the fact that donor ligands readily promote anti-syn rearrangement of a Jt-allylpalladium species via a cr-allylpalladium intermediate. 

Facing all the mechanism-related peculiarities of the thermally induced rearrangement it was consequential to try to shift the reaction toward one end of the mechanistic spectrum. The first steps in that direction were undertaken by Hiroi et ah in 1984 they reported on a palladium-catalyzed variant of the reaction [49]. With enantiomerically enriched sulfinates 61 (Scheme 16) they found a much faster reaction as compared to the uncatalyzed one, allowing a reduction of the reaction temperature down to - 78 °C ( ). The stereospecificity of the rearrangement depended heavily on the substitution pattern (between 28 and 92%) and was traced back to the intermediacy of a configurationally stable ri -jt-allylpalladium species whose configuration was influenced by the S centro chirality. Unfortunately, due to difficulties in the preparation of enantiomerically pure 2-alkenylsulfinates (see above), the ee values of the resulting allylic sulfones were quite low. 

In 2001, Gai et al. developed a palladium-catalyzed three-component cascade reaction for the synthesis of bis(2-arylallyl) tertiary amines from aryl iodides, allene, and primary amines [103] (Scheme 6.77). Aryl iodides react with allene to form a Jt-allylpalladium species 298 which is attacked by primary amines to obtain substituted allyl amines 299. The second nucleophilic attack of Jt-allylpalladium species 298 by amine 299 generates tertiary amines 297. Imines or other carbon nucleophiles can be introduced to this cascade reaction instead of primary amines, which is reported by the same group [104]. 

The proposed mechanism involves the usual oxidative addition of the aryl halide to the Pd(0) complex affording a Pd(II) intermediate (Ar-Pd-Hal), subsequent coordination of allene 8 and migratory insertion of the allene into the Pd-C bond to form the jt-allylpalladium(II) species 123. A remarkable C-C bond cleavage of 123 leads by decarbopalladation to 1,3-diene 120 and a-hydroxyalkylpalladium species 124. /8-H elimination of 124 affords aldehyde 121 and the H-Pd-Hal species, which delivers Pd(0) again by reaction with base (Scheme 14.29). The originally expected cyclization of intermediate 123 by employment of the internal nucleophilic hydroxyl group to form a pyran derivative 122 was observed in a single case only (Scheme 14.29). 

The reaction was further applied to the synthesis of spiro heterocycles (Scheme 16.4) [8], The oxidative addition of an iodide to a Pd(0) species generates an ArPdl species, into which an internal olefin inserts to form an alkylpalladium complex otherwise difficult to access. Allene participates in the reaction at this stage to provide a jt-allylpalladium complex, which is attacked by the amine intramolecularly to afford the procuct. 

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. 

First, oxidative addition of 2-iodophenol to a Pd(0) species gives rise to an arylpal-ladium complex, which in turn undergoes carbonylation followed by insertion of allene to generate a 2-acyl-jt-allylpalladium complex. Attack by an internal hydroxyl group gives an a-exo-methylene ketone (Scheme 16.11). 

An a-allenic sulfonamide undergoes Pd-catalyzed carbonylative cyclization with iodobenzene, affording a mixture of isomeric heterocycles (Scheme 16.12) [17]. The coupling reaction of an allene with a PhCOPdl species takes place at the allenyl central catrbon to form a 2-acyl-Jt-allylpalladium complex, which is attacked by an internal sulfonamide group in an endo mode, affording a mixture of isomeric heterocycles (Scheme 16.13). 

Synthetically useful allylstannanes are provided by palladium-catalyzed carbostan-nylation using hexamethylditin (Scheme 16.58) [63]. The reaction mechanism can be rationalized by transmetallation between ditin and a Jt-allylpalladium complex produced by reaction of an allene with an arylpalladium iodide. In this process, hexamethylditin is added to the reaction mixture slowly via a syringe pump to suppress its high reactivity towards the arylpalladium species leading to an arylstannane. 

A bromoallene was demonstrated to act as an allyl dication equivalent. When treated with Pd(0) in an alcoholic solvent, an ei-hydroxybromoallene provides a mediumsized heterocycle (Scheme 16.101) [106]. The oxidative addition of a bromoallene to Pd(0) generates an allenylpalladium species, which is successively transformed into a Jt-allylpalladium complex through the attack of the hydroxyl group on the sp carbon followed by the protonation of the resulting Pd-carbene complex. Finally, the products are provided as a mixture of regioisomers by the nucleophilic attack of the external methanol. 

The Pd-catalyzed hydrocarbonations of methyleneaziridines 14 do not proceed through the formation of a Jt-allylpalladium intermediates, instead via a chelation effect. The hydropalladation of methyleneaziridines with the Pd(II) hydride species 16, followed by reductive elimination gives the non-ring-opened products 15. It is noteworthy to mention that the palladium-catalyzed intermolecular or intramolecular addition of nitriles to carbon-carbon multiple bonds can be explained by the hydropalladation mechanism, except for the intramolecular addition to the C=C triple bond of alkynes (vide infra). 

Substitution reactions of allylic substrates with nucleophiles have been shown to be catalyzed by certain palladium complexes [2, 42], The catalytic cycle of the reactions involves Jt-allylpalladium as a key intermediate (Scheme 2-22). Oxidative addition of the allylic substrate to a palladium(o) species forms a rr-allylpal-ladium(n) complex, which undergoes attack of a nucleophile on the rr-allyl moiety to give an allylic substitution product. The substitution reactions proceed in an Sn or Sn- manner depending on catalysts, nucleophiles, and substituents on the substrates. Studies on the stereochemistry of the allylic substitution have revealed that soft carbon nucleophiles represented by sodium dimethyl malonate attack the TT-allyl carbon directly from the side opposite to the palladium (Scheme 2-23). 

Scheme 3-54). This transformation constitutes a cascade of an intramolecular Heck insertion and subsequent heterocyclization. The initially formed arylpalladium species attacks the bridgehead position of the diene functionality in 238 to foim a JT-allylpalladium complex which is trapped by the internal nucleophilic phenol moiety (cf. Scheme 3-26). Since the starting diene 238 can be prepared in both enantiomeric forms by asymmetric reduction of a ketone, this sequence allows the preparation of both the natural morphine and its unnatural enantiomer. 

This reaction constitutes a special type of process in which a hydrogen and a nucleophile are added across the diene, with formation of a carbon-hydrogen bond in the 1-position and a carbon-Nu bond in the 4-position. Some examples of such reactions are hydrosilylation [12-18], hydrostannation [19,20], hydroamination [21, 22], and addition of active methylene compounds [21a, 23, 24]. These reactions are initiated by an oxidative addition of H-Nu to the palladium(O) catalyst, which produces a palladium hydride species 1 in which the nucleophile is coordinated to the metal (Scheme 11.1). The mechanism commonly accepted for these reactions involves insertion of the double bond into the palladium-hydride bond (hydride addition to the diene), which gives a JT-allylpalladium intermediate. Now, depending... 

With the assistance of palladium(II) complexes such as PdCl2(CH3CN)2, allenes are capable of undergoing intramolecular addition of a nucleophilic functional group connected to the a-carbon. This intramolecular reaction is known to proceed mainly by palladation at the central carbon to generate alkenylpaUadium species (eq 25, path a), which undergoes further reactions. Alternatively, a jT-allylpalladium is formed if the nucleophile attacks the central carbon (path b). 

In 2009, Kemmerer et al. uncovered a phosphine-free carbopalladation/allylic alkylation cascade sequence for the synthesis of 4-(a-styryl) y-lactams 308 [106] (Scheme 6.79). The reaction pathway of this transformation involves the formation of Jt-allylpalladium(n) species 307, which was trapped by the intermolecular active methylene. Both electron-rich and electron-deficient aryl iodides could be introduced efficiently to this cascade process. Li and Dixon developed a stereoselective and efficient protocol for the synthesis of spirolactam 310 employing a similar carbopalladation/jt-allylpalladium trapping strategy [107] (Scheme 6.80). 

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