Transformations Involving CO Insertion into Aryl or Alkenyl Pd-Carbon Bonds

Transformations Involving CO Insertion into Aryl or Alkenyl Pd-Carbon Bonds 

Palladium-catalyzed carbonyiative reactions of aryl or alkenyl bromides bearing pendant nitrogen nucleophiles have been studied for over 30 years, and have proven useful for the construction of a variety of different heterocyclic compounds [96]. For example, treatment of 140 with catalytic amounts of Pd(OAc)2 and PPha in the presence of BU3N under an atmosphere of CO afforded lactam 141 in 65% yield (Eq. (1.56)) [96a]. This transformation presumably occurs via oxidative addition of the aryl bromide to Pd to provide 142, which undergoes insertion of CO into the Pd—C bond to yield 143. Intramolecular capture of the acylpaUadium intermediate 143 by the tethered amine gives the desired heterocyclic product 

The insertion of CO into Pd-carbon bonds has also been employed in several tandem/cascade reactions that afford five-membered nitrogen heterocycles [97]. A representative example of this approach to the construction of heterocydes involves synthesis of isoindolinones via the Pd-catalyzed coupling of 2-bromobenzaldehyde with two equivalents of a primary amine under an atmosphere of CO [97bj. As shown below (Eq. (1.57)), this method was used for the preparation of 144 in 64% yield. The mechanism of this reaction is likely via initial, reversible condensation of 2-bromobenzaldehyde with 2 equiv of the amine to form an aminal 145. Oxidative addition of the aryl bromide to Pd° followed by CO insertion provides the acylpalladium spedes 146, which is then captured by the pendant aminal to afford the observed product. An alternative mechanism involving intramolecular imine insertion into the Pd—C bond of a related acylpalladium species, followed by formation of a paUadium-amido complex and C—N bond-forming reductive elimination has also been proposed [97b], 

A sequence involving intermolecular Pd-catalyzed carbonylative amidation followed by intramolecular Michael addition has been employed for the construction of isoindolin-l-ones [97dj. For example, treatment of 147 with 4-methoxyaniline under standard conditions for Pd-catalyzed carbonylative coupling gave isoindolinone 

148 in 79% yield (Eq. (1.58)). This transfomiation is effective with a wide array of primary aliphatic and aromatic amine nucleophiles. 

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