Rapid Access to Multisubstituted Acrylamides from Cyclic Ketones via Palladium/Norbornene Cooperative Catalysis

Abstract

A strategy to access diverse multisubstituted acrylamides from cyclic ketones is realized via palladium/norbornene-catalyzed α-carbamoylation and ipso-functionalization of the corresponding enol triflates. The development of bulky C2 secondary amide-substituted norbornene cocatalysts is the key to achieve the desired reactivity and selectivity. Readily available carbamoyl chlorides serve as effective electrophiles; various moieties including alkenyl, hydrogen, alkynyl, aryl, and alkyl groups can be installed at the ipso position. In addition, tandem α-carbamoylation/ipso-annulations are demonstrated to furnish lactam-containing polycyclic scaffolds. The utility of this method is exemplified in the streamlined preparation of a platelet-activating factor (PAF)-antagonist.