Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1( 2H)-ones

Beilstein J Org Chem. 2020 May 20;16:1084-1091. doi: 10.3762/bjoc.16.95. eCollection 2020.

Abstract

Cascade cyclocarbopalladation of the readily available aryl/alkyl-substituted propargylic amides containing an aryl iodide moiety, followed by Suzuki-Miyaura coupling with arylboronic acids, allowed an efficient regio- and stereoselective synthesis of tetrasubstituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones. Moreover, cascade cyclocarbopalladation, followed by the reaction with 2-alkynyltrifluoroacetanilides, accomplished a double cyclization to afford challenging 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones bearing a 3-indolyl substituent through aminopalladation/reductive elimination.

Keywords: alkynylanilines; arylboronic acids; indoles; isoquinolinones; palladium.

Grant support

We gratefully acknowledge the University of L’Aquila for financial support.