New synthetic methodology for construction of the 3,4-dihydroisoquinolinone skeleton: A key structure for isoquinoline alkaloids

We hereby report a new method for preparation of 3,4-dihydroisoquinolin-1(2H)-one as well as isoquinolin-1(2H)-one skeleton starting from the methyl 2-(3-methoxy-3-oxopropyl)benzoate. The ester functionality, adjacent to the methylene, was regiospecifically converted to the desired acyl azide. The isocyanate was transformed into the monoisocyanate by Curtius rearrangement followed by trapping with aniline. The formed urea derivative was cyclized with NaH to give a 3,4-dihydroisoquinolin-1(2H)-one derivative. Incorporation of a double bond into the six-membered ring followed by removal of the substituent resulted in the formation of isoquinolin-1(2H)-one skeleton.

A new synthetic methodology for the construction of N-substituted 3,4-dihydroisoquinolin-1-(2H)-one derivatives was developed starting from methyl 2-(3-methoxy-3-oxopropyl)benzoate.Highlights► A new synthetic method was developed for construction of dihydroisoquinolinone skeletone. ► One of the ester functionalities in methyl 2-(3-methoxy-3-oxopropyl)benzoate was hydrolyzed regiospecifically. ► The acid group was transformed into a urea derivative. ► The urea was cyclized to dihydroisoquinolinone derivative.