Palladium-catalyzed tandem Heck/carbonylation/aminocarbonylation en route to chiral heterocyclic α-ketoamides

An unprecedented tandem carbonylation/aminocarbonylation triggered by palladium-catalyzed enantioselective Heck-type exocyclopalladation delivering chiral heterocyclic alpha-ketoamides has been developed. The uncommon double CO insertion into the sigma-alkylpalladium intermediate takes place selectively under atmospheric pressure of CO using alkylamine as the nucleophile. Unique structures hybridizing alkyl alpha-ketoamides with indolin-2-one containing a C3 all-carbon quaternary stereogenic center and 5,7-dihydro-6H-dibenzo[b,d]azepin-6-one containing a thermodynamically stabilized stereogenic biaryl axis are produced in good yields with excellent enantio- and/or diastereoselectivities.

Automated summary

An unprecedented tandem carbonylation/aminocarbonylation reaction triggered by a palladium-catalyzed enantioselective Heck-type exocyclopalladation has been developed to deliver chiral heterocyclic alpha-ketoamides. Unique structures featuring alkyl alpha-ketoamides hybridized with indolin-2-one and 5,7-dihydro-6H-dibenzo[b,d]azepin-6-one, containing stereogenic centers, are produced in good yields with excellent enantio- and/or diastereoselectivities.