Synthesis of Functionalized Isoindoles by the Rhodium-Catalyzed Reaction of Cyanoformates with ortho-Borylbenzalacetone Derivatives

We recently reported the synthesis of α-keto esters by the rhodium-catalyzed reaction of cyanoformates with arylboronic acids. An intermediary organorhodium species undergoes 1,2-addition regioselectively onto the cyano group of cyanoformate and a resultant iminorhodium species is hydrolyzed to a carbonyl group with loss of the nitrogen atom. This unique reactivity of organorhodium species towards the activated cyano group stands in contrast to the reactivities of arylmagnesium bromide and aryllithium species that attack the ester group of cyano-formates in preference to the cyano group. We next envisaged that it would increase the synthetic utility of the unique reactivity of organorhodium species toward cyano groups if the nitrogen atom of the cyano group could be retained in a reaction product. Thus, the application to the synthesis of aza heterocyclic compounds was next attempted. In this communication, we describe the synthesis of isoindoles by the rhodium-catalyzed reaction of cyanoformate with ortho-borylbenzalacetone derivatives. The nitrogen atom of the cyano group is incorporated in the produced isoindole skeleton